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Phase Ib/II Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02807844
Collaborator
(none)
141
Enrollment
20
Locations
10
Arms
47.2
Actual Duration (Months)
7.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study of MCS110 with PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the combination of MCS110 with PDR001 in adult patients with solid tumors.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Combined treatment with MCS110 and PDR001 was expected to result in Tumor-associated macrophages (TAM) depletion, enhanced T-cell activation and synergistic antitumor activity in the clinical setting.

This study was a Phase Ib/II, multi-center, open label study starting with a Phase Ib dose escalation part followed by a Phase II part. MCS110 and PDR001 were administered i.v. Q3W until the patient experienced unacceptable toxicity, progressive disease as per irRC and/or treatment was discontinued at the discretion of the investigator or the patient. Patients were not to discontinue treatment based on progressive disease per Response evaluation criteria in solid tumors (RECIST) v1.1. During the Phase Ib part of the study, cohorts of patients were treated with increasing doses of MCS110 and PDR001 every 3 weeks until a Recommended Phase 2 Dose (RP2D) was determined for this treatment combination.

To assure that the combination RP2D did not exceed the Maximum tolerated dose (MTD), the combination MCS110 and PDR001 dose escalation was guided by a Bayesian logistic regression model (BLRM) with overdose control (EWOC) principle based on dose limiting toxicity data in the context of available safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) information. Once the MTD and/or RP2D was declared, additional patients were enrolled in the Phase II part in order to assess the preliminary anti-tumor activity of MCS110 in combination with PDR001 in anti-PD1/PD-L1-naive triple negative breast cancer (TNBC), pancreatic (PC), endometrial carcinoma (EC) and anti PD1/PD-L1-resistance melanoma (ME).

Study Design

Study Type:
Interventional
Actual Enrollment :
141 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II, Open Label, Multicenter Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies
Actual Study Start Date :
Jun 29, 2016
Actual Primary Completion Date :
Jun 4, 2020
Actual Study Completion Date :
Jun 4, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W

Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W

Drug: MCS110
MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W

    Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W

    Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W

    Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W

    Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W

    Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC

    Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC)

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC

    Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC)

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC

    Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC)

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Experimental: Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME

    Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)

    Drug: MCS110
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
    Other Names:
  • colony-stimulating factor-1 [CSF-1])

    • Drug: PDR001
    MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

    Outcome Measures

    Primary Outcome Measures

    1. Phase Ib: Percentage of Participants With Adverse Events, as a Measure of Safety [From start of treatment to a maximum timeframe of 116.4 weeks for phase Ib]

      Phase Ib: To characterize the safety and tolerability of MCS110 in combination with PDR001 in patients with advanced solid malignancies and to identify a recommended dose combination for Phase II.

    2. Phase II : Overall Response Rate (ORR) - Per RECIST v1.1 [4 years]

      Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)

    3. Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per RECIST v1.1 - Mean [4 years]

      Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) - mean (FAS)

    4. Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per RECIST v1.1 [4 years]

      Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1

    5. Phase II: Bayesian Inference of Clinical Benefit Rate - Per RECIST v1.1- Mean [4 years]

      Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1

    6. Phase Ib: Planned Dose Intensity - MCS110 [Measured up to a max of 112.4 weeks]

      To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for MCS110 is cumulative planned dose (mg/kg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).

    7. Phase Ib: Relative Dose Intensity - MCS110 [Measured up to a max of 112.4 weeks]

      To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/kg/3wks)/planned dose intensity (mg/kg/3wks).

    8. Phase Ib: Planned Dose Intensity - PDR001 [Measured up to a max of 112.4 weeks]

      To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for PDR001 (mg/3wks) is planned cumulative dose (mg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).

    9. Phase Ib: Relative Dose Intensity - PDR001 [Measured up to a max of 112.4 weeks]

      To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/3wks)/planned dose intensity (mg/3wks).

    10. Phase Ib: Number of Participants With Dose Reductions [Measured up to a max of 112.4 weeks]

      To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.

    11. Phase Ib: Number of Dose Interruptions Per Participant [Measured up to a max of 112.4 weeks]

      To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.

    12. Phase Ib: Number of Subjects With at Least One Dose Interruption [Measured up to a max of 112.4 weeks]

      To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.

    13. Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) During the First 2 Cycles of Study Treatment [the first 2 cycles of study treatment; cycle = 21 days (i.e., at day 42)]

      Phase Ib: Dose limiting toxicities occurring during the first 2 cycles by system organ class, preferred term and maximum grade for Phase Ib. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 was used for all grading.

    Secondary Outcome Measures

    1. Phase II : Overall Response Rate (ORR) - Per irRC [4 years]

      Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC) (FAS)

    2. Phase Ib: Overall Response Rate (ORR) [4 years]

      Phase Ib: Overall Response Rate (Complete response (CR) or Partial response (PR)), per RECIST v1.1 and per immune related Response criteria (irRC)

    3. Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per irRC - Mean [4 years]

      Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC)- mean (FAS)

    4. Phase 1b: Clinical Benefit Rate (CBR) [4 years]

      Phase 1b: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)

    5. Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per irRC [4 years]

      Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per immune related Response criteria (irRC)

    6. Phase II: Bayesian Inference of Clinical Benefit Rate - Per irRC - Mean [4 years]

      Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on immune related Response criteria (irRC)- mean (FAS)

    7. Phase 1b and Phase II: Progression Free Survival Based on Investigator Assessment as Per RECIST v1.1 and Per Immune Related Response Criteria (irRC) - Using Kaplan-Meier Method - Median [Up to year 4]

      Phase 1b and Phase II: Progression Free Survival. Progression is defined as a 20% increase in the sum of diameter of measurable lesions taking as reference the smallest sum of diameter recorded at or after baseline, or worsening of non-measurable lesions or the appearance of new lesions, using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or Per Immune Related Response Criteria (irRC). Unlike RECIST 1.1, PD per irRC requires confirmation at a new assessment after at least 4 weeks - using Kaplan-Meier method - Median.

    8. Phase 1b and Phase II: Overall Survival - Using Kaplan-Meier Method - Median [Up to year 4]

      Phase 1b and Phase II: Overall Survival - using Kaplan-Meier method - Median

    9. Phase 1b and Phase II: Duration of Response (DOR) [4 years]

      Phase 1b and Phase II: Duration of Response (DOR) per RECIST v1.1 and per immune related Response criteria (irRC)

    10. Phase 1b and Phase II: Disease Control Rate (DCR) [4 years]

      Phase 1b and Phase II: Disease Control Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)

    11. Phase II: Percentage of Participants With Adverse Events, as a Measure of Safety [From start of treatment to a maximum timeframe of 92.4 weeks for phase II.]

      Phase II: To further characterize the safety and tolerability of MCS110 given in combination with PDR001

    12. Phase Ib and Phase II: Immunogenicity MCS110 [4 years]

      Phase Ib and Phase II: Presence of anti-MCS110 antibodies

    13. Phase Ib and Phase II: Immunogenicity PDR001 [4 years]

      Phase Ib and Phase II: Presence of anti-PDR001 antibodies

    14. Phase Ib and Phase II: Pharmacokinetics of MCS110 - AUClast and AUCinf [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) - MCS110

    15. Phase Ib and Phase II: Pharmacokinetics of PDR001 - AUClast and AUCinf [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: Pharmacokinetics (PK) Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) and AUCinf - PDR001

    16. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Cmax and Clast [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - MCS110

    17. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Cmax and Clast [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - PDR001

    18. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Tmax [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - MCS110

    19. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Tmax [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - PDR001

    20. Phase Ib and Phase II: Pharmacokinetics of MCS110 - T1/2 [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - MCS110

    21. Phase Ib and Phase II: Pharmacokinetics of PDR001 - T1/2 [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - PDR001

    22. Phase Ib and Phase II: Pharmacokinetics of MCS110 - CL [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - MCS110

    23. Phase Ib and Phase II: Pharmacokinetics of PDR001 - CL [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - PDR001

    24. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Vz [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - MCS110

    25. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Vz [cycle 1 (day 21) and cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - PDR001

    26. Phase Ib and Phase II: Pharmacokinetics of MCS110 - Accumulation Ratio (AR) [cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - MCS110

    27. Phase Ib and Phase II: Pharmacokinetics of PDR001 - Accumulation Ratio (AR) [cycle 4 (day 84)]

      Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - PDR001

    28. Phase Ib and Phase II: All Collected Deaths [For ontreatment deaths: up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II. For total deaths: up to 3.8 years]

      On treatment deaths are reported from the start of treatment until end of study treatment plus 30 days, up to maximum duration of 116.4 weeks for phase Ib and 92.4 weeks for phase II. Deaths post treatment survival follow up are reported after the on-treatment period, up to a maximum timeframe of 46 months (3.8 years).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Main Inclusion Criteria:

    • Signed informed consent prior to any procedures

    • Phase Ib part: Adult patients with advanced melanoma, endometrial carcinoma, pancreatic or TNBC, with measurable or non-measurable disease who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.

