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Phase 1/2 Study of Mocetinostat and Durvalumab in Patients With Advanced Solid Tumors and NSCLC

Sponsor
Mirati Therapeutics Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02805660
Collaborator
(none)
83
Enrollment
15
Locations
7
Arms
42.6
Actual Duration (Months)
5.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Mocetinostat (MGCD0103) is an orally administered HDAC inhibitor. Durvalumab (MEDI4736) is a human monoclonal antibody that is an inhibitor of the Programmed Cell Death Ligand (or PD-L1). Durvalumab is also known as a checkpoint inhibitor.

This study is evaluating the combination regimen of mocetinostat and durvalumab in participants with Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer.

Condition or Disease Intervention/Treatment Phase
  • Drug: Mocetinostat - 50 mg
  • Drug: Mocetinostat - 70 mg
  • Drug: Mocetinostat - 90 mg
  • Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg)
  • Drug: Durvalumab - 1500 mg
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
83 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of HDAC Inhibitor, Mocetinostat, in Combination With PD-L1 Inhibitor, Durvalumab, in Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer
Actual Study Start Date :
Jun 1, 2016
Actual Primary Completion Date :
Dec 14, 2019
Actual Study Completion Date :
Dec 20, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1: Dose Escalation - 50 mg

The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.

Drug: Mocetinostat - 50 mg
Participants received mocetinostat three times weekly as an oral capsule.
Other Names:
  • MGCD0103

    • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other Names:
  • MEDI4736

    		•
    Experimental: Phase 1: Dose Escalation - 70 mg

    The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.

    Drug: Mocetinostat - 70 mg
    Participants received mocetinostat three times weekly as an oral capsule.
    Other Names:
  • MGCD0103

    • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other Names:
  • MEDI4736

    		•
    Experimental: Phase 1: Dose Escalation - 90 mg

    The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.

    Drug: Mocetinostat - 90 mg
    Participants received mocetinostat three times weekly as an oral capsule.
    Other Names:
  • MGCD0103

    • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other Names:
  • MEDI4736

    		•
    Experimental: Phase 2: Combination Regimen - Cohort 1

    Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort.

    Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other Names:
  • MGCD0103

    • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other Names:
  • MEDI4736

    		•
    Experimental: Phase 2: Combination Regimen - Cohort 2

    Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort.

    Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other Names:
  • MGCD0103

    • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other Names:
  • MEDI4736

    		•
    Experimental: Phase 2: Combination Regimen - Cohort 3

    Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort.

    Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other Names:
  • MGCD0103

    • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other Names:
  • MEDI4736

    		•
    Experimental: Phase 2: Combination Regimen - Cohort 4

    Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort.

    Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other Names:
  • MGCD0103

    • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other Names:
  • MEDI4736

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During the First 28-day Cycle of Combination Treatment In Phase 1 [28 days]

      Toxicities were graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Any of the following events considered to be causally related to treatment with mocetinostat in combination with durvalumab that occurred during Phase 1 were considered a DLT: Any Grade 4 immune-related adverse event (irAE) Grade 3 or greater colitis Grade 3 or greater noninfectious pneumonitis Grade 2 pneumonitis that did not resolve to ≤ Grade 1 within 3 days of the initiation of maximal supportive care Grade 3 irAE (excluding colitis or pneumonitis) that: Did not resolve to Grade 2 within 3 days after onset of the event despite optimal medical management including systemic corticosteroids, or Did not resolve to Grade ≤1 or Baseline within 14 days Liver transaminase elevation >8×upper limit of normal (ULN) or total bilirubin >5×ULN Grade 3 or greater non-irAE, except nausea, vomiting, anorexia, dehydration, or diarrhea

    2. Objective Response Rate (ORR) [Up to approximately 10 months]

      Objective Response Rate (ORR) was defined as the number of participants documented to have a confirmed Complete Response (CR) or Partial Response (PR). Complete Response was defined as the complete disappearance of all target lesions with the exception of nodal disease. Partial Response was defined at least a 30% decrease in the sum of diameters of target measurable lesions. Responses were determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants without response data were counted as non-responders. Inferential statistical analyses were conducted for Phase 2 only, as efficacy was not part of the Phase 1 objectives.

    Secondary Outcome Measures

    1. Number of Participants Experiencing Treatment-Emergent Adverse Events [Day 1 to 28 days after last dose of study treatment (up to a maximum of 125 weeks in phase 1 and a maximum of 92 weeks in phase 2)]

    2. Duration of Response (DR) [Up to approximately 10 months]

      DR was defined as the time in days from date of the first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the first documentation of objective Progressive Disease (PD) or to death due to any cause in the absence of documented PD. DR was only calculated for the subgroup of participants who achieved a Best Overall Response of CR or PR and was presented for responses assessed by Investigator's assessment. Data is displayed for Phase 2 only, as no participants experienced an objective response (CR or PR) during Phase 1.

    3. Clinical Benefit Rate (CBR) [Up to approximately 10 months]

      Clinical benefit rate (CBR) was defined as the number of participants documented to have a confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants who were not be able to be assessed for response were counted as non-responders.

    4. Progression-Free Survival (PFS) [Randomization until progressive disease or death due to any cause (up to 42 months)]

      Progression-free survival (PFS) was defined as the time from date of first study treatment to first Progressive Disease (PD) or death due to any cause in the absence of documented PD per RECIST v1.1

    5. 1-Year Survival Rate [1 year]

    6. Overall Survival (OS) [From date of first study treatment until death due to any cause (up to 42 months)]

      OS was defined as the time from first dose of study treatment to the date of death due to any cause.

