A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma or Other Solid Tumors

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02573259
Collaborator
(none)
147
Enrollment
67
Locations
5
Arms
57.3
Actual Duration (Months)
2.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Protocol B8011001 is a Phase 1, open-label, multi-center, multiple-dose, dose escalation and expansion, safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of PF-06801591 in previously treated adult patients with locally advanced or metastatic melanoma, SCCHN, ovarian carcinoma, sarcoma, NSCLC, urothelial carcinoma or other solid tumors. This is a 2 Part study whereby the safety and tolerability of increasing dose levels of intravenous (IV) or subcutaneous (SC) PF-06801591 was assessed in Part 1. Part 2 expansion is designed to further evaluate the safety and efficacy of SC PF-06801591 in patients with NSCLC or urothelial carcinoma as well as confirm the recommended Phase 2 dose.

Detailed Description

Protocol B8011001 is a Phase 1, two part, open-label, multi center, multiple-dose, safety, efficacy, PK, and PD study of PF-06801591 administered intravenously (IV) or subcutaneous (SC) in previously treated adult patients with locally advanced or metastatic melanoma, squamous cell carcinoma head and neck (SCCHN), ovarian carcinoma, sarcoma, non-small cell lung carcinoma (NSCLC), urothelial carcinoma or other solid tumors.

The first part of the study, Part 1 dose escalation, was designed to assess the safety and tolerability of increasing dose levels of IV or SC administered PF-06801591 to establish the maximum tolerated dose (MTD) using a modified Toxicity Probability Interval (mTPI) design. Part 2 expansion is designed to further evaluate the safety and efficacy of 300 mg of PF-06801591 administered SC once every 4 weeks in patients with NSCLC or urothelial carcinoma as well as confirm the recommended Phase 2 dose (RP2D). Part 1 enrollment has completed, enrollment will only be allowed for Part 2.

Study Design

Study Type:
Interventional
Actual Enrollment :
147 participants
Allocation:
Non-Randomized
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-06801591 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC MELANOMA, SQUAMOUS CELL HEAD AND NECK CANCER, OVARIAN CANCER, SARCOMA, NON-SMALL CELL LUNG CANCER, UROTHELIAL CARCINOMA OR OTHER SOLID TUMORS.
Actual Study Start Date :
Feb 10, 2016
Actual Primary Completion Date :
Nov 19, 2020
Actual Study Completion Date :
Nov 19, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm 1 PF-06801591

0.5 mg/kg IV every 21 days (Part 1)

Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 2 PF-06801591

1.0 mg/kg IV every 21 days (Part 1)

Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 3 PF-06801591

3.0 mg/kg IV every 21 days (Part 1)

Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 4 PF-06801591

10 mg/kg IV every 21 days (Part 1)

Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 5 PF-06801591

300 mg SC every 28 days (Part 1 and 2)

Drug: PF-06801591
300 mg SC every 28 days (Part 1 and 2)

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Dose-Limiting Toxicities (DLT) - Part 1 [Cycle 1 in Part 1 (21 days for IV administration of PF-06801591; 28 days for SC administration of PF-06801591)]

    DLT was defined as any of the following drug-related adverse events (AEs) occurring during the first cycle (21 days for IV dosing, 28 days for SC dosing) in Part 1: Grade 5 AE; Grade 4 neutropenia lasting >5 days from initiation of granulocyte colony stimulating factor; Grade 4 thrombocytopenia with bleeding; Platelet transfusion requirement or a platelet count <10,000/uL; Grade 4 non-hematologic AE; Grade 3 AE lasting >7 days despite optimal supportive care; Grade 3 central nervous system AE regardless of duration; met criteria for drug induced liver injury. Severity of AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.

  2. Number of Participants With All-Causality Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2 [Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)]

    AE = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of severity were defined by CTCAE v4.03. Grades of severity were defined by CTCAE v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.

  3. Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2 [Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)]

    Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AEs and SAEs were determined by the investigator. Grades of severity were defined by CTCAE v4.03. Grades of severity were defined by CTCAE v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.

  4. Number of Participants With Laboratory Test Abnormalities - Part 1 and Part 2 [Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)]

    Following parameters were analyzed for laboratory examination: hematology (anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased); chemistries (increase of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood bilirubin, CPK, creatinine, gamma-glutamyl transferase [GGT], lipase, and serum amylase); urinalysis (proteinuria); coagulation (activated partial thromboplastin time prolonged, international normalized ratio [INR] increased). Grades of severity were defined by CTCAE v4.03. Grade 0 = No Change from normal or reference range (this grade is not included in the CTCAE v4.03 document but may used in certain circumstances). Grade 1 = mild adverse event (AE). Grade 2 = moderate AE; Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.

  5. Objective Response Rate (ORR) Based on RECIST Version 1.1 - Part 2 [Baseline up to end of treatment in Part 2 (maximum of 851 days)]

    ORR was defined as percentage of participants with confirmed objective response (OR) of complete response (CR) and partial response (PR) based on RECIST version 1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis < 10 mm). All target lesions must be assessed. PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.