    • Phase II part: Adult patients with advanced solid tumors who have received standard therapy (no more than 3 prior lines of treatment) or are intolerant of standard therapy, have progressed following their last prior therapy, and fit into one of the following groups:

    • Group 1: TNBC who did not receive prior anti-PD-1/PD-L1 treatment

    • Group 2: Pancreatic adenocarcinoma who did not receive prior anti-PD-1/PD-L1 treatment

    • Group 3: Endometrial carcinoma who did not receive prior anti-PD-1/PD-L1 treatment

    • Group 4: Melanoma who progressed on prior anti-PD-1/PD-L1 treatment.

    Main Exclusion Criteria:

    • Patients with the following:

    • Symptomatic central nervous system (CNS) metastases or those requiring local CNS-directed therapy.

    • Abnormal liver, renal, or blood lab values.

    • Impaired cardiac function or clinically significant cardiac disease.

    • Active autoimmune disease or documented autoimmune disease within 3 years of screening.

    • Active infection requiring antibiotic therapy.

    • Known HIV, active hepatitis B or C virus.

    • Concurrent malignant disease.

    • Patients who received systemic anticancer therapy, major surgery, or radiotherapy within 2 weeks of study treatment, or live vaccines within 4 weeks of study treatment.

    • Patients requiring chronic treatment with systemic steroid therapy or any immunosuppressive therapy.

    • Patients who used hematopoietic colony-stimulating growth factors within 2 weeks of study treatment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dana Farber Cancer Center Boston Massachusetts United States 02215
    2 Washington University School of Medicine Saint Louis Missouri United States 63123
    3 The West Clinic Germantown Tennessee United States 38138
    4 MD Anderson Cancer Center Houston Texas United States 77030
    5 Novartis Investigative Site Wilrijk Belgium 2610
    6 Novartis Investigative Site HUS Finland FIN-00029
    7 Novartis Investigative Site Saint Herblain cedex France 44805
    8 Novartis Investigative Site Frankfurt Germany 60590
    9 Novartis Investigative Site Ulm Germany 89081
    10 Novartis Investigative Site Hong Kong Hong Kong
    11 Novartis Investigative Site Milano MI Italy 20133
    12 Novartis Investigative Site Milano MI Italy 20141
    13 Novartis Investigative Site Koto ku Tokyo Japan 135 8550
    14 Novartis Investigative Site Seoul Korea, Republic of 03080
    15 Novartis Investigative Site Seoul Korea, Republic of 05505
    16 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46010
    17 Novartis Investigative Site Madrid Spain 28009
    18 Novartis Investigative Site Chur Switzerland 7000
    19 Novartis Investigative Site Geneve 14 Switzerland CH 1211
    20 Novartis Investigative Site Zuerich Switzerland 8091

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02807844
    Other Study ID Numbers:
    • CMCS110Z2102
    • 2016-000210-29
    First Posted:
    Jun 21, 2016
    Last Update Posted:
    Aug 11, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Triple negative breast cancer
    Pancreatic carcinoma
    Melanoma
    Endometrial Carcinoma
    Immuno oncology
    Monoclonal antibody
    PDR001
    MCS110
    Advanced malignancies
    metasteses
    advanced cancer
    malignant
    Additional relevant MeSH terms:
    Carcinoma
    Melanoma
    Neoplasms
    Triple Negative Breast Neoplasms
    Endometrial Neoplasms
    Pancreatic Neoplasms
    Spartalizumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Period Title: Overall Study
    STARTED 6 12 12 13 6 11 20 20 21 20
    COMPLETED 0 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 6 12 12 13 6 11 20 20 21 20

    Baseline Characteristics

    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME Total
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME) Total of all reporting groups
    Overall Participants 6 12 12 13 6 11 20 20 21 20 141
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    50%
    9
    75%
    8
    66.7%
    10
    76.9%
    5
    83.3%
    8
    72.7%
    20
    100%
    11
    55%
    9
    42.9%
    12
    60%
    95
    67.4%
    >=65 years
    3
    50%
    3
    25%
    4
    33.3%
    3
    23.1%
    1
    16.7%
    3
    27.3%
    0
    0%
    9
    45%
    12
    57.1%
    8
    40%
    46
    32.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.3
    (14.72)
    56.9
    (11.13)
    59.3
    (9.94)
    55.4
    (10.03)
    57.3
    (14.02)
    58.6
    (11.13)
    50.0
    (8.29)
    61.5
    (11.33)
    62.8
    (10.13)
    60.7
    (13.15)
    58.5
    (11.50)
    Sex: Female, Male (Count of Participants)
    Female
    4
    66.7%
    10
    83.3%
    6
    50%
    8
    61.5%
    4
    66.7%
    6
    54.5%
    20
    100%
    8
    40%
    21
    100%
    9
    45%
    96
    68.1%
    Male
    2
    33.3%
    2
    16.7%
    6
    50%
    5
    38.5%
    2
    33.3%
    5
    45.5%
    0
    0%
    12
    60%
    0
    0%
    11
    55%
    45
    31.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    1
    8.3%
    2
    15.4%
    1
    16.7%
    2
    18.2%
    5
    25%
    4
    20%
    4
    19%
    7
    35%
    26
    18.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    0
    0%
    0
    0%
    1
    0.7%
    White
    5
    83.3%
    12
    100%
    10
    83.3%
    11
    84.6%
    5
    83.3%
    9
    81.8%
    14
    70%
    14
    70%
    14
    66.7%
    12
    60%
    106
    75.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    0
    0%
    1
    0.7%
    Unknown or Not Reported
    1
    16.7%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    1
    5%
    2
    9.5%
    1
    5%
    7
    5%

    Outcome Measures

    1. Primary Outcome
    Title Phase Ib: Percentage of Participants With Adverse Events, as a Measure of Safety
    Description Phase Ib: To characterize the safety and tolerability of MCS110 in combination with PDR001 in patients with advanced solid malignancies and to identify a recommended dose combination for Phase II.
    Time Frame From start of treatment to a maximum timeframe of 116.4 weeks for phase Ib