    7. Concentration of Mocetinistat in Blood Plasma [Cycle 1 Day 1 pre-dose, 1, 3, and 7 hours post-dose, Cycle 1 Day 15 pre-dose and 1 hour post-dose, Cycle 2 Day 1 pre-dose and 1 hour post-dose, Cycle 3 Day 1 pre-dose and 1 hour post-dose and Cycle 7 Day 1 pre-dose (each cycle is 28 days)]

    8. Concentration of Durvalumab in Blood Plasma [Cycle 1 Day 1 pre-dose + end of infusion, Cycle 1 Day 15 pre-mocetinostat dose, Cycle 2 Day 1 pre-dose, Cycle 3 Day 1 pre-dose, Cycle 4 Day 1 pre-dose + end of infusion, Cycle 7 Day 1 pre-dose + 90 days after participant's last dose (Up to max 133 weeks)]

      Plasma concentration of Durvalumab was evaluated. All participants received the same Durvalumab dose regardless of Mocetinistat dose group.

    9. Number of Participants With the Presence of Anti-Drug Antibody (ADA) in the Blood [Up to approximately 10 months]

    10. Number of Participants With Tumor Expression of Programmed Cell Death Ligand 1 (PD-L1) at Baseline [Baseline]

    Eligibility Criteria

    Criteria

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

    • Phase 1-Diagnosis of advanced or metastatic solid tumor; Phase 2-Diagnosis of NSCLC

    • Not amenable to treatment with curative intent

    • Adequate bone marrow and organ function

    Exclusion Criteria:

    • Impaired heart function

    • Uncontrolled tumor in the brain

    • Other active cancer

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Southern Cancer Center, PC Mobile Alabama United States 36608
    2 David Geffen School of Medicine at UCLA Los Angeles California United States 90095
    3 Woodlands Medical Specialists - Pensacola Pensacola Florida United States 32503
    4 Robert H. Lurie Comprehensive Cancer Center of Northwestern University Chicago Illinois United States 60611
    5 NorthShore University Health System Evanston Illinois United States 60201
    6 Unniversity of Minnesota Masonic Cancer Center Minneapolis Minnesota United States 55414
    7 Hackensack University Medical Center Hackensack New Jersey United States 07601
    8 Montefiore Medical Center Bronx New York United States 10461
    9 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    10 Mary Crowley Cancer Research Centers Dallas Texas United States 75230
    11 Texas Oncology - Denton South Denton Texas United States 76210
    12 Texas Oncology-Plano West Plano Texas United States 75093
    13 Virginia Cancer Specialists Fairfax Virginia United States 22031
    14 Shenandoah Oncology - Winchester Winchester Virginia United States 22601
    15 Seattle Cancer Care Alliance Seattle Washington United States 98109

    Sponsors and Collaborators

    • Mirati Therapeutics Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Mirati Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT02805660
    Other Study ID Numbers:
    • 0103-020
    First Posted:
    Jun 20, 2016
    Last Update Posted:
    Apr 6, 2021
    Last Verified:
    Mar 1, 2021
    Keywords provided by Mirati Therapeutics Inc.
    MGCD0103
    MEDI4736
    Mocetinostat
    Durvalumab
    HDAC Inhibitor
    PD-L1 Inhibitor
    Phase 1
    Phase 2
    Metastatic Solid Tumor
    Non-small cell lung cancer
    immunotherapy
    checkpoint inhibitor
    Additional relevant MeSH terms:
    Durvalumab
    Mocetinostat

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Period Title: Overall Study
    STARTED 5 4 11 18 3 23 19
    COMPLETED 0 0 0 0 0 0 0
    NOT COMPLETED 5 4 11 18 3 23 19