  6. Objective Response Rate (ORR) Based on Immune Related RECIST (irRECIST) - Part 2 [Baseline up to end of treatment in Part 2 (maximum of 851 days)]

    ORR was defined as percentage of participants with objective response (OR) of complete response (CR) and partial response (PR) based on irRECIST. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis < 10 mm). All target lesions must be assessed. PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.

Secondary Outcome Measures

  1. Maximum Plasma Concentration (Cmax) of PF-06801591 - Part 1 [Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1]

    Cmax was the maximum concentration after dose administration observed directly from the data.

  2. AUClast of PF-06801591 in Part 1. [Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1 in Part 1]

    Area Under the Concentration Versus Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point Prior to the Next Dose (AUClast) of PF-06801591 - Part 1

  3. Clearance (CL) of PF-06801591 - Part 1 [Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1]

    CL for IV dosing. CL was calculated by dose / AUCtau for Cycles 1 and 4 IV dosing. AUCtau was defined as area under the serum concentration time profile from time zero to time tau, the dosing interval, where tau = 504 hours for every 3 weeks (Q3W) IV dosing reporting arm.

  4. Volume of Distribution at Steady State (Vss) of PF-06801591 - Part 1 [Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1]

    Steady state volume of distribution of PF-0680159 for IV dosing. Vss was calculated by CL*MRT. CL was the clearance for IV dosing. MRT was the mean residence time calculated for a single IV dose as AUMCinf/AUCinf - (DOF/2). AUMCinf was the area under the moment curve from time 0 extrapolated to infinity. DOF was the duration of infusion. AUCinf was the area under the serum concentration time profile from time 0 extrapolated to infinity.

  5. Accumulation Ratio (Rac) of PF-06801591 - Part 1 [Pre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1]

    Rac was calculated by (Cycle 4 AUCtau) / (Cycle 1 AUCtau). AUCtau was Area under the serum concentration time profile from time zero to time tau, the dosing interval, where tau = 504 hours for Q3W IV dosing and tau = 672 hours for every 4 weeks (Q4W) SC dosing.

  6. Terminal Elimination Half-Life (t1/2) of PF-06801591 - Part 1 [Pre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1]

    t1/2 was calculated by Loge(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.

  7. Number of Participants With Anti-Drug Antibody (ADA) Against PF-06801591 - Part 1 and Part 2 [Baseline up to end of treatment (maximum of 851 days)]

    Number of participants with ADA positive against PF-06801591 after IV and SC dosing - Part 1 and Part 2. A participant was ADA positive if (1) baseline titer was missing or negative and participant had ≥ 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ≥ 0.602 in titer from baseline in ≥ 1 post-treatment sample (treatment-boosted). Participants who were ADA positive at baseline but did not become boosted post-treatment were considered as ADA negative.

  8. Number of Participants With Neutralizing Antibodies (NAb) Positive Against PF-06801591 - Part 1 and Part 2 [Baseline up to end of treatment (maximum of 851 days)]

    Number of participants with NAb positive against PF-06801591 after IV and SC dosing - Part 1 and Part 2. A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥ 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ≥ 0.602 in titer from baseline in ≥ 1 post-treatment sample (treatment-boosted). Participants who were NAb positive at baseline but did not become boosted post-treatment were considered as NAb negative.

  9. Percentage of Baseline PD-1 Receptor Occupancy (RO) by PF-06801591 - Part 1 [Baseline, Days 1, 8, 15, 21 of Cycle 1, Day 1 of Cycles 2, 3, 5, Days 1, 15, 21 of Cycle 4, and end of treatment (EOT) in Part 1 (cycle = 21 days for IV dosing; cycle = 28 days for SC dosing)]

    PD-1 RO by sasanlimab was measured by the reduction of free receptor on the surface of CD8+ effector cells (CD3+, CD4-, CD8+, CD45RA+, CCR7-, CD279+) and CD8+ effector memory cells (CD3+, CD4-, CD8+, CD45RA-, CCR7-, CD279+) presented in pre- and postdose whole blood samples by flow cytometry. Percentage of baseline (ie, normalized change from baseline) PD-1 RO were calculated as [(percentage of cells at Cycle X Day X)/(percentage of cells at baseline)]*100, and are reported for this outcome measure. Baseline was defined as the most recent non-missing value prior to dosing.

  10. Number of Participants Achieving Objective Response (OR) Based on RECIST Version 1.1 - Part 1 [Baseline up to end of treatment in Part 1 (maximum of 1606 days)]

    Number of participants achieving confirmed OR based on RECIST version 1.1 in Part 1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis < 10 mm). All target lesions must be assessed. PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.

  11. Number of Participants Achieving Objective Response (OR) Based on irRECIST - Part 1 [Baseline up to end of treatment in Part 1 (maximum of 1606 days)]

    Number of participants achieving confirmed OR based on irRECIST in Part 1. OR = irCR + irPR. Overall immune related complete response (irCR) was defined as complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. Overall immune related partial response (irPR) was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases >=30%.

  12. Progression-Free Survival (PFS) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2 [Baseline up to end of treatment (maximum of 1606 days)]

    PFS was defined as the time from initiation of study intervention to first documentation of tumor progression or to death due to any cause, whichever occurred first. PFS was analyzed by the Kaplan-Meier approach for each tumor type. As this outcome measure was a secondary endpoint defined in the protocol to investigate preliminary signal of efficacy, the results were analyzed and are reported for Part 1 dose-escalation groups combined to provide more statistically meaningful results, instead of results analyzed by dose level with very limited number of participants in each group.