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Adverse events (AEs) - all grades
    6
    100%
    12
    100%
    12
    100%
    13
    100%
    6
    100%
    11
    100%
    Adverse events - Treatment-related - all grades
    6
    100%
    12
    100%
    11
    91.7%
    8
    61.5%
    6
    100%
    8
    72.7%
    Serious Adverse Events (SAEs) - all grades
    3
    50%
    4
    33.3%
    4
    33.3%
    7
    53.8%
    2
    33.3%
    5
    45.5%
    SAEs - Treatment-related - all grades
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    2
    33.3%
    1
    9.1%
    Fatal SAEs - all grades
    0
    0%
    0
    0%
    0
    0%
    2
    15.4%
    0
    0%
    0
    0%
    Fatal SAEs - Treatment-related - all grades
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    AEs leading to discontinuation - all grades
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    1
    9.1%
    AEs leading to discontinuation - Treatment-related - all grades
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    1
    9.1%
    AEs leading to dose adjustment / interruption - all grades
    4
    66.7%
    4
    33.3%
    4
    33.3%
    2
    15.4%
    2
    33.3%
    6
    54.5%
    AEs requiring additional therapy - all grades
    6
    100%
    12
    100%
    10
    83.3%
    12
    92.3%
    4
    66.7%
    10
    90.9%
    2. Primary Outcome
    Title Phase II : Overall Response Rate (ORR) - Per RECIST v1.1
    Description Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Number (90% Confidence Interval) [Percentage of participants]
    5
    83.3%
    0
    0%
    9.5
    79.2%
    0
    0%
    3. Primary Outcome
    Title Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per RECIST v1.1 - Mean
    Description Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) - mean (FAS)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Since objective responses are rare in advanced pancreatic cancer and that long lasting stable disease is considered beneficial to patients, clinical benefit rate (confirmed objective response or SD>4 months) was used as the primary endpoint for antitumor activity in this study changed from objective response to for this patient population.
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Mean (90% Confidence Interval) [Percentage of participants]
    6.7
    111.7%
    NA
    NaN
    10.8
    90%
    0.8
    6.2%
    4. Primary Outcome
    Title Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per RECIST v1.1
    Description Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Number (90% Confidence Interval) [Percentage of participants]
    20
    333.3%
    0
    0%
    9.5
    79.2%
    10.0
    76.9%
    5. Primary Outcome
    Title Phase II: Bayesian Inference of Clinical Benefit Rate - Per RECIST v1.1- Mean
    Description Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Since objective responses are rare in advanced pancreatic cancer and that long lasting stable disease is considered beneficial to patients, clinical benefit rate (confirmed objective response or SD>4 months) was used as the primary endpoint for antitumor activity in this study changed from objective response to for this patient population.
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Mean (90% Confidence Interval) [Percentage of participants]
    NA
    NaN
    0.8
    6.7%
    NA
    NaN
    NA
    NaN
    6. Primary Outcome
    Title Phase Ib: Planned Dose Intensity - MCS110
    Description To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for MCS110 is cumulative planned dose (mg/kg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
    Time Frame Measured up to a max of 112.4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Mean (Standard Deviation) [mg/kg/3wks]
    0.86
    (0.191)
    2.74
    (0.386)
    2.66
    (0.435)
    4.85
    (0.286)
    7.05
    (0.594)
    9.47
    (1.093)
    7. Primary Outcome
    Title Phase Ib: Relative Dose Intensity - MCS110
    Description To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/kg/3wks)/planned dose intensity (mg/kg/3wks).
    Time Frame Measured up to a max of 112.4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Mean (Standard Deviation) [Percentage]
    100
    (100)
    100
    (100)
    100
    (100)
    99.23
    (2.774)
    100
    (100)
    100
    (100)
    8. Primary Outcome
    Title Phase Ib: Planned Dose Intensity - PDR001
    Description To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for PDR001 (mg/3wks) is planned cumulative dose (mg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
    Time Frame Measured up to a max of 112.4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Mean (Standard Deviation) [mg/3wks]
    86.09
    (19.058)
    91.18
    (12.873)
    265.83
    (43.528)
    293.59
    (16.013)
    282.12
    (23.773)
    289.04
    (20.329)
    9. Primary Outcome
    Title Phase Ib: Relative Dose Intensity - PDR001
    Description To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/3wks)/planned dose intensity (mg/3wks).
    Time Frame Measured up to a max of 112.4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Mean (Standard Deviation) [Percentage]
    100.00
    (100.00)
    100.00
    (100.00)
    100.00
    (100.00)
    100.00
    (100.00)
    100.00
    (100.00)
    100.00
    (100.00)
    10. Primary Outcome
    Title Phase Ib: Number of Participants With Dose Reductions
    Description To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
    Time Frame Measured up to a max of 112.4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    n (%) of participants with no dose reduction- Study drug: MCS110
    6
    100%
    12
    100%
    12
    100%
    13
    100%
    6
    100%
    9
    81.8%
    n (%) of participants with no dose reduction- Study drug: PDR001
    6
    100%
    12
    100%
    12
    100%
    13
    100%
    6
    100%
    11
    100%
    11. Primary Outcome
    Title Phase Ib: Number of Dose Interruptions Per Participant
    Description To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
    Time Frame Measured up to a max of 112.4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Number of dose interruptions per subject - Study drug: MCS110
    1.3
    (1.97)
    0.3
    (0.45)
    0.3
    (0.45)
    0.0
    (0.0)
    0.3
    (0.52)
    0.1
    (0.30)
    Number of dose interruptions per subject - Study drug: PDR001
    1.3
    (1.97)
    0.3
    (0.45)
    0.3
    (0.45)
    0.0
    (0.0)
    0.3
    (0.52)
    0.1
    (0.30)
    12. Primary Outcome
    Title Phase Ib: Number of Subjects With at Least One Dose Interruption
    Description To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
    Time Frame Measured up to a max of 112.4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Set. A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Number of subjects with at least one dose interruption - by reason - Adverse Event - MCS110
    3
    50%
    3
    25%
    3
    25%
    0
    0%
    2
    33.3%
    1
    9.1%
    Number of subjects with at least one dose interruption - by reason - Adverse Event - PDR001
    3
    50%
    3
    25%
    3
    25%
    0
    0%
    2
    33.3%
    1
    9.1%
    13. Primary Outcome
    Title Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) During the First 2 Cycles of Study Treatment
    Description Phase Ib: Dose limiting toxicities occurring during the first 2 cycles by system organ class, preferred term and maximum grade for Phase Ib. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 was used for all grading.
    Time Frame the first 2 cycles of study treatment; cycle = 21 days (i.e., at day 42)

    Outcome Measure Data

    Analysis Population Description
    Dose Determination Set (DDS). A statistical analysis for this endpoint was not performed since it is not clinically relevant.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 5 11 9 7 4 4
    n (%) of subjects with at least one event - all grades
    0
    0%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    1
    9.1%
    n (%) Investigations - all grades
    0
    0%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    1
    9.1%
    n (%) Blood creatine phosphokinase increased - all grades
    0
    0%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    1
    9.1%
    14. Secondary Outcome
    Title Phase II : Overall Response Rate (ORR) - Per irRC
    Description Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC) (FAS)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Number (90% Confidence Interval) [Percentage of participants]
    5
    83.3%
    0
    0%
    9.5
    79.2%
    0
    0%
    15. Secondary Outcome
    Title Phase Ib: Overall Response Rate (ORR)
    Description Phase Ib: Overall Response Rate (Complete response (CR) or Partial response (PR)), per RECIST v1.1 and per immune related Response criteria (irRC)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Overall Response Rate as per investigator based on RECIST v1.1
    16.7
    278.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9.1
    82.7%
    Overall Response Rate - as per investigator based on irRC
    16.7
    278.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9.1
    82.7%
    16. Secondary Outcome
    Title Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per irRC - Mean
    Description Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC)- mean (FAS)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Since objective responses are rare in advanced pancreatic cancer and that long lasting stable disease is considered beneficial to patients, clinical benefit rate (confirmed objective response or SD>4 months) was used as the primary endpoint for antitumor activity in this study changed from objective response to for this patient population.
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Mean (90% Confidence Interval) [Percentage of participants]
    6.7
    111.7%
    NA
    NaN
    10.8
    90%
    0.8
    6.2%
    17. Secondary Outcome
    Title Phase 1b: Clinical Benefit Rate (CBR)
    Description Phase 1b: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W
    Measure Participants 6 12 12 13 6 11
    Clinical Benefit Rate - as per investigator based on RECIST v1.1
    33.3
    555%
    8.3
    69.2%
    0
    0%
    0
    0%
    0
    0%
    18.2
    165.5%
    Clinical Benefit Rate - as per investigator based on irRC
    50.0
    833.3%
    8.3
    69.2%
    0
    0%
    7.7
    59.2%
    33.3
    555%
    18.2
    165.5%
    18. Secondary Outcome
    Title Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per irRC
    Description Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per immune related Response criteria (irRC)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Number (90% Confidence Interval) [Percentage of participants]
    20.0
    333.3%
    5.0
    41.7%
    19.0
    158.3%
    30.0
    230.8%
    19. Secondary Outcome
    Title Phase II: Bayesian Inference of Clinical Benefit Rate - Per irRC - Mean
    Description Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on immune related Response criteria (irRC)- mean (FAS)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Since objective responses are rare in advanced pancreatic cancer and that long lasting stable disease is considered beneficial to patients, clinical benefit rate (confirmed objective response or SD>4 months) was used as the primary endpoint for antitumor activity in this study changed from objective response to for this patient population.
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Mean (90% Confidence Interval) [Percentage of participants]
    NA
    NaN
    5.6
    46.7%
    NA
    NaN
    NA
    NaN
    20. Secondary Outcome
    Title Phase 1b and Phase II: Progression Free Survival Based on Investigator Assessment as Per RECIST v1.1 and Per Immune Related Response Criteria (irRC) - Using Kaplan-Meier Method - Median
    Description Phase 1b and Phase II: Progression Free Survival. Progression is defined as a 20% increase in the sum of diameter of measurable lesions taking as reference the smallest sum of diameter recorded at or after baseline, or worsening of non-measurable lesions or the appearance of new lesions, using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or Per Immune Related Response Criteria (irRC). Unlike RECIST 1.1, PD per irRC requires confirmation at a new assessment after at least 4 weeks - using Kaplan-Meier method - Median.
    Time Frame Up to year 4