    Baseline Characteristics

    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4 Total
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Total of all reporting groups
    Overall Participants 5 4 11 18 3 23 19 83
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    60%
    3
    75%
    4
    36.4%
    5
    27.8%
    0
    0%
    9
    39.1%
    9
    47.4%
    33
    39.8%
    >=65 years
    2
    40%
    1
    25%
    7
    63.6%
    13
    72.2%
    3
    100%
    14
    60.9%
    10
    52.6%
    50
    60.2%
    Sex: Female, Male (Count of Participants)
    Female
    4
    80%
    2
    50%
    6
    54.5%
    12
    66.7%
    1
    33.3%
    9
    39.1%
    8
    42.1%
    42
    50.6%
    Male
    1
    20%
    2
    50%
    5
    45.5%
    6
    33.3%
    2
    66.7%
    14
    60.9%
    11
    57.9%
    41
    49.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    25%
    1
    9.1%
    1
    5.6%
    1
    33.3%
    3
    13%
    0
    0%
    7
    8.4%
    Not Hispanic or Latino
    5
    100%
    3
    75%
    10
    90.9%
    17
    94.4%
    2
    66.7%
    20
    87%
    19
    100%
    76
    91.6%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    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%
    Asian
    0
    0%
    0
    0%
    2
    18.2%
    1
    5.6%
    0
    0%
    1
    4.3%
    2
    10.5%
    6
    7.2%
    Native Hawaiian or Other Pacific Islander
    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%
    2
    11.1%
    0
    0%
    2
    8.7%
    1
    5.3%
    5
    6%
    White
    5
    100%
    3
    75%
    8
    72.7%
    14
    77.8%
    3
    100%
    18
    78.3%
    16
    84.2%
    67
    80.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    25%
    1
    9.1%
    1
    5.6%
    0
    0%
    2
    8.7%
    0
    0%
    5
    6%
    Region of Enrollment (participants) [Number]
    United States
    5
    100%
    4
    100%
    11
    100%
    18
    100%
    3
    100%
    23
    100%
    19
    100%
    83
    100%
    Smoking History (Count of Participants)
    Non-smoker
    4
    80%
    3
    75%
    6
    54.5%
    3
    16.7%
    0
    0%
    3
    13%
    2
    10.5%
    21
    25.3%
    Current Smoker
    1
    20%
    1
    25%
    0
    0%
    3
    16.7%
    0
    0%
    3
    13%
    2
    10.5%
    10
    12%
    Former Smoker
    0
    0%
    0
    0%
    5
    45.5%
    12
    66.7%
    3
    100%
    17
    73.9%
    15
    78.9%
    52
    62.7%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During the First 28-day Cycle of Combination Treatment In Phase 1
    Description Toxicities were graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Any of the following events considered to be causally related to treatment with mocetinostat in combination with durvalumab that occurred during Phase 1 were considered a DLT: Any Grade 4 immune-related adverse event (irAE) Grade 3 or greater colitis Grade 3 or greater noninfectious pneumonitis Grade 2 pneumonitis that did not resolve to ≤ Grade 1 within 3 days of the initiation of maximal supportive care Grade 3 irAE (excluding colitis or pneumonitis) that: Did not resolve to Grade 2 within 3 days after onset of the event despite optimal medical management including systemic corticosteroids, or Did not resolve to Grade ≤1 or Baseline within 14 days Liver transaminase elevation >8×upper limit of normal (ULN) or total bilirubin >5×ULN Grade 3 or greater non-irAE, except nausea, vomiting, anorexia, dehydration, or diarrhea
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    DLT Evaluable Population - Participant must have either been on study for one full cycle and have received treatment with durvalumab and at least 9 of 12 scheduled mocetinostat doses (75%) in Cycle 1 or have experienced a DLT in Cycle 1.
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks.
    Measure Participants 4 3 6
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Objective Response Rate (ORR)
    Description Objective Response Rate (ORR) was defined as the number of participants documented to have a confirmed Complete Response (CR) or Partial Response (PR). Complete Response was defined as the complete disappearance of all target lesions with the exception of nodal disease. Partial Response was defined at least a 30% decrease in the sum of diameters of target measurable lesions. Responses were determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants without response data were counted as non-responders. Inferential statistical analyses were conducted for Phase 2 only, as efficacy was not part of the Phase 1 objectives.
    Time Frame Up to approximately 10 months

    Outcome Measure Data

    Analysis Population Description
    Clinical Activity Evaluable Population - The Clinical Activity Evaluable Population was defined as all participants who had at least one on-study disease assessment or discontinued from treatment for progressive disease (PD).
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 5 4 9 15 3 21 13
    Number (95% Confidence Interval) [Percentage of participants]
    0
    0%
    0
    0%
    0
    0%
    6.7
    37.2%
    0
    0%
    9.5
    41.3%
    23.1
    121.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Phase 2: Combination Regimen - Cohort 1
    Comments
    Type of Statistical Test Superiority
    Comments An exact test for single proportion was performed to test null hypothesis (H0): ORR <= 5% against alternative hypothesis (H1): ORR > 5% for Cohorts 1, 3, and 4 and to test H0: ORR <= 27% against H1: ORR > 27% for Cohort 2.
    Statistical Test of Hypothesis p-Value 0.537
    Comments
    Method Exact Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Phase 2: Combination Regimen - Cohort 2
    Comments
    Type of Statistical Test Superiority
    Comments An exact test for single proportion was performed to test null hypothesis (H0): ORR <= 5% against alternative hypothesis (H1): ORR > 5% for Cohorts 1, 3, and 4 and to test H0: ORR <= 27% against H1: ORR > 27% for Cohort 2.
    Statistical Test of Hypothesis p-Value >0.999
    Comments
    Method Exact Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Phase 2: Combination Regimen - Cohort 3
    Comments
    Type of Statistical Test Superiority
    Comments An exact test for single proportion was performed to test null hypothesis (H0): ORR <= 5% against alternative hypothesis (H1): ORR > 5% for Cohorts 1, 3, and 4 and to test H0: ORR <= 27% against H1: ORR > 27% for Cohort 2.
    Statistical Test of Hypothesis p-Value 0.283
    Comments
    Method Exact Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Phase 2: Combination Regimen - Cohort 4
    Comments
    Type of Statistical Test Superiority
    Comments An exact test for single proportion was performed to test null hypothesis (H0): ORR <= 5% against alternative hypothesis (H1): ORR > 5% for Cohorts 1, 3, and 4 and to test H0: ORR <= 27% against H1: ORR > 27% for Cohort 2.
    Statistical Test of Hypothesis p-Value 0.025
    Comments
    Method Exact Test
    Comments
    3. Secondary Outcome
    Title Number of Participants Experiencing Treatment-Emergent Adverse Events
    Description
    Time Frame Day 1 to 28 days after last dose of study treatment (up to a maximum of 125 weeks in phase 1 and a maximum of 92 weeks in phase 2)