  13. Duration of Stable Disease (DOSD) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2 [Baseline up to end of treatment (maximum of 1606 days)]

    DOSD was analyzed by the Kaplan-Meier approach for each tumor type. Stable disease (SD) was defined as not qualifying for complete response (CR), partial response (PR), or progression. All target lesions must have been assessed. Stable could follow PR only in the rare case that the sum increased by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer held. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). All target lesions must have been assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed.

  14. Duration of Response (DOR) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2 [Baseline up to end of treatment (maximum of 1606 days)]

    DOR was defined as the time from start date (which was the date of first documentation of PR or CR) to date of first documentation of objective progression or death. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. As this outcome measure was a secondary endpoint defined in the protocol to investigate preliminary signal of efficacy, the results were analyzed and are reported for Part 1 dose-escalation groups combined to provide more statistically meaningful results, instead of results analyzed by dose level with very limited number of participants in each group.

  15. Time to Response (TTR) Based on RECIST Version 1.1 - Part 2 [Baseline up to end of treatment in Part 2 (maximum of 851 days)]

    TTR was the time to confirmed or unconfirmed complete response (CR) or partial response (PR) based on investigator assessment per RECIST v1.1 by tumor type. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). All target lesions must have been assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed.

  16. Time to Progression (TTP) Based on RECIST Version 1.1 and irRECIST - Part 2 [Baseline up to end of treatment in Part 2 (maximum of 851 days)]

    TTP was the time to objective progression. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. TTP was analyzed by the Kaplan-Meier approach for each tumor type.

  17. Median Time to Death - Part 2 [Baseline up to end of treatment in Part 2 (maximum of 851 days)]

    Median time to death was analyzed by the Kaplan-Meier approach for each tumor type.

  18. Probability of Survival at 6 Months, 1 Year, and 2 Years - Part 2 [Baseline up to end of treatment in Part 2 (maximum of 851 days)]

    Probability of survival was calculated from the product-limit method.

  19. Trough PF-06801591 Concentrations (Ctrough) - Part 2 [Pre-dose on Day 1 of Cycles 2-6, 9, 12, 15, 18, 21, 24, and Follow-up Day 28 in Part 2]

    Trough PF-06801591 Concentrations (Ctrough) - Part 2. Ctrough was directly observed from data.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria (Part 2 Only):
  • Histological or cytological diagnosis of locally advanced or metastatic NSCLC or urothelial carcinoma who have progressed on or were intolerant to standard of care systemic therapy, or for whom standard of care systemic therapy was refused (refusal must be documented) or unavailable.

  • No prior treatment with anti-PD-1 or anti-PD-L1 therapy.

  • NSCLC patients whose tumor is not known to have ALK or EGFR mutations must have progressed on or after no more than 1 prior line of platinum-containing systemic therapy or were intolerant or refused standard of care systemic therapy.

  • NSCLC patients whose tumor is known to have ALK or EGFR mutation must have received prior systemic therapies that only include 1 or more lines of ALK or EGFR targeting drugs and chemotherapy limited to 1 line of a platinum-based regimen and they must have progressed on or after both types of therapies.

  • Urothelial carcinoma patients must have received up to 2 lines of prior systemic therapy and progressed on or after, experienced disease recurrence within 12 months of neoadjuvant or adjuvant treatment, were intolerant to, ineligible or refused platinum-containing systemic therapy. If urothelial cancer patients are treatment naïve and eligible for platinum-containing systemic therapy but are refusing platinum chemotherapy, they must also be documented to have previous PD-L1 high status.

  • Provide archived tumor tissue sample taken within the past 2 years or provide a fresh tumor biopsy sample.

  • At least one measurable lesion as defined by RECIST version 1.1.

  • Adequate renal, liver, thyroid and bone marrow function.

  • Performance status 0 or 1.

  • Patient is capable of receiving study treatment for at least 8 weeks.

Exclusion Criteria (Part 2 Only)

  • Active brain or leptomeningeal metastases.

  • Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy or prior allogeneic bone marrow or hematopoietic stem cell transplant.

  • Patients with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

  • Patients with a history of interstitial lung disease, non-infectious pneumonitis, or active pulmonary tuberculosis. Those with active lung infections requiring treatment are also excluded.

  • History of Grade ≥3 immune mediated AE (including AST/ALT elevations that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory agents, etc.) and required immunosuppressive therapy.

  • Active hepatitis B or C, HIV/AIDS.