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 12 12 13 6 11 20 20 21 20
    Median PFS - per RECIST v1.1
    1.5
    1.3
    1.3
    1.1
    1.3
    1.2
    1.6
    1.3
    1.3
    2.4
    Median PFS - per iiRC
    8.2
    2.2
    1.3
    1.0
    1.3
    1.2
    1.6
    1.3
    1.3
    3.7
    21. Secondary Outcome
    Title Phase 1b and Phase II: Overall Survival - Using Kaplan-Meier Method - Median
    Description Phase 1b and Phase II: Overall Survival - using Kaplan-Meier method - Median
    Time Frame Up to year 4

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 12 12 13 6 11 20 20 21 20
    Median (90% Confidence Interval) [months]
    12.3
    9.6
    4.2
    2.8
    22.8
    5.7
    8.9
    2.6
    11.7
    19.7
    22. Secondary Outcome
    Title Phase 1b and Phase II: Duration of Response (DOR)
    Description Phase 1b and Phase II: Duration of Response (DOR) per RECIST v1.1 and per immune related Response criteria (irRC)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 12 12 13 6 11 20 20 21 20
    Duration of response(days) - based on RECIST v1.1
    372.0
    NA
    NA
    NA
    NA
    155.0
    169
    NA
    328.5
    NA
    Duration of response(days) - based on irRC
    372.0
    NA
    NA
    NA
    NA
    155.0
    169
    NA
    328.5
    NA
    23. Secondary Outcome
    Title Phase 1b and Phase II: Disease Control Rate (DCR)
    Description Phase 1b and Phase II: Disease Control Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 12 12 13 6 11 20 20 21 20
    Disease Control Rate - as per investigator based on RECIST v1.1
    33.3
    8.3
    0
    15.4
    16.7
    18.2
    20.0
    0
    19.0
    35.0
    Disease Control Rate as per investigator based on irRC
    50.0
    8.3
    0
    15.4
    33.3
    18.2
    20.0
    5.0
    19.0
    45.0
    24. Secondary Outcome
    Title Phase II: Percentage of Participants With Adverse Events, as a Measure of Safety
    Description Phase II: To further characterize the safety and tolerability of MCS110 given in combination with PDR001
    Time Frame From start of treatment to a maximum timeframe of 92.4 weeks for phase II.