    Outcome Measure Data

    Analysis Population Description
    Safety Population - The Safety population was defined as all participants who received at least 1 dose of either mocetinostat or durvalumab.
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 5 4 11 18 3 23 19
    Count of Participants [Participants]
    5
    100%
    4
    100%
    10
    90.9%
    18
    100%
    3
    100%
    23
    100%
    18
    94.7%
    4. Secondary Outcome
    Title Duration of Response (DR)
    Description DR was defined as the time in days from date of the first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the first documentation of objective Progressive Disease (PD) or to death due to any cause in the absence of documented PD. DR was only calculated for the subgroup of participants who achieved a Best Overall Response of CR or PR and was presented for responses assessed by Investigator's assessment. Data is displayed for Phase 2 only, as no participants experienced an objective response (CR or PR) during Phase 1.
    Time Frame Up to approximately 10 months

    Outcome Measure Data

    Analysis Population Description
    Clinical Activity Evaluable Population (Subgroup of Responders) - Duration of response was only calculated for the subgroup of participants achieving a CR or PR.
    Arm/Group Title Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 1 0 2 3
    Median (95% Confidence Interval) [Days]
    115
    329
    NA
    5. Secondary Outcome
    Title Clinical Benefit Rate (CBR)
    Description Clinical benefit rate (CBR) was defined as the number of participants documented to have a confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants who were not be able to be assessed for response were counted as non-responders.
    Time Frame Up to approximately 10 months

    Outcome Measure Data

    Analysis Population Description
    Clinical Activity Evaluable Population - The Clinical Activity Evaluable Population was defined as all participants who had at least one on-study disease assessment or discontinued from treatment for progressive disease (PD).
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 5 4 9 15 3 21 13
    Count of Participants [Participants]
    1
    20%
    2
    50%
    2
    18.2%
    4
    22.2%
    0
    0%
    3
    13%
    5
    26.3%
    6. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description Progression-free survival (PFS) was defined as the time from date of first study treatment to first Progressive Disease (PD) or death due to any cause in the absence of documented PD per RECIST v1.1
    Time Frame Randomization until progressive disease or death due to any cause (up to 42 months)

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 5 4 9 18 3 23 14
    Median (95% Confidence Interval) [Months]
    3
    NA
    2
    3
    4
    2
    3
    7. Secondary Outcome
    Title 1-Year Survival Rate
    Description
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 5 4 9 18 3 23 14
    Number (95% Confidence Interval) [Proportion of participants]
    0.40
    8%
    0.38
    9.5%
    0.53
    4.8%
    0.72
    4%
    1.00
    33.3%
    0.52
    2.3%
    0.50
    2.6%
    8. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from first dose of study treatment to the date of death due to any cause.
    Time Frame From date of first study treatment until death due to any cause (up to 42 months)