  • Other potentially metastatic malignancy within past 5 years.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Clinical Research UnitLos AngelesCaliforniaUnited States90024
2Ronald Reagan Medical Center, Department of Radiological SciencesLos AngelesCaliforniaUnited States90095
3Ronald Reagan UCLA Medical Center, Drug Information CenterLos AngelesCaliforniaUnited States90095
4UCLA Hematology & Oncology ClinicLos AngelesCaliforniaUnited States90095
5Santa Monica UCLA Hematology & Oncology ClinicSanta MonicaCaliforniaUnited States90404
6Norton Cancer Institute, Multidisciplinary ClinicLouisvilleKentuckyUnited States40202
7Norton Cancer Institute, Norton Healthcare PavilionLouisvilleKentuckyUnited States40202
8Norton HospitalLouisvilleKentuckyUnited States40202
9Comprehensive Cancer Centers of NevadaLas VegasNevadaUnited States89169
10University of RochesterRochesterNew YorkUnited States14642
11UNC Hospitals, The University of North Carolina at Chapel HillChapel HillNorth CarolinaUnited States27599-7600
12Tennessee Oncology, PLLCDicksonTennesseeUnited States37055
13Tennessee Oncology, PLLCFranklinTennesseeUnited States37067
14Tennessee Oncology, PLLCGallatinTennesseeUnited States37066
15Tennessee Oncology, PLLCHermitageTennesseeUnited States37076
16Tennessee Oncology, PLLCLebanonTennesseeUnited States37090
17Tennessee Oncology, PLLCMurfreesboroTennesseeUnited States37129
18Tennessee Oncology, PLLCNashvilleTennesseeUnited States37203
19The Sarah Cannon Research InstituteNashvilleTennesseeUnited States37203
20Tennessee Oncology, PLLCNashvilleTennesseeUnited States37205
21Tennessee Oncology, PLLCNashvilleTennesseeUnited States37207
22Tennessee Oncology, PLLCNashvilleTennesseeUnited States37211
23Tennessee Oncology, PLLCShelbyvilleTennesseeUnited States37160
24Tennessee Oncology, PLLCSmyrnaTennesseeUnited States37167
25MHAT Uni Hospital OODPanagyurishtePazardzhikBulgaria4500
26Complex Oncology Center - Plovdiv EOODPlovdivBulgaria4000
27"MHAT for Women Health - Nadezhda" OODSofiaBulgaria1330
28SHATOD "Dr. Marko Antonov Markov - Varna" EOODVarnaBulgaria9002
29National Cancer CenterGoyang-siGyeonggi-doKorea, Republic of10408
30Seoul National University Bundang HospitalSeongnam-siGyeonggi-doKorea, Republic of13620
31The Catholic University of Korea, St. Vincent's HospitalSuwonGyeonggi-doKorea, Republic of16247
32Gachon University Gil Medical CenterIncheonKorea, Republic of21565
33Division of Medical Oncology, Severance Hospital, Yonsei University Health SystemSeoulKorea, Republic of03722
34Severance Hospital Yonsei University Health SystemSeoulKorea, Republic of03722
35Severance Hospital, Yonsei University Health SystemSeoulKorea, Republic of03722
36Asan Medical CenterSeoulKorea, Republic of05505
37Ulsan University HospitalUlsanKorea, Republic of44033
38Hospital Sultan IsmailJohor BahruJohorMalaysia81100
39University Malaya Medical CentreLembah PantaiKuala LumpurMalaysia59100
40Hospital Tengku Ampuan AfzanKuantanPahangMalaysia25100
41Clinical Research Centre(Crc), Hospital Umum SarawakKuchingSarawakMalaysia93586
42Szpitale Pomorskie Sp. z.o.o., Oddzial Onkologii i RadioterapiiGdyniaPoland81-519
43Regionalny Szpital Specjalistyczny im. dr. Wl. Bieganskiego w GrudziadzuGrudziadzPoland86-300
44Centrum Badan Klinicznych JCI Life Science ParkKrakowPoland30-348
45Mazowiecki Szpital Specjalistyczny im. Dr. Jozefa Psarskiego w Ostrolece, Osrodek OnkologicznyOstrolekaPoland07-410
46Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka ChopinaOtwockPoland05-400
47Centrum Onkologii-Instytut im.Marii Sklodowskiej-CurieWarszawaPoland02-781
48Sbhi "Lrcod"Vsevolozhsky DistrictLeningrad RegionRussian Federation188663
49SBHI ¨Saint-Petersburg clinical scientific practical center of specialized types ofPesochny VillageSaint-petersburgRussian Federation197758
50SBHI "ChRCCO and NM"ChelyabinskRussian Federation454087
51MROI n.a. P.A. Gertsen, filiation of FSBI "NMRC of radiology" MoH RussiaMoscowRussian Federation125284
52BHI of Omsk Region "Clinical Oncology Dispensary"OmskRussian Federation644013
53Joint Stock Company Current medical technologiesSaint-PetersburgRussian Federation190013
54Non-governmental Healthcare Institution ¨Railway Clinical Hospital of JSC ¨Russian Railways¨Saint-PetersburgRussian Federation195271
55SPb SBHI "City Clinical Oncology Dispensary"Saint-PetersburgRussian Federation197022
56SPb SBHI "City Clinical Oncology Dispensary"Saint-PetersburgRussian Federation198255
57Joint-Stock Company Current medical technologiesSt. PetersburgRussian Federation190121
58SBHI YaR ¨Regional clinical oncology hospital¨YaroslavlRussian Federation150054
59Communal Non-profit Institution "City Clinical Hospital #4" of Dnipro City Council, Department ofDniproUkraine49102
60Communal non-Commercial Enterprise "Prykarpatski Clinical Oncological Center of Ivano-Ivano-FrankivskUkraine79018
61Grigoriev Radiological Institute of the National Academy of Medical Sciences of Ukraine,KharkivUkraine61024
62Communal Non-profit Institution of Kharkiv Regional Council "Regional Clinical Specialized HealthKharkivUkraine61166
63"Specialized Clinic "Prognosis Optima" LLCKyivUkraine03126
64Communal noncommercial enterprise Sumy regional Rada Sumy regional clinical oncologic dispensary,SumyUkraine40030
65Communal Non-profit Institution "Central City Clinical Hospital" of Uzhhorod City Council,UzhhorodUkraine88000
66Vinnytsia Regional Clinical Oncological HospitalVinnytsiaUkraine21029
67Communal Institution ¨Zaporizhzhya Regional Clinical Oncological Dispensary¨ZaporizhzhyaUkraine69040