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 20 20 21 20
    Adverse events - all grades
    20
    333.3%
    20
    166.7%
    21
    175%
    20
    153.8%
    Adverse events - Treatment-related - all grades
    16
    266.7%
    15
    125%
    17
    141.7%
    19
    146.2%
    SAEs - all grades
    8
    133.3%
    14
    116.7%
    8
    66.7%
    7
    53.8%
    SAEs - Treatment-related - all grades
    1
    16.7%
    4
    33.3%
    4
    33.3%
    1
    7.7%
    Fatal SAEs - all grades
    1
    16.7%
    1
    8.3%
    0
    0%
    1
    7.7%
    Fatal SAEs - Treatment-related - all grades
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    AEs leading to discontinuation - all grades
    1
    16.7%
    1
    8.3%
    1
    8.3%
    2
    15.4%
    AEs leading to discontinuation - Treatment-related - all grades
    1
    16.7%
    0
    0%
    1
    8.3%
    1
    7.7%
    AEs leading to dose adjustment / interruption - all grades
    11
    183.3%
    4
    33.3%
    8
    66.7%
    11
    84.6%
    AEs requiring additional therapy - all grades
    19
    316.7%
    18
    150%
    19
    158.3%
    17
    130.8%
    25. Secondary Outcome
    Title Phase Ib and Phase II: Immunogenicity MCS110
    Description Phase Ib and Phase II: Presence of anti-MCS110 antibodies
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 12 12 13 6 11 20 20 21 20
    Baseline positive
    0
    0%
    1
    8.3%
    1
    8.3%
    1
    7.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline negative
    6
    100%
    11
    91.7%
    11
    91.7%
    12
    92.3%
    6
    100%
    11
    100%
    19
    95%
    19
    95%
    17
    81%
    18
    90%
    Baseline missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    1
    5%
    4
    19%
    2
    10%
    Baseline positive, on treatment persistent positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline positive, on treatment only last positive
    0
    0%
    0
    0%
    0
    0%
    1
    7.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline positive, on treatment any positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline positive, on treatment all negative
    0
    0%
    1
    8.3%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline negative, on treatment persistent positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline negative, on treatment only last positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline negative, on treatment any positive
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline negative, on treatment all negative
    5
    83.3%
    10
    83.3%
    8
    66.7%
    6
    46.2%
    5
    83.3%
    6
    54.5%
    12
    60%
    16
    80%
    14
    66.7%
    17
    85%
    Baseline missing, on treatment persistent positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline missing, on treatment only last positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline missing, on treatment any positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline missing, on treatment all negative
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    26. Secondary Outcome
    Title Phase Ib and Phase II: Immunogenicity PDR001
    Description Phase Ib and Phase II: Presence of anti-PDR001 antibodies
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 12 12 13 6 11 20 20 21 20
    Baseline positive
    0
    0%
    2
    16.7%
    1
    8.3%
    2
    15.4%
    1
    16.7%
    2
    18.2%
    1
    5%
    1
    5%
    0
    0%
    1
    5%
    Baseline negative
    6
    100%
    10
    83.3%
    11
    91.7%
    10
    76.9%
    5
    83.3%
    8
    72.7%
    18
    90%
    17
    85%
    19
    90.5%
    19
    95%
    Baseline missing
    0
    0%
    0
    0%
    0
    0%
    1
    7.7%
    0
    0%
    1
    9.1%
    1
    5%
    2
    10%
    2
    9.5%
    0
    0%
    Baseline positive, on treatment persistent positive
    0
    0%
    1
    8.3%
    0
    0%
    1
    7.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline positive, on treatment only last positive
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    0
    0%
    0
    0%
    Baseline positive, on treatment any positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    1
    9.1%
    1
    5%
    0
    0%
    0
    0%
    1
    5%
    Baseline positive, on treatment all negative
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline negative, on treatment persistent positive
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    Baseline negative, on treatment only last positive
    1
    16.7%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    4
    20%
    1
    4.8%
    0
    0%
    Baseline negative, on treatment any positive
    1
    16.7%
    3
    25%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    0
    0%
    2
    10%
    Baseline negative, on treatment all negative
    4
    66.7%
    4
    33.3%
    8
    66.7%
    6
    46.2%
    4
    66.7%
    2
    18.2%
    11
    55%
    10
    50%
    16
    76.2%
    13
    65%
    Baseline missing, on treatment persistent positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline missing, on treatment only last positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline missing, on treatment any positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Baseline missing, on treatment all negative
    0
    0%
    0
    0%
    0
    0%
    1
    7.7%
    0
    0%
    1
    9.1%
    1
    5%
    0
    0%
    0
    0%
    1
    5%
    27. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of MCS110 - AUClast and AUCinf
    Description Phase Ib and Phase II: PK Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) - MCS110
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples. There were some patients with AUClast but no AUCinf parameters because AUCinf could not be extrapolated from the data (i.e. the % of AUC extrapolated past the last time point is greater than 20% or the adjusted R squared parameter for the regression fit of the terminal phase of the PK profile is < 0.75).
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    AUClast (day*ng/mL) - cycle 1 - day 21
    46900
    (9080)
    343000
    (142000)
    249000
    (93400)
    490000
    (149000)
    909000
    (233000)
    1090000
    (231000)
    1200000
    (507000)
    1090000
    (352000)
    1120000
    (440000)
    1270000
    (335000)
    AUCinf (day*ng/mL) - cycle 1 - day 21
    50100
    (11600)
    383000
    (178000)
    330000
    (73400)
    560000
    (177000)
    1020000
    (336000)
    988000
    (116000)
    AUClast (day*ng/mL) - cycle 4 - day 84
    41000
    (22800)
    213000
    (92200)
    232000
    (99300)
    710000
    (171000)
    1520000
    (353000)
    1200000
    (1030000)
    1200000
    (389000)
    918000
    (102000)
    1010000
    (337000)
    1240000
    (499000)
    AUCinf (day*ng/mL) - cycle 4 - day 84
    42300
    (21900)
    260000
    (73500)
    253000
    (114000)
    619000
    (NA)
    769000
    (NA)
    28. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of PDR001 - AUClast and AUCinf
    Description Phase Ib and Phase II: Pharmacokinetics (PK) Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) and AUCinf - PDR001
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples. There were some patients with AUClast but no AUCinf parameters because AUCinf could not be extrapolated from the data (i.e. the % of AUC extrapolated past the last time point is greater than 20% or the adjusted R squared parameter for the regression fit of the terminal phase of the PK profile is < 0.75).
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    AUClast (day*ug/mL) - cycle 1 - day 21
    229
    (68.3)
    271
    (53.8)
    651
    (322)
    604
    (309)
    581
    (147)
    450
    (135)
    825
    (402)
    782
    (264)
    764
    (311)
    782
    (307)
    AUCinf (day*ug/mL) - cycle 1 - day 21
    274
    (NA)
    610
    (NA)
    747