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 5 4 9 18 3 23 14
    Median (95% Confidence Interval) [Months]
    7
    11
    16
    NA
    NA
    15
    14
    9. Secondary Outcome
    Title Concentration of Mocetinistat in Blood Plasma
    Description
    Time Frame Cycle 1 Day 1 pre-dose, 1, 3, and 7 hours post-dose, Cycle 1 Day 15 pre-dose and 1 hour post-dose, Cycle 2 Day 1 pre-dose and 1 hour post-dose, Cycle 3 Day 1 pre-dose and 1 hour post-dose and Cycle 7 Day 1 pre-dose (each cycle is 28 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Evaluable Population - The Pharmacokinetic (PK) Evaluable Population was defined as all patients who had PK concentration data collected for mocetinostat or durvalumab. Participants were combined for analysis of mocetinistat concentrations, as prespecified in the analysis shells, based on the actual dose of mocetinistat received in each phase of the study. Pharmacokinetic measures at 3 and 7 hours post dose on Cycle 1 Day 1 were only planned for Phase 1.
    Arm/Group Title Phase 1: Mocetinostat 50 mg Phase 1: Mocetinostat 70 mg Phase 1: Mocetinostat 90 mg Phase 1: Mocetinostat 40 mg Phase 2: Mocetinostat 70 mg Phase 2: Mocetinostat 50 mg
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. One participant in Phase 1 was de-escalated to 40 mg of mocetinostat. Participants in Phase 2 who received the recommended Phase 2 dose of 70 mg of mocetinostat. Six participants in Phase 2 were de-escalated to 50 mg of mocetinostat.
    Measure Participants 9 7 11 1 63 6
    Cycle 1: Day 1 - pre-dose
    NA
    (NA)
    0.91
    (83.20)
    1.02
    (114.68)
    39.65
    (175.97)
    Cycle 1: Day 1 - 1 hour post-dose
    19.85
    (441.16)
    106.61
    (43.77)
    92.56
    (143.96)
    12.19
    (289.89)
    Cycle 1: Day 1 - 3 hours post-dose
    33.53
    (111.21)
    61.63
    (24.78)
    55.27
    (53.19)
    Cycle 1: Day 1 - 7 hours post-dose
    15.75
    (58.30)
    20.92
    (27.20)
    33.89
    (45.21)
    Cycle 1: Day 15 - pre-dose
    5.36
    (NA)
    0.98
    (95.06)
    3.84
    (202.26)
    1.92
    (127.96)
    Cycle 1: Day 15 - 1 hour post-dose
    102.67
    (7.17)
    22.30
    (14646.88)
    18.32
    (1297.79)
    10.86
    (330.59)
    Cycle 2: Day 1 - pre-dose
    0.72
    (NA)
    0.85
    (NA)
    1.22
    (83.65)
    NA
    (NA)
    1.16
    (91.63)
    0.68
    (NA)
    Cycle 2: Day 1 - 1 hour post-dose
    75.11
    (25.53)
    49.30
    (86.19)
    2.45
    (83.60)
    0.72
    (NA)
    14.65
    (396.22)
    105.00
    (NA)
    Cycle 3: Day 1 - pre-dose
    0.89
    (44.73)
    NA
    (NA)
    NA
    (NA)
    4.08
    (238.84)
    0.92
    (40.65)
    Cycle 3: Day 1 - 1 hour post-dose
    22.73
    (301.01)
    92.40
    (NA)
    0.73
    (NA)
    14.39
    (319.34)
    25.12
    (378.13)
    Cycle 7: Day 1 - pre-dose
    NA
    (NA)
    0.85
    (NA)
    1.35
    (NA)
    0.65
    (35.19)
    NA
    (NA)
    10. Secondary Outcome
    Title Concentration of Durvalumab in Blood Plasma
    Description Plasma concentration of Durvalumab was evaluated. All participants received the same Durvalumab dose regardless of Mocetinistat dose group.
    Time Frame Cycle 1 Day 1 pre-dose + end of infusion, Cycle 1 Day 15 pre-mocetinostat dose, Cycle 2 Day 1 pre-dose, Cycle 3 Day 1 pre-dose, Cycle 4 Day 1 pre-dose + end of infusion, Cycle 7 Day 1 pre-dose + 90 days after participant's last dose (Up to max 133 weeks)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Evaluable Population - The Pharmacokinetic (PK) Evaluable Population was defined as all patients who had PK concentration data collected for mocetinostat or durvalumab. Participants were combined for analysis of mocetinistat concentrations, as prespecified in the analysis shells, based on the actual dose of mocetinistat received in each phase of the study. Pharmacokinetic measures at 3 and 7 hours post dose on Cycle 1 Day 1 were only planned for Phase 1.
    Arm/Group Title Durvalumab
    Arm/Group Description Participants who received durvalumab during the study.
    Measure Participants 76
    Cycle 1: Day 1 - pre-dose
    259.18
    (334.86)
    Cycle 1: Day 1 - end of infusion
    385779.56
    (36.49)
    Cycle 1: Day 15 - pre-Mocetinostat
    102925.55
    (40.05)
    Cycle 2: Day 1 - pre-dose
    44140.86
    (130.83)
    Cycle 3: Day 1 - pre-dose
    72049.14
    (91.22)
    Cycle 4: Day 1 - pre-dose
    101852.34
    (89.01)
    Cycle 4: Day 1 - end of infusion
    365307.01
    (81.59)
    Cycle 7: Day 1 - pre-dose
    130335.14
    (70.34)
    90 days after last dose
    12304.13
    (501.74)
    11. Secondary Outcome
    Title Number of Participants With the Presence of Anti-Drug Antibody (ADA) in the Blood
    Description
    Time Frame Up to approximately 10 months

    Outcome Measure Data

    Analysis Population Description
    ADA Evaluable Population - The ADA Evaluable Population was defined as all patients who received at least 1 dose of either durvalumab or mocetinostat for whom ADA results were available.
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 1 4 9 17 3 22 15
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    9.1%
    1
    5.6%
    1
    33.3%
    1
    4.3%
    0
    0%
    12. Secondary Outcome
    Title Number of Participants With Tumor Expression of Programmed Cell Death Ligand 1 (PD-L1) at Baseline
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat Population (mITT) - The mITT Population was defined as all participants who received treatment with both mocetinostat and durvalumab on this study.
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 50 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 70 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase. Mocetinostat - 90 mg: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Measure Participants 5 4 9 18 3 23 14
    No/Low PD-L1 Expression
    0
    0%
    0
    0%
    0
    0%
    17
    94.4%
    0
    0%
    6
    26.1%
    9
    47.4%
    High PD-L1 Expression
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    3
    100%
    8
    34.8%
    1
    5.3%
    Missing
    5
    100%
    4
    100%
    8
    72.7%
    1
    5.6%
    0
    0%
    9
    39.1%
    4
    21.1%