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02573259
Other Study ID Numbers:
  • B8011001
  • 2016-003314-27
First Posted:
Oct 9, 2015
Last Update Posted:
Dec 13, 2021
Last Verified:
Oct 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment DetailA total of 147 participants were enrolled in this study, and 146 participants received study treatment. For Part 1, 40 participants were enrolled and treated. For Part 2, 107 participants were enrolled including 68 participants with non small cell lung cancer (NSCLC) and 39 participants with urothelial carcinoma (UC), and 106 participants received study treatment.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Period Title: Overall Study
STARTED2887156839
Treated2887156838
COMPLETED10212105
NOT COMPLETED1866135834

Baseline Characteristics

Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UCTotal
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)Total of all reporting groups
Overall Participants2887156838146
Age, Customized (Number) [Number]
18-44 Years
0
0%
0
0%
1
12.5%
1
14.3%
0
0%
1
1.5%
1
2.6%
4
2.7%
45-64 Years
1
50%
3
37.5%
5
62.5%
3
42.9%
10
66.7%
28
41.2%
16
42.1%
66
45.2%
>=65 Years
1
50%
5
62.5%
2
25%
3
42.9%
5
33.3%
39
57.4%
21
55.3%
76
52.1%
Sex: Female, Male (Count of Participants)
Female
2
100%
6
75%
5
62.5%
4
57.1%
11
73.3%
15
22.1%
13
34.2%
56
38.4%
Male
0
0%
2
25%
3
37.5%
3
42.9%
4
26.7%
53
77.9%
25
65.8%
90
61.6%
Race/Ethnicity, Customized (Number) [Number]
White
2
100%
7
87.5%
7
87.5%
4
57.1%
12
80%
50
73.5%
30
78.9%
112
76.7%
Black or African American
0
0%
0
0%
0
0%
1
14.3%
2
13.3%
0
0%
0
0%
3
2.1%
Asian
0
0%
0
0%
0
0%
2
28.6%
1
6.7%
18
26.5%
8
21.1%
29
19.9%
Other
0
0%
1
12.5%
1
12.5%
0
0%
0
0%
0
0%
0
0%
2
1.4%

Outcome Measures

1. Primary Outcome
TitlePercentage of Participants With Dose-Limiting Toxicities (DLT) - Part 1
DescriptionDLT was defined as any of the following drug-related adverse events (AEs) occurring during the first cycle (21 days for IV dosing, 28 days for SC dosing) in Part 1: Grade 5 AE; Grade 4 neutropenia lasting >5 days from initiation of granulocyte colony stimulating factor; Grade 4 thrombocytopenia with bleeding; Platelet transfusion requirement or a platelet count <10,000/uL; Grade 4 non-hematologic AE; Grade 3 AE lasting >7 days despite optimal supportive care; Grade 3 central nervous system AE regardless of duration; met criteria for drug induced liver injury. Severity of AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
Time FrameCycle 1 in Part 1 (21 days for IV administration of PF-06801591; 28 days for SC administration of PF-06801591)