    (NA)
    710
    (NA)
    AUClast (day*ug/mL) - cycle 4 - day 84
    369
    (26.4)
    330
    (182)
    1020
    (526)
    2020
    (1170)
    954
    (179)
    718
    (288)
    1170
    (388)
    1330
    (555)
    1660
    (283)
    1260
    (533)
    AUCinf (day*ug/mL) - cycle 4 - day 84
    196
    (NA)
    29. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of MCS110 - Cmax and Clast
    Description Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - MCS110
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    Cmax (ng/mL) - cycle 1 - day 21
    17400
    (1870)
    58800
    (16900)
    56700
    (17800)
    96900
    (28600)
    122000
    (17100)
    186000
    (54000)
    158000
    (44800)
    130000
    (38400)
    134000
    (64900)
    151000
    (42500)
    Clast (ng/mL) - cycle 1 - day 21
    1120
    (795)
    1290
    (2760)
    6600
    (6370)
    9130
    (11500)
    15100
    (9070)
    28700
    (27800)
    33000
    (21300)
    12900
    (10700)
    24500
    (20100)
    17500
    (11400)
    Cmax (ng/mL) -- cycle 4 - day 84
    13500
    (5580)
    53000
    (9790)
    48900
    (14100)
    76400
    (24000)
    176000
    (19800)
    189000
    (29400)
    159000
    (39800)
    152000
    (58000)
    128000
    (42600)
    147000
    (38300)
    Clast (ng/mL) - cycle 4 - day 84
    510
    (457)
    5700
    (10300)
    3490
    (2410)
    7350
    (5870)
    45100
    (12400)
    34100
    (29800)
    57600
    (45000)
    33300
    (42600)
    18600
    (21700)
    29400
    (20700)
    30. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of PDR001 - Cmax and Clast
    Description Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - PDR001
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    Cmax (ug/mL) - cycle 1 - day 21
    24
    (9.52)
    29.5
    (6.56)
    73.4
    (22.3)
    77
    (24.3)
    76.6
    (36.8)
    64.2
    (20.4)
    94.5
    (27.4)
    75.3
    (23.9)
    80.2
    (24)
    70.3
    (21.6)
    Clast (ug/mL) - cycle 1 - day 21
    7.73
    (2.97)
    7.24
    (2.95)
    19.4
    (11.7)
    26.4
    (11.8)
    22.7
    (12.8)
    17.2
    (8.67)
    34.5
    (13.3)
    24
    (12)
    22.8
    (9.44)
    24.4
    (14.6)
    Cmax (ug/mL) -- cycle 4 - day 84
    29.5
    (9.3)
    36.8
    (10.5)
    126
    (54.6)
    153
    (22.6)
    92
    (22.1)
    85.9
    (16.8)
    123
    (56.8)
    127
    (7)
    122
    (23.6)
    108
    (23.4)
    Clast (ug/mL) - cycle 4 - day 84
    10.7
    (2.25)
    14.5
    (8.47)
    65.1
    (37.6)
    71
    (6.65)
    47.5
    (25.7)
    35.6
    (14.7)
    81.4
    (43.6)
    62.1
    (9.93)
    48.8
    (20.6)
    51.3
    (23.7)
    31. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of MCS110 - Tmax
    Description Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - MCS110
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    Tmax (h) - cycle 1 - day 21
    2.02
    1.92
    2.08
    2.13
    2.06
    2.04
    2.01
    2.08
    2.09
    2.08
    Tmax (h) - cycle 4 - day 84
    2
    2.05
    2.03
    13
    2
    2.03
    2
    2.02
    2.04
    2.05
    32. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of PDR001 - Tmax
    Description Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - PDR001
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    Tmax (h) - cycle 1 - day 21
    11.5
    2.08
    1.53
    1.57
    1.53
    1.52
    1.5
    1.5
    1.5
    1.5
    Tmax (h) - cycle 4 - day 84
    1.52
    1.53
    1.2
    1.57
    1.5
    1.45
    1.53
    1.47
    1.54
    1.5
    33. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of MCS110 - T1/2
    Description Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - MCS110
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    T1/2 (day) - cycle 1 - day 21
    1.5
    2.16
    3.3
    3.48
    6.35
    4.36
    T1/2 (day) - cycle 4 - day 84
    1.77
    1.53
    4.08
    6.32
    4.82
    34. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of PDR001 - T1/2
    Description Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - PDR001
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    T1/2 (day) - cycle 1 - day 21
    8.14
    7.71
    7.13
    7.33
    T1/2 (day) - cycle 4 - day 84
    7.81
    35. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of MCS110 - CL
    Description Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - MCS110
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    CL (L/h/kg) - cycle 1 - day 21
    0.000863
    (0.000158)
    0.000388
    (0.000181)
    0.000394
    (0.0000833)
    0.000407
    (0.000131)
    0.000338
    (0.000117)
    0.000427
    (0.0000558)
    CL (L/h/kg) - cycle 4 - day 84
    0.00117
    (0.000549)
    0.000523
    (0.000199)
    0.000315
    (0.000218)
    0.000337
    (NA)
    0.000541
    (NA)
    36. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of PDR001 - CL
    Description Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - PDR001
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    CL (L/h) - cycle 1 - day 21
    0.0152
    (NA)
    0.0205
    (NA)
    0.0167
    (NA)
    0.0176
    (NA)
    CL (L/h) - cycle 4 - day 84
    0.0213
    (NA)
    37. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of MCS110 - Vz
    Description Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - MCS110
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    Vz (L/kg) - cycle 1 - day 21
    0.0486
    (0.00989)
    0.0334
    (0.00783)
    0.0423
    (0.00875)
    0.051
    (0.0206)
    0.0651
    (0.0201)
    0.065
    (0.0267)
    Vz (L/kg) - cycle 4 - day 84
    0.0684
    (0.0407)
    0.0294
    (0.0128)
    0.045
    (0.0308)
    0.0736
    (NA)
    0.0904
    (NA)
    38. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of PDR001 - Vz
    Description Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - PDR001
    Time Frame cycle 1 (day 21) and cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set. Some patients were excluded from the PK parameter analysis because of missed visits, missed sampling, early termination, dosing outside the planned dose, or lost samples.
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 11 12 13 6 11 20 19 20 20
    Vz (L) - cycle 1 - day 21
    4.28
    (NA)
    5.47
    (NA)
    4.13
    (NA)
    4.47
    (NA)
    Vz (L) - cycle 4 - day 84
    5.76
    (NA)
    39. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of MCS110 - Accumulation Ratio (AR)
    Description Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - MCS110
    Time Frame cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 3 6 4 2 3 3 4 3 4 12
    Mean (Standard Deviation) [Ratio of AUC]
    0.789
    (0.232)
    0.744
    (0.307)
    0.833
    (0.0739)
    1.14
    (0.0991)
    1.37
    (0.278)
    1.04
    (0.731)
    0.712
    (0.205)
    0.829
    (0.177)
    0.723
    (0.315)
    0.987
    (0.35)
    40. Secondary Outcome
    Title Phase Ib and Phase II: Pharmacokinetics of PDR001 - Accumulation Ratio (AR)
    Description Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - PDR001
    Time Frame cycle 4 (day 84)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 3 6 4 2 3 3 5 3 4 13
    Mean (Standard Deviation) [Ratio of AUC]
    1.48
    (0.17)
    1.15
    (0.522)
    1.14
    (0.176)
    1.89
    (0.84)
    1.85
    (0.348)
    1.5
    (0.848)
    1.08
    (0.235)
    1.56
    (0.593)
    2.05
    (0.156)
    1.54
    (0.664)
    41. Secondary Outcome
    Title Phase Ib and Phase II: All Collected Deaths
    Description On treatment deaths are reported from the start of treatment until end of study treatment plus 30 days, up to maximum duration of 116.4 weeks for phase Ib and 92.4 weeks for phase II. Deaths post treatment survival follow up are reported after the on-treatment period, up to a maximum timeframe of 46 months (3.8 years).
    Time Frame For ontreatment deaths: up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II. For total deaths: up to 3.8 years