    Adverse Events

    Time Frame Adverse events (AEs) are reported from the first day of study treatment until at least 28 days after last dose of study drug, and until resolution or stabilization of acute AEs (up to 125 weeks in Phase 1 and 92 weeks in Phase 2.) Serious adverse events (SAEs) are reported from the time of informed consent until 90 days after the last administration of mocetinostat or durvalumab (up to 133 weeks in Phase 1 and 101 weeks in Phase 2.)
    Adverse Event Reporting Description
    Arm/Group Title Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    Arm/Group Description The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this phase. Mocetinostat: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this phase. Mocetinostat: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this phase. Mocetinostat: Participants received mocetinostat three times weekly as an oral capsule. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg). Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort. Durvalumab - 1500 mg: Participants received durvalumab as an intravenous infusion every 4 weeks. Mocetinostat - Recommended Phase 2 Dose (70 mg): Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    All Cause Mortality
    Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    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 5/5 (100%) 2/4 (50%) 9/11 (81.8%) 5/18 (27.8%) 0/3 (0%) 14/23 (60.9%) 12/19 (63.2%)
    Serious Adverse Events
    Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    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 4/5 (80%) 1/4 (25%) 4/11 (36.4%) 6/18 (33.3%) 2/3 (66.7%) 5/23 (21.7%) 11/19 (57.9%)
    Cardiac disorders
    Pericardial effusion 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Atrial fibrillation 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Pericarditis 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Cardiac tamponade 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Gastrointestinal disorders
    Colitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Nausea 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Oesophagitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Vomiting 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    General disorders
    Axillary pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Mucosal inflammation 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Non-cardiac chest pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 0/19 (0%)
    Pyrexia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Infections and infestations
    Pneumonia 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 2/23 (8.7%) 4/19 (21.1%)
    Sepsis 0/5 (0%) 1/4 (25%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Septic shock 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Bacterial infection 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Clostridium difficile colitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 0/19 (0%)
    Gastroenteritis adenovirus 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Herpes zoster 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Pyelonephritis 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Urinary tract infection 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Injury, poisoning and procedural complications
    Contusion 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Femur fracture 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 0/19 (0%)
    Investigations
    Ejection fraction decreased 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Dehydration 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hypercalcaemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hyponatraemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression 1/5 (20%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Nervous system disorders
    Encephalopathy 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Syncope 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Psychiatric disorders
    Confusional state 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Delirium 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Renal and urinary disorders
    Urinary tract obstruction 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Pulmonary embolism 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Bronchostenosis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Dyspnoea 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Respiratory failure 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Vascular disorders
    Hypotension 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Other (Not Including Serious) Adverse Events
    Phase 1: Dose Escalation - 50 mg Phase 1: Dose Escalation - 70 mg Phase 1: Dose Escalation - 90 mg Phase 2: Combination Regimen - Cohort 1 Phase 2: Combination Regimen - Cohort 2 Phase 2: Combination Regimen - Cohort 3 Phase 2: Combination Regimen - Cohort 4
    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 5/5 (100%) 4/4 (100%) 10/11 (90.9%) 18/18 (100%) 3/3 (100%) 23/23 (100%) 18/19 (94.7%)
    Blood and lymphatic system disorders
    Anaemia 0/5 (0%) 1/4 (25%) 3/11 (27.3%) 3/18 (16.7%) 1/3 (33.3%) 1/23 (4.3%) 3/19 (15.8%)
    Neutropenia 2/5 (40%) 0/4 (0%) 3/11 (27.3%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Lymphadenopathy 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Iron deficiency anaemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Leukocytosis 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Leukopenia 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Lymphopenia 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Pancytopenia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Thrombocytopenia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Cardiac disorders
    Atrial fibrillation 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 2/23 (8.7%) 3/19 (15.8%)
    Pericardial effusion 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 1/3 (33.3%) 2/23 (8.7%) 0/19 (0%)
    Palpitations 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Pericarditis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Sinus tachycardia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 1/19 (5.3%)
    Angina pectoris 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Sinus node dysfunction 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Ventricular tachycardia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Ear and labyrinth disorders
    Ear pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hyperacusis 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hypoacusis 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Vertigo 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Vestibular disorder 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Endocrine disorders
    Hypothyroidism 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Hyperthyroidism 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Inappropriate antidiuretic hormone secretion 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Eye disorders
    Vision blurred 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Conjunctival haemorrhage 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Dry eye 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Episcleritis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Eye swelling 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Visual impairment 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Gastrointestinal disorders
    Nausea 4/5 (80%) 2/4 (50%) 9/11 (81.8%) 7/18 (38.9%) 3/3 (100%) 10/23 (43.5%) 5/19 (26.3%)
    Diarrhoea 2/5 (40%) 3/4 (75%) 4/11 (36.4%) 9/18 (50%) 1/3 (33.3%) 11/23 (47.8%) 9/19 (47.4%)
    Vomiting 4/5 (80%) 1/4 (25%) 8/11 (72.7%) 4/18 (22.2%) 1/3 (33.3%) 6/23 (26.1%) 5/19 (26.3%)
    Constipation 2/5 (40%) 1/4 (25%) 1/11 (9.1%) 3/18 (16.7%) 1/3 (33.3%) 6/23 (26.1%) 2/19 (10.5%)
    Gastrooesophageal reflux disease 2/5 (40%) 0/4 (0%) 2/11 (18.2%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Abdominal pain 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 1/18 (5.6%) 0/3 (0%) 3/23 (13%) 0/19 (0%)