Outcome Measure Data

Analysis Population Description
DLT analysis population included all enrolled participants who received at least 1 dose of study treatment and who did not have major treatment deviations during Cycle 1.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants288715
Number [Percentage of Participants]
0
0%
0
0%
0
0%
0
0%
0
0%
2. Primary Outcome
TitleNumber of Participants With All-Causality Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
DescriptionAE = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of severity were defined by CTCAE v4.03. Grades of severity were defined by CTCAE v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
Time FrameBaseline up to 28 days after last dose of study treatment (maximum of 1634 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants who received at least 1 dose of study medication.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants2887156838
Participants with AEs
2
100%
7
87.5%
8
100%
7
100%
15
100%
62
91.2%
36
94.7%
Participants with SAEs
1
50%
3
37.5%
3
37.5%
3
42.9%
3
20%
18
26.5%
13
34.2%
Participants with maximum Grade 3 or 4 AEs
2
100%
2
25%
3
37.5%
2
28.6%
4
26.7%
18
26.5%
13
34.2%
Participants with maximum Grade 5 AEs
0
0%
1
12.5%
1
12.5%
2
28.6%
0
0%
8
11.8%
5
13.2%
3. Primary Outcome
TitleNumber of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
DescriptionTreatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AEs and SAEs were determined by the investigator. Grades of severity were defined by CTCAE v4.03. Grades of severity were defined by CTCAE v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
Time FrameBaseline up to 28 days after last dose of study treatment (maximum of 1634 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants who received at least 1 dose of study medication.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants2887156838
Participants with AEs
2
100%
6
75%
7
87.5%
6
85.7%
13
86.7%
42
61.8%
17
44.7%
Participants with SAEs
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
3
7.9%
Participants with maximum of Grade 3 or 4 AEs
1
50%
1
12.5%
1
12.5%
1
14.3%
1
6.7%
9
13.2%
5
13.2%
Participants with maximum of Grade 5 AEs
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
4. Primary Outcome
TitleNumber of Participants With Laboratory Test Abnormalities - Part 1 and Part 2
DescriptionFollowing parameters were analyzed for laboratory examination: hematology (anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased); chemistries (increase of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood bilirubin, CPK, creatinine, gamma-glutamyl transferase [GGT], lipase, and serum amylase); urinalysis (proteinuria); coagulation (activated partial thromboplastin time prolonged, international normalized ratio [INR] increased). Grades of severity were defined by CTCAE v4.03. Grade 0 = No Change from normal or reference range (this grade is not included in the CTCAE v4.03 document but may used in certain circumstances). Grade 1 = mild adverse event (AE). Grade 2 = moderate AE; Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
Time FrameBaseline up to 28 days after last dose of study treatment (maximum of 1634 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants who received at least 1 dose of study medication.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants2787156838
Grade 0
0
0%
2
25%
1
12.5%
1
14.3%
1
6.7%
16
23.5%
6
15.8%
Grade 1
1
50%
1
12.5%
4
50%
5
71.4%
5
33.3%
38
55.9%
16
42.1%
Grade 2
1
50%
4
50%
3
37.5%
1
14.3%
8
53.3%
13
19.1%
9
23.7%
Grade 3
0
0%
0
0%
0
0%
0
0%
1
6.7%
1
1.5%
7
18.4%
Grade 4
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 0
2
100%
7
87.5%
8
100%
7
100%
15
100%
60
88.2%
35
92.1%
Grade 1
0
0%
0
0%
0
0%
0
0%
0
0%
7
10.3%
3
7.9%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
0
0%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 4
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 0
0
0%
3
37.5%
0
0%
1
14.3%
9
60%
27
39.7%
20
52.6%
Grade 1
0
0%
0
0%
2
25%
1
14.3%
2
13.3%
21
30.9%
11
28.9%
Grade 2
2
100%
2
25%
6
75%
4
57.1%
1
6.7%
15
22.1%
5
13.2%
Grade 3
0
0%
1
12.5%
0
0%
1
14.3%
3
20%
5
7.4%
2
5.3%
Grade 4
0
0%
1
12.5%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
2
100%
7
87.5%
8
100%
7
100%
14
93.3%
63
92.6%
37
97.4%
Grade 1
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 2
0
0%
0
0%
0
0%
0
0%
1
6.7%
5
7.4%
1
2.6%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 4
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 0
2
100%
6
75%
7
87.5%
5
71.4%
13
86.7%
61
89.7%
35
92.1%
Grade 1
0
0%
1
12.5%
1
12.5%