    Outcome Measure Data

    Analysis Population Description
    Clinical Database Population
    Arm/Group Title Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME
    Arm/Group Description Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)
    Measure Participants 6 12 12 13 6 11 20 20 21 20
    Total Deaths
    6
    100%
    12
    100%
    10
    83.3%
    12
    92.3%
    4
    66.7%
    10
    90.9%
    11
    55%
    19
    95%
    14
    66.7%
    11
    55%
    On-treatment Deaths
    0
    0%
    1
    8.3%
    4
    33.3%
    4
    30.8%
    1
    16.7%
    4
    36.4%
    1
    5%
    3
    15%
    0
    0%
    2
    10%

    Adverse Events

    Time Frame On-treatment adverse events are reported, from first dose of study treatment until end of study treatment plus 30 days, up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II.
    Adverse Event Reporting Description
    Arm/Group Title Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    Arm/Group Description Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    All Cause Mortality
    Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 1/12 (8.3%) 4/12 (33.3%) 4/13 (30.8%) 1/6 (16.7%) 4/11 (36.4%) 1/20 (5%) 3/20 (15%) 0/21 (0%) 2/20 (10%)
    Serious Adverse Events
    Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/6 (50%) 4/12 (33.3%) 4/12 (33.3%) 7/13 (53.8%) 2/6 (33.3%) 5/11 (45.5%) 8/20 (40%) 14/20 (70%) 8/21 (38.1%) 7/20 (35%)
    Blood and lymphatic system disorders
    Anaemia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/6 (16.7%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 2/20 (10%) 0/21 (0%) 0/20 (0%)
    Ascites 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Constipation 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Dyspepsia 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Gastric haemorrhage 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 1/20 (5%)
    Gastrointestinal haemorrhage 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Haemoperitoneum 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Intestinal obstruction 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Intestinal perforation 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Large intestinal obstruction 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Lower gastrointestinal haemorrhage 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Nausea 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Rectal haemorrhage 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Vomiting 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    General disorders
    Asthenia 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Chills 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Fatigue 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    General physical health deterioration 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Generalised oedema 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pyrexia 0/6 (0%) 0/12 (0%) 0/12 (0%) 2/13 (15.4%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 2/20 (10%) 0/21 (0%) 0/20 (0%)
    Ulcer 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hepatobiliary disorders
    Bile duct obstruction 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Cholecystitis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Jaundice cholestatic 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Infections and infestations
    Cystitis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Febrile infection 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Infection 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Peritonitis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pneumocystis jirovecii pneumonia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pneumonia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Sepsis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Skin infection 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Upper respiratory tract infection 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Urinary tract infection 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 1/20 (5%)
    Injury, poisoning and procedural complications
    Gastrointestinal procedural complication 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Infusion related reaction 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 1/20 (5%)
    Investigations
    Alanine aminotransferase increased 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Aspartate aminotransferase increased 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Blood creatinine increased 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hyperkalaemia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Hypoglycaemia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Hyponatraemia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hypophosphataemia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Bone pain 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Fistula 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Flank pain 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Pain in extremity 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Infected neoplasm 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Lymphangiosis carcinomatosa 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Metastases to central nervous system 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Tumour pain 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Nervous system disorders
    Cerebral infarction 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Guillain-Barre syndrome 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Seizure 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Product Issues
    Device breakage 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Renal and urinary disorders
    Anuria 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Renal failure 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Renal impairment 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 2/20 (10%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Pleural effusion 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pneumonia aspiration 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pneumonitis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Pneumothorax 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Respiratory failure 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Skin and subcutaneous tissue disorders
    Rash papular 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Vascular disorders
    Deep vein thrombosis 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Hypertensive crisis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Thrombosis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Other (Not Including Serious) Adverse Events
    Ph Ib: MCS110@1 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 100@mg Q3W Ph Ib: MCS110@3 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W Ph Ib: MCS110@10 mg/kg Q3W@+ PDR001 300@mg Q3W Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - TNBC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - PC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - EC Ph II: MCS110@7.5 mg/kg Q3W@+ PDR001 300@mg Q3W - ME
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 12/12 (100%) 12/12 (100%) 13/13 (100%) 6/6 (100%) 11/11 (100%) 20/20 (100%) 20/20 (100%) 21/21 (100%) 20/20 (100%)
    Blood and lymphatic system disorders
    Anaemia 4/6 (66.7%) 2/12 (16.7%) 3/12 (25%) 3/13 (23.1%) 3/6 (50%) 3/11 (27.3%) 4/20 (20%) 6/20 (30%) 5/21 (23.8%) 7/20 (35%)
    Leukocytosis 0/6 (0%) 0/12 (0%) 0/12 (0%) 2/13 (15.4%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Cardiac disorders
    Tachycardia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Ear and labyrinth disorders
    Vertigo 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Endocrine disorders
    Hypopituitarism 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hypothyroidism 1/6 (16.7%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 2/11 (18.2%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Eye disorders
    Dry eye 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 1/20 (5%)
    Eye pruritus 1/6 (16.7%) 2/12 (16.7%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Eyelid oedema 0/6 (0%) 3/12 (25%) 1/12 (8.3%) 1/13 (7.7%) 0/6 (0%) 2/11 (18.2%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Lacrimation increased 1/6 (16.7%) 4/12 (33.3%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Panophthalmitis 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Periorbital oedema 0/6 (0%) 3/12 (25%) 2/12 (16.7%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 3/20 (15%) 3/20 (15%) 4/21 (19%) 6/20 (30%)
    Uveitis 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Visual impairment 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Xerophthalmia 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Abdominal distension 1/6 (16.7%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Abdominal pain 2/6 (33.3%) 3/12 (25%) 3/12 (25%) 3/13 (23.1%) 1/6 (16.7%) 1/11 (9.1%) 0/20 (0%) 3/20 (15%) 3/21 (14.3%) 1/20 (5%)
    Abdominal pain lower 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Abdominal pain upper 0/6 (0%) 1/12 (8.3%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 3/20 (15%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Aphthous ulcer 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Ascites 1/6 (16.7%) 1/12 (8.3%) 0/12 (0%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Colitis 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Constipation 3/6 (50%) 2/12 (16.7%) 2/12 (16.7%) 2/13 (15.4%) 2/6 (33.3%) 1/11 (9.1%) 6/20 (30%) 4/20 (20%) 4/21 (19%) 5/20 (25%)
    Diarrhoea 3/6 (50%) 1/12 (8.3%) 0/12 (0%) 1/13 (7.7%) 2/6 (33.3%) 3/11 (27.3%) 2/20 (10%) 4/20 (20%) 2/21 (9.5%) 1/20 (5%)
    Dry mouth 2/6 (33.3%) 2/12 (16.7%) 2/12 (16.7%) 1/13 (7.7%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Dyspepsia 0/6 (0%) 1/12 (8.3%) 1/12 (8.3%) 2/13 (15.4%) 1/6 (16.7%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 1/21 (4.8%) 1/20 (5%)
    Epigastric discomfort 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Flatulence 1/6 (16.7%) 1/12 (8.3%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Gastritis 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Gastrooesophageal reflux disease 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Gingival bleeding 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Haematochezia 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Melaena 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Nausea 2/6 (33.3%) 5/12 (41.7%) 3/12 (25%) 5/13 (38.5%) 1/6 (16.7%) 6/11 (54.5%) 6/20 (30%) 8/20 (40%) 6/21 (28.6%) 4/20 (20%)
    Odynophagia 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Stomatitis 1/6 (16.7%) 1/12 (8.3%) 1/12 (8.3%) 3/13 (23.1%) 1/6 (16.7%) 1/11 (9.1%) 0/20 (0%) 1/20 (5%) 1/21 (4.8%) 3/20 (15%)
    Vomiting 1/6 (16.7%) 5/12 (41.7%) 3/12 (25%) 5/13 (38.5%) 1/6 (16.7%) 1/11 (9.1%) 3/20 (15%) 4/20 (20%) 2/21 (9.5%) 0/20 (0%)
    General disorders
    Adverse reaction 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Asthenia 3/6 (50%) 5/12 (41.7%) 3/12 (25%) 3/13 (23.1%) 3/6 (50%) 5/11 (45.5%) 2/20 (10%) 3/20 (15%) 2/21 (9.5%) 3/20 (15%)
    Chest discomfort 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Chills 1/6 (16.7%) 1/12 (8.3%) 2/12 (16.7%) 2/13 (15.4%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 4/20 (20%) 3/21 (14.3%) 7/20 (35%)
    Face oedema 0/6 (0%) 2/12 (16.7%) 2/12 (16.7%) 3/13 (23.1%) 1/6 (16.7%) 1/11 (9.1%) 0/20 (0%) 1/20 (5%) 3/21 (14.3%) 6/20 (30%)
    Fatigue 2/6 (33.3%) 3/12 (25%) 5/12 (41.7%) 2/13 (15.4%) 2/6 (33.3%) 0/11 (0%) 5/20 (25%) 2/20 (10%) 4/21 (19%) 4/20 (20%)
    Gait disturbance 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    General physical health deterioration 0/6 (0%) 1/12 (8.3%) 1/12 (8.3%) 1/13 (7.7%) 2/6 (33.3%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Generalised oedema 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Influenza like illness 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Non-cardiac chest pain 1/6 (16.7%) 3/12 (25%) 2/12 (16.7%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 2/20 (10%) 1/20 (5%) 0/21 (0%) 1/20 (5%)
    Oedema peripheral 2/6 (33.3%) 1/12 (8.3%) 2/12 (16.7%) 2/13 (15.4%) 1/6 (16.7%) 1/11 (9.1%) 2/20 (10%) 3/20 (15%) 3/21 (14.3%) 3/20 (15%)
    Pyrexia 1/6 (16.7%) 4/12 (33.3%) 3/12 (25%) 1/13 (7.7%) 0/6 (0%) 5/11 (45.5%) 4/20 (20%) 4/20 (20%) 1/21 (4.8%) 8/20 (40%)
    Suprapubic pain 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hepatobiliary disorders