    Abdominal pain upper 2/5 (40%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Ascites 1/5 (20%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Colitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 1/3 (33.3%) 0/23 (0%) 1/19 (5.3%)
    Dry mouth 1/5 (20%) 1/4 (25%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Dyspepsia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 1/23 (4.3%) 1/19 (5.3%)
    Flatulence 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Abdominal distension 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Abdominal pain lower 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Dysphagia 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Oral pain 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Stomatitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Toothache 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Anal incontinence 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Anorectal discomfort 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Anorectal disorder 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Cheilitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Gastritis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Gastrointestinal haemorrhage 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Gastrointestinal wall thickening 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Haematemesis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hiatus hernia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Lip swelling 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Oesophageal dilatation 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Proctalgia 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    General disorders
    Fatigue 4/5 (80%) 2/4 (50%) 7/11 (63.6%) 11/18 (61.1%) 3/3 (100%) 14/23 (60.9%) 8/19 (42.1%)
    Oedema peripheral 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 1/18 (5.6%) 0/3 (0%) 3/23 (13%) 3/19 (15.8%)
    Non-cardiac chest pain 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 1/18 (5.6%) 2/3 (66.7%) 2/23 (8.7%) 2/19 (10.5%)
    Asthenia 1/5 (20%) 0/4 (0%) 1/11 (9.1%) 2/18 (11.1%) 0/3 (0%) 2/23 (8.7%) 1/19 (5.3%)
    Pyrexia 0/5 (0%) 1/4 (25%) 2/11 (18.2%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Chills 0/5 (0%) 1/4 (25%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Chest discomfort 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Chest pain 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 3/19 (15.8%)
    Pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 3/19 (15.8%)
    Early satiety 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Axillary pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Catheter site discharge 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Facial pain 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Local swelling 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Malaise 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Nodule 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Peripheral swelling 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Immune system disorders
    Drug hypersensitivity 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Infections and infestations
    Urinary tract infection 1/5 (20%) 0/4 (0%) 0/11 (0%) 4/18 (22.2%) 0/3 (0%) 3/23 (13%) 2/19 (10.5%)
    Cystitis 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 1/18 (5.6%) 1/3 (33.3%) 1/23 (4.3%) 0/19 (0%)
    Bronchitis 1/5 (20%) 0/4 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Sinusitis 2/5 (40%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Upper respiratory tract infection 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 1/23 (4.3%) 1/19 (5.3%)
    Influenza 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Nasopharyngitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Oral candidiasis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Pneumonia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Sepsis 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Bacteraemia 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Clostridium difficile infection 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Folliculitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Furuncle 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Herpes zoster 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Infected cyst 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Lung infection 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Nasal herpes 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Injury, poisoning and procedural complications
    Fall 0/5 (0%) 0/4 (0%) 0/11 (0%) 2/18 (11.1%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Medication error 0/5 (0%) 0/4 (0%) 0/11 (0%) 2/18 (11.1%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hand fracture 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Infusion related reaction 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Overdose 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Radiation oesophagitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Skin abrasion 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Stoma site irritation 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Investigations
    Weight decreased 1/5 (20%) 1/4 (25%) 3/11 (27.3%) 3/18 (16.7%) 0/3 (0%) 3/23 (13%) 2/19 (10.5%)
    Alanine aminotransferase increased 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Aspartate aminotransferase increased 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Blood creatinine increased 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Electrocardiogram QT prolonged 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 1/3 (33.3%) 1/23 (4.3%) 0/19 (0%)
    Blood alkaline phosphatase increased 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Blood bilirubin increased 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Ejection fraction decreased 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 1/19 (5.3%)
    Neutrophil count decreased 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    White blood cell count decreased 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Blood alkaline phosphatase decreased 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Blood urine present 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Gamma-glutamyltransferase increased 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Haemoglobin decreased 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Lipase increased 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Platelet count decreased 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 3/5 (60%) 1/4 (25%) 4/11 (36.4%) 7/18 (38.9%) 1/3 (33.3%) 7/23 (30.4%) 5/19 (26.3%)
    Dehydration 2/5 (40%) 1/4 (25%) 0/11 (0%) 4/18 (22.2%) 1/3 (33.3%) 3/23 (13%) 5/19 (26.3%)
    Hypokalaemia 0/5 (0%) 0/4 (0%) 6/11 (54.5%) 2/18 (11.1%) 0/3 (0%) 3/23 (13%) 2/19 (10.5%)
    Hyponatraemia 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 4/23 (17.4%) 1/19 (5.3%)
    Hypoalbuminaemia 0/5 (0%) 0/4 (0%) 3/11 (27.3%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Hypocalcaemia 0/5 (0%) 0/4 (0%) 3/11 (27.3%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Hypomagnesaemia 1/5 (20%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 2/23 (8.7%) 0/19 (0%)
    Hyperglycaemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Hyperkalaemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 2/23 (8.7%) 0/19 (0%)
    Hypermagnesaemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Hypophosphataemia 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Appetite disorder 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hypercalcaemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hypernatraemia 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hypochloraemia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Malnutrition 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 4/18 (22.2%) 1/3 (33.3%) 2/23 (8.7%) 4/19 (21.1%)
    Arthralgia 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 2/18 (11.1%) 2/3 (66.7%) 1/23 (4.3%) 1/19 (5.3%)