2
28.6%
1
6.7%
4
5.9%
0
0%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
2
2.9%
3
7.9%
Grade 3
0
0%
0
0%
0
0%
0
0%
1
6.7%
0
0%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
0
0%
Grade 0
1
50%
7
87.5%
7
87.5%
6
85.7%
12
80%
56
82.4%
33
86.8%
Grade 1
1
50%
0
0%
1
12.5%
1
14.3%
3
20%
12
17.6%
5
13.2%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
1
50%
5
62.5%
5
62.5%
3
42.9%
10
66.7%
62
91.2%
34
89.5%
Grade 1
1
50%
1
12.5%
3
37.5%
4
57.1%
4
26.7%
5
7.4%
3
7.9%
Grade 2
0
0%
1
12.5%
0
0%
0
0%
1
6.7%
0
0%
1
2.6%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
2
100%
7
87.5%
8
100%
4
57.1%
14
93.3%
45
66.2%
31
81.6%
Grade 1
0
0%
0
0%
0
0%
3
42.9%
1
6.7%
19
27.9%
3
7.9%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
3
7.9%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
3
4.4%
1
2.6%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
1
50%
4
50%
5
62.5%
4
57.1%
6
40%
36
52.9%
21
55.3%
Grade 1
0
0%
2
25%
3
37.5%
2
28.6%
7
46.7%
22
32.4%
11
28.9%
Grade 2
1
50%
1
12.5%
0
0%
0
0%
2
13.3%
7
10.3%
4
10.5%
Grade 3
0
0%
0
0%
0
0%
1
14.3%
0
0%
3
4.4%
2
5.3%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
0
0%
5
62.5%
7
87.5%
5
71.4%
11
73.3%
44
64.7%
23
60.5%
Grade 1
2
100%
2
25%
1
12.5%
1
14.3%
4
26.7%
17
25%
13
34.2%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
5
7.4%
1
2.6%
Grade 3
0
0%
0
0%
0
0%
1
14.3%
0
0%
1
1.5%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.6%
Grade 0
1
50%
7
87.5%
7
87.5%
6
85.7%
13
86.7%
58
85.3%
34
89.5%
Grade 1
0
0%
0
0%
1
12.5%
0
0%
1
6.7%
6
8.8%
3
7.9%
Grade 2
1
50%
0
0%
0
0%
0
0%
1
6.7%
3
4.4%
1
2.6%
Grade 3
0
0%
0
0%
0
0%
1
14.3%
0
0%
1
1.5%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
3
150%
Grade 1
0
0%
Grade 2
0
0%
Grade 3
0
0%
Grade 4
0
0%
Grade 0
0
0%
0
0%
3
37.5%
0
0%
13
86.7%
58
85.3%
2
5.3%
Grade 1
1
50%
6
75%
4
50%
7
100%
1
6.7%
6
8.8%
30
78.9%
Grade 2
1
50%
1
12.5%
1
12.5%
0
0%
1
6.7%
3
4.4%
5
13.2%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
1
2.6%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
0
0%
0
0%
0
0%
Grade 1
1
50%
2
25%
1
12.5%
Grade 2
0
0%
1
12.5%
0
0%
Grade 3
0
0%
1
12.5%
1
12.5%
Grade 4
0
0%
0
0%
0
0%
Grade 0
2
100%
7
87.5%
8
100%
7
100%
13
86.7%
51
75%
31
81.6%
Grade 1
0
0%
0
0%
0
0%
0
0%
1
6.7%
15
22.1%
5
13.2%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
0
0%
Grade 3
0
0%
0
0%
0
0%
0
0%
1
6.7%
0
0%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
2
5.3%
Grade 0
2
100%
5
62.5%
8
100%
6
85.7%
14
93.3%
24
35.3%
12
31.6%
Grade 1
0
0%
0
0%
0
0%
0
0%
0
0%
31
45.6%
21
55.3%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
10
14.7%
4
10.5%
Grade 3
0
0%
2
25%
0
0%
0
0%
1
6.7%
3
4.4%
1
2.6%
Grade 4
0
0%
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
Grade 0
2
100%
6
75%
7
87.5%
7
100%
15
100%
48
70.6%
27
71.1%
Grade 1
0
0%
0
0%
1
12.5%
0
0%
0
0%
8
11.8%
6
15.8%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
11
16.2%
3
7.9%
Grade 3
0
0%
1
12.5%
0
0%
0
0%
0
0%
1
1.5%
2
5.3%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
1
50%
7
87.5%
7
87.5%
5
71.4%
15
100%
55
80.9%
35
92.1%
Grade 1
1
50%
0
0%
1
12.5%
2
28.6%
0
0%
6
8.8%
3
7.9%
Grade 2
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
7
10.3%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
2
100%
5
62.5%
8
100%
6
85.7%
13
86.7%
51
75%
35
92.1%
Grade 1
0
0%
2
25%
0
0%
1
14.3%
2
13.3%
8
11.8%
2
5.3%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
7
10.3%
0
0%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
2
2.9%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.6%
Grade 0
1
50%
5
62.5%
5
62.5%
3
42.9%
10
66.7%
40
58.8%
23
60.5%
Grade 1
0
0%
2
25%
2
25%
4
57.1%
2
13.3%
18
26.5%
11
28.9%
Grade 2
1
50%
0
0%
1
12.5%
0
0%
2
13.3%
10
14.7%
4
10.5%
Grade 3
0
0%
0
0%
0
0%
0
0%
1
6.7%
0
0%
0
0%
Grade 4
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 0
1
50%
6
75%
5
62.5%
5
71.4%
13
86.7%
49
72.1%
30
78.9%
Grade 1
1
50%
1
12.5%
3
37.5%
2
28.6%
1
6.7%
12
17.6%
7
18.4%
Grade 2
0
0%
0
0%
0
0%
0
0%
1
6.7%
7
10.3%
0
0%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.6%
Grade 0
2
100%
7
87.5%
8
100%
7
100%
15
100%
60
88.2%
32
84.2%
Grade 1
0
0%
0
0%
0
0%
0
0%
0
0%
8
11.8%
6
15.8%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
1
50%
7
87.5%
5
62.5%
6
85.7%
10
66.7%
61
89.7%
33
86.8%
Grade 1
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 2
1
50%
0
0%
3
37.5%
1
14.3%
4
26.7%
7
10.3%
3
7.9%
Grade 3
0
0%
0
0%
0
0%
0
0%
1
6.7%
0
0%
2
5.3%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
2
100%
6
75%
7
87.5%
7
100%
8
53.3%
42
61.8%
29
76.3%
Grade 1
0
0%
1
12.5%
1
12.5%
0
0%
5