    Cholestasis 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hyperbilirubinaemia 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Portal vein thrombosis 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Immune system disorders
    Cytokine release syndrome 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Infections and infestations
    Abscess 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Cellulitis 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Conjunctivitis 1/6 (16.7%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Diarrhoea infectious 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Helicobacter infection 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Infection 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Influenza 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Nasopharyngitis 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Otitis media 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Peritonitis 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pneumonia 0/6 (0%) 2/12 (16.7%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 1/20 (5%) 1/20 (5%) 0/21 (0%) 3/20 (15%)
    Pyuria 0/6 (0%) 0/12 (0%) 0/12 (0%) 2/13 (15.4%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Respiratory tract infection 2/6 (33.3%) 2/12 (16.7%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Skin infection 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 2/20 (10%)
    Upper respiratory tract infection 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 2/11 (18.2%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Urinary tract infection 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 2/6 (33.3%) 1/11 (9.1%) 2/20 (10%) 1/20 (5%) 2/21 (9.5%) 0/20 (0%)
    Viral skin infection 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Injury, poisoning and procedural complications
    Abdominal injury 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Fall 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Foot fracture 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Infusion related reaction 1/6 (16.7%) 3/12 (25%) 1/12 (8.3%) 0/13 (0%) 1/6 (16.7%) 1/11 (9.1%) 3/20 (15%) 2/20 (10%) 3/21 (14.3%) 1/20 (5%)
    Post procedural haemorrhage 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Post procedural inflammation 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Procedural pain 1/6 (16.7%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Rib fracture 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Alanine aminotransferase increased 1/6 (16.7%) 1/12 (8.3%) 2/12 (16.7%) 1/13 (7.7%) 1/6 (16.7%) 2/11 (18.2%) 4/20 (20%) 5/20 (25%) 7/21 (33.3%) 4/20 (20%)
    Amylase increased 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 2/20 (10%)
    Aspartate aminotransferase increased 4/6 (66.7%) 3/12 (25%) 3/12 (25%) 5/13 (38.5%) 3/6 (50%) 4/11 (36.4%) 9/20 (45%) 7/20 (35%) 13/21 (61.9%) 10/20 (50%)
    Blood alkaline phosphatase increased 0/6 (0%) 0/12 (0%) 3/12 (25%) 2/13 (15.4%) 0/6 (0%) 0/11 (0%) 2/20 (10%) 3/20 (15%) 3/21 (14.3%) 3/20 (15%)
    Blood bilirubin increased 3/6 (50%) 0/12 (0%) 2/12 (16.7%) 2/13 (15.4%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Blood creatine phosphokinase increased 1/6 (16.7%) 3/12 (25%) 3/12 (25%) 3/13 (23.1%) 4/6 (66.7%) 3/11 (27.3%) 9/20 (45%) 10/20 (50%) 12/21 (57.1%) 14/20 (70%)
    Blood creatinine increased 1/6 (16.7%) 2/12 (16.7%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 2/21 (9.5%) 1/20 (5%)
    Blood lactate dehydrogenase increased 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 1/11 (9.1%) 3/20 (15%) 1/20 (5%) 2/21 (9.5%) 5/20 (25%)
    Blood pressure increased 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Blood thyroid stimulating hormone increased 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    C-reactive protein increased 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Lipase increased 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 2/20 (10%)
    Lymphocyte count decreased 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 2/20 (10%) 2/20 (10%) 0/21 (0%) 1/20 (5%)
    Neutrophil count increased 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Platelet count decreased 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 2/20 (10%)
    Transaminases increased 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Weight decreased 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 2/20 (10%) 0/21 (0%) 1/20 (5%)
    Metabolism and nutrition disorders
    Decreased appetite 3/6 (50%) 7/12 (58.3%) 4/12 (33.3%) 1/13 (7.7%) 0/6 (0%) 4/11 (36.4%) 3/20 (15%) 7/20 (35%) 1/21 (4.8%) 4/20 (20%)
    Dehydration 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Hyperglycaemia 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 1/20 (5%) 1/21 (4.8%) 0/20 (0%)
    Hyperkalaemia 0/6 (0%) 0/12 (0%) 2/12 (16.7%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 1/21 (4.8%) 0/20 (0%)
    Hypermagnesaemia 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hyperuricaemia 1/6 (16.7%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Hypoalbuminaemia 1/6 (16.7%) 0/12 (0%) 2/12 (16.7%) 1/13 (7.7%) 2/6 (33.3%) 0/11 (0%) 0/20 (0%) 2/20 (10%) 1/21 (4.8%) 1/20 (5%)
    Hypocalcaemia 0/6 (0%) 0/12 (0%) 2/12 (16.7%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 1/21 (4.8%) 0/20 (0%)
    Hypokalaemia 0/6 (0%) 0/12 (0%) 0/12 (0%) 2/13 (15.4%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 1/20 (5%)
    Hypomagnesaemia 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hyponatraemia 1/6 (16.7%) 1/12 (8.3%) 2/12 (16.7%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 3/20 (15%) 2/21 (9.5%) 1/20 (5%)
    Hypophagia 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hypophosphataemia 1/6 (16.7%) 1/12 (8.3%) 1/12 (8.3%) 4/13 (30.8%) 2/6 (33.3%) 1/11 (9.1%) 0/20 (0%) 1/20 (5%) 1/21 (4.8%) 1/20 (5%)
    Vitamin D deficiency 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/6 (16.7%) 3/12 (25%) 1/12 (8.3%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 3/20 (15%) 0/20 (0%) 1/21 (4.8%) 1/20 (5%)
    Arthritis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Back pain 1/6 (16.7%) 2/12 (16.7%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 2/20 (10%) 2/20 (10%) 1/21 (4.8%) 2/20 (10%)
    Flank pain 0/6 (0%) 4/12 (33.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Groin pain 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Joint stiffness 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Joint warmth 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Muscle spasms 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Muscle twitching 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Muscular weakness 1/6 (16.7%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Musculoskeletal chest pain 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 1/20 (5%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Myalgia 0/6 (0%) 1/12 (8.3%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 4/20 (20%) 2/21 (9.5%) 0/20 (0%)
    Neck pain 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pain in extremity 0/6 (0%) 1/12 (8.3%) 2/12 (16.7%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 2/20 (10%) 0/20 (0%) 0/21 (0%) 1/20 (5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 1/20 (5%)
    Metastases to central nervous system 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Tumour pain 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 3/21 (14.3%) 1/20 (5%)
    Nervous system disorders
    Balance disorder 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Dizziness 0/6 (0%) 1/12 (8.3%) 1/12 (8.3%) 2/13 (15.4%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 0/20 (0%) 2/21 (9.5%) 1/20 (5%)
    Dysgeusia 0/6 (0%) 2/12 (16.7%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Headache 1/6 (16.7%) 1/12 (8.3%) 1/12 (8.3%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 5/20 (25%) 0/20 (0%) 3/21 (14.3%) 1/20 (5%)
    Hypoaesthesia 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Neuropathy peripheral 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 2/20 (10%) 0/21 (0%) 0/20 (0%)
    Paraesthesia 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Somnolence 0/6 (0%) 0/12 (0%) 3/12 (25%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Psychiatric disorders
    Anxiety 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 1/20 (5%) 1/20 (5%) 3/21 (14.3%) 0/20 (0%)
    Confusional state 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Depression 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 1/21 (4.8%) 0/20 (0%)
    Disorientation 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Eating disorder 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Insomnia 1/6 (16.7%) 2/12 (16.7%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 3/20 (15%) 1/20 (5%) 2/21 (9.5%) 1/20 (5%)
    Renal and urinary disorders
    Choluria 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Dysuria 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Haematuria 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 1/20 (5%)
    Pollakiuria 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Proteinuria 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 2/21 (9.5%) 2/20 (10%)
    Renal colic 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Renal failure 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Ureterolithiasis 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Reproductive system and breast disorders
    Breast pain 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 2/20 (10%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Metrorrhagia 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Varicocele 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Respiratory, thoracic and mediastinal disorders
    Aphonia 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Cough 0/6 (0%) 3/12 (25%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 1/20 (5%) 1/20 (5%) 0/21 (0%) 1/20 (5%)
    Dysphonia 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Dyspnoea 2/6 (33.3%) 2/12 (16.7%) 2/12 (16.7%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 2/20 (10%) 1/20 (5%) 3/21 (14.3%) 1/20 (5%)
    Epistaxis 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Haemoptysis 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 1/20 (5%)
    Lung opacity 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Nasal congestion 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Nasal mucosal ulcer 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Oropharyngeal pain 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Pleural effusion 0/6 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 1/20 (5%) 1/21 (4.8%) 0/20 (0%)
    Pneumonitis 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 1/21 (4.8%) 0/20 (0%)
    Productive cough 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pulmonary embolism 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 1/20 (5%) 1/21 (4.8%) 0/20 (0%)
    Respiratory failure 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 1/11 (9.1%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Rhinalgia 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Rhinorrhoea 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Dry skin 1/6 (16.7%) 0/12 (0%) 2/12 (16.7%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 1/20 (5%) 1/20 (5%) 0/21 (0%) 0/20 (0%)
    Hair colour changes 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hyperhidrosis 1/6 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Intertrigo 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Nail dystrophy 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Petechiae 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Pruritus 1/6 (16.7%) 1/12 (8.3%) 2/12 (16.7%) 0/13 (0%) 1/6 (16.7%) 0/11 (0%) 2/20 (10%) 2/20 (10%) 2/21 (9.5%) 1/20 (5%)
    Rash 0/6 (0%) 2/12 (16.7%) 2/12 (16.7%) 0/13 (0%) 1/6 (16.7%) 1/11 (9.1%) 3/20 (15%) 2/20 (10%) 2/21 (9.5%) 4/20 (20%)
    Rash maculo-papular 0/6 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 1/20 (5%) 2/21 (9.5%) 2/20 (10%)
    Rash pruritic 0/6 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/6 (0%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Vascular disorders
    Deep vein thrombosis 0/6 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 1/6 (16.7%) 0/11 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/20 (0%)
    Hypertension 0/6 (0%) 1/12 (8.3%) 1/12 (8.3%) 1/13 (7.7%) 1/6 (16.7%) 1/11 (9.1%) 1/20 (5%) 1/20 (5%) 2/21 (9.5%) 4/20 (20%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone + 1 862 778 8300
    Email Novartis.email@Novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02807844
    Other Study ID Numbers:
    • CMCS110Z2102
    • 2016-000210-29
    First Posted:
    Jun 21, 2016
    Last Update Posted:
    Aug 11, 2021
    Last Verified:
    Jul 1, 2021