    Flank pain 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 0/3 (0%) 3/23 (13%) 1/19 (5.3%)
    Muscular weakness 1/5 (20%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 4/23 (17.4%) 0/19 (0%)
    Musculoskeletal chest pain 1/5 (20%) 0/4 (0%) 0/11 (0%) 3/18 (16.7%) 0/3 (0%) 2/23 (8.7%) 0/19 (0%)
    Muscle spasms 2/5 (40%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Pain in extremity 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Arthritis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 0/19 (0%)
    Groin pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 0/19 (0%)
    Joint swelling 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Muscle twitching 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Musculoskeletal pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Myalgia 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Osteoarthritis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Pain in jaw 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Nervous system disorders
    Dizziness 1/5 (20%) 1/4 (25%) 2/11 (18.2%) 2/18 (11.1%) 0/3 (0%) 4/23 (17.4%) 1/19 (5.3%)
    Headache 2/5 (40%) 0/4 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/3 (0%) 2/23 (8.7%) 1/19 (5.3%)
    Dysgeusia 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 0/18 (0%) 1/3 (33.3%) 1/23 (4.3%) 0/19 (0%)
    Neuropathy peripheral 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 2/23 (8.7%) 1/19 (5.3%)
    Hypoaesthesia 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Neuralgia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 2/23 (8.7%) 0/19 (0%)
    Paraesthesia 1/5 (20%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Peripheral sensory neuropathy 1/5 (20%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Seizure 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Syncope 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Brain oedema 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Cognitive disorder 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Disturbance in attention 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Dysaesthesia 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Encephalopathy 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Lethargy 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Memory impairment 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Migraine 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Muscle contractions involuntary 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Sciatica 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Sinus headache 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Somnolence 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Tremor 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Product Issues
    Device occlusion 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Psychiatric disorders
    Insomnia 0/5 (0%) 1/4 (25%) 1/11 (9.1%) 1/18 (5.6%) 1/3 (33.3%) 2/23 (8.7%) 2/19 (10.5%)
    Confusional state 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Depression 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 1/19 (5.3%)
    Agitation 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Anxiety 0/5 (0%) 1/4 (25%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Renal and urinary disorders
    Dysuria 0/5 (0%) 0/4 (0%) 3/11 (27.3%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Haematuria 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Pollakiuria 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 2/23 (8.7%) 0/19 (0%)
    Urinary hesitation 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Urinary retention 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Reproductive system and breast disorders
    Pelvic pain 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Vaginal haemorrhage 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/5 (40%) 0/4 (0%) 1/11 (9.1%) 6/18 (33.3%) 0/3 (0%) 4/23 (17.4%) 4/19 (21.1%)
    Dyspnoea 2/5 (40%) 0/4 (0%) 3/11 (27.3%) 4/18 (22.2%) 0/3 (0%) 4/23 (17.4%) 3/19 (15.8%)
    Dyspnoea exertional 1/5 (20%) 0/4 (0%) 1/11 (9.1%) 2/18 (11.1%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Epistaxis 0/5 (0%) 1/4 (25%) 1/11 (9.1%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Haemoptysis 0/5 (0%) 0/4 (0%) 0/11 (0%) 3/18 (16.7%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Hiccups 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Pleural effusion 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Productive cough 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Pulmonary embolism 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 1/3 (33.3%) 0/23 (0%) 0/19 (0%)
    Sinus congestion 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Oropharyngeal pain 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Pneumonitis 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 2/19 (10.5%)
    Rhinorrhoea 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Chronic obstructive pulmonary disease 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Nasal discomfort 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Orthopnoea 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Paranasal sinus discomfort 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Pulmonary congestion 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Pulmonary hypertension 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Skin and subcutaneous tissue disorders
    Pruritus 1/5 (20%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 2/19 (10.5%)
    Rash 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 3/19 (15.8%)
    Dry skin 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 2/23 (8.7%) 1/19 (5.3%)
    Erythema 1/5 (20%) 1/4 (25%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Rash generalised 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 1/19 (5.3%)
    Rash papular 0/5 (0%) 0/4 (0%) 0/11 (0%) 2/18 (11.1%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Skin ulcer 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Umbilical erythema 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 1/23 (4.3%) 0/19 (0%)
    Alopecia 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Dermatitis atopic 1/5 (20%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Pain of skin 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Petechiae 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Rash maculo-papular 0/5 (0%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Rash pruritic 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Skin depigmentation 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Skin hyperpigmentation 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Skin lesion 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 1/19 (5.3%)
    Skin mass 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Vascular disorders
    Hypotension 0/5 (0%) 0/4 (0%) 2/11 (18.2%) 3/18 (16.7%) 0/3 (0%) 0/23 (0%) 3/19 (15.8%)
    Deep vein thrombosis 0/5 (0%) 1/4 (25%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 1/19 (5.3%)
    Orthostatic hypotension 1/5 (20%) 0/4 (0%) 1/11 (9.1%) 0/18 (0%) 0/3 (0%) 0/23 (0%) 0/19 (0%)
    Hot flush 0/5 (0%) 0/4 (0%) 0/11 (0%) 0/18 (0%) 1/3 (33.3%) 0/23 (0%) 0/19 (0%)
    Subclavian artery stenosis 0/5 (0%) 0/4 (0%) 0/11 (0%) 1/18 (5.6%) 0/3 (0%) 0/23 (0%) 0/19 (0%)

    Limitations/Caveats

    The study was discontinued early because the Sponsor de-prioritized development of mocetinostat. The decision to stop was not due to any patient safety issues.

    More Information

    Certain Agreements

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

    PI can not disclose, discuss, or publish study results until final manuscript has been published.

    Results Point of Contact

    Name/Title Tavette Neskorik, Senior Director, Clinical Science
    Organization Mirati Therapeutics
    Phone 858-332-3552
    Email neskorikt@mirati.com
    Responsible Party:
    Mirati Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT02805660
    Other Study ID Numbers:
    • 0103-020
    First Posted:
    Jun 20, 2016
    Last Update Posted:
    Apr 6, 2021
    Last Verified:
    Mar 1, 2021