33.3%
14
20.6%
8
21.1%
Grade 2
0
0%
0
0%
0
0%
0
0%
2
13.3%
8
11.8%
1
2.6%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
4
5.9%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
0
0%
4
50%
7
87.5%
5
71.4%
8
53.3%
45
66.2%
25
65.8%
Grade 1
0
0%
2
25%
1
12.5%
1
14.3%
5
33.3%
19
27.9%
10
26.3%
Grade 2
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 3
2
100%
0
0%
0
0%
1
14.3%
2
13.3%
3
4.4%
2
5.3%
Grade 4
0
0%
1
12.5%
0
0%
0
0%
0
0%
1
1.5%
1
2.6%
Grade 0
1
50%
5
62.5%
6
75%
7
100%
15
100%
56
82.4%
27
71.1%
Grade 1
0
0%
0
0%
0
0%
0
0%
0
0%
3
4.4%
7
18.4%
Grade 2
1
50%
2
25%
2
25%
0
0%
0
0%
7
10.3%
4
10.5%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
0
0%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
2
100%
4
50%
5
62.5%
7
100%
13
86.7%
50
73.5%
23
60.5%
Grade 1
0
0%
3
37.5%
1
12.5%
0
0%
0
0%
11
16.2%
7
18.4%
Grade 2
0
0%
0
0%
1
12.5%
0
0%
0
0%
4
5.9%
3
7.9%
Grade 3
0
0%
0
0%
1
12.5%
0
0%
1
6.7%
1
1.5%
3
7.9%
Grade 4
0
0%
0
0%
0
0%
0
0%
1
6.7%
2
2.9%
1
2.6%
Grade 0
1
50%
6
75%
7
87.5%
6
85.7%
13
86.7%
45
66.2%
23
60.5%
Grade 1
1
50%
1
12.5%
1
12.5%
0
0%
1
6.7%
16
23.5%
10
26.3%
Grade 2
0
0%
0
0%
0
0%
1
14.3%
0
0%
4
5.9%
2
5.3%
Grade 3
0
0%
0
0%
0
0%
0
0%
1
6.7%
3
4.4%
3
7.9%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
0
0%
5
62.5%
4
50%
1
14.3%
9
60%
46
67.6%
15
39.5%
Grade 1
1
50%
2
25%
3
37.5%
3
42.9%
6
40%
15
22.1%
17
44.7%
Grade 2
1
50%
0
0%
1
12.5%
2
28.6%
0
0%
5
7.4%
5
13.2%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2.6%
Grade 4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Grade 0
1
50%
6
75%
5
62.5%
4
57.1%
11
73.3%
44
64.7%
19
50%
Grade 1
1
50%
1
12.5%
3
37.5%
3
42.9%
4
26.7%
19
27.9%
15
39.5%
Grade 2
0
0%
0
0%
0
0%
0
0%
0
0%
4
5.9%
3
7.9%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
1
1.5%
1
2.6%
Grade 4
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
Grade 0
2
100%
5
62.5%
6
75%
4
57.1%
12
80%
39
57.4%
31
81.6%
Grade 1
0
0%
2
25%
1
12.5%
3
42.9%
3
20%
25
36.8%
4
10.5%
Grade 2
0
0%
0
0%
1
12.5%
0
0%
0
0%
1
1.5%
1
2.6%
Grade 3
0
0%
0
0%
0
0%
0
0%
0
0%
3
4.4%
0
0%
Grade 4
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
5. Primary Outcome
TitleObjective Response Rate (ORR) Based on RECIST Version 1.1 - Part 2
DescriptionORR was defined as percentage of participants with confirmed objective response (OR) of complete response (CR) and partial response (PR) based on RECIST version 1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis < 10 mm). All target lesions must be assessed. PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.
Time FrameBaseline up to end of treatment in Part 2 (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants6738
Number (95% Confidence Interval) [Percentage]
16.4
18.4
6. Primary Outcome
TitleObjective Response Rate (ORR) Based on Immune Related RECIST (irRECIST) - Part 2
DescriptionORR was defined as percentage of participants with objective response (OR) of complete response (CR) and partial response (PR) based on irRECIST. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis < 10 mm). All target lesions must be assessed. PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.
Time FrameBaseline up to end of treatment in Part 2 (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants6738
Number (95% Confidence Interval) [Percentage of Participants]
19.4
970%
21.1
263.8%
7. Secondary Outcome
TitleMaximum Plasma Concentration (Cmax) of PF-06801591 - Part 1
DescriptionCmax was the maximum concentration after dose administration observed directly from the data.
Time FramePre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants treated who were evaluable for this outcome measure.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants288715
Cycle 1 Day 1
NA
(NA)
21.52
(23)
69.63
(28)
217.2
(36)
21.24
(50)
Cycle 4 Day 1
NA
(NA)
30.10
(16)
86.34
(52)
402.6
(42)
56.48
(29)
8. Secondary Outcome
TitleAUClast of PF-06801591 in Part 1.
DescriptionArea Under the Concentration Versus Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point Prior to the Next Dose (AUClast) of PF-06801591 - Part 1
Time FramePre-dose, 1 and 24 hours post dose on Cycle 1 Day 1 in Part 1

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants treated who were evaluable for this outcome measure.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants277715
Geometric Mean (Geometric Coefficient of Variation) [ug*hr/mL]
NA
(NA)
4700
(41)
14770
(27)
46780
(49)
9923
(65)
9. Secondary Outcome
TitleClearance (CL) of PF-06801591 - Part 1
DescriptionCL for IV dosing. CL was calculated by dose / AUCtau for Cycles 1 and 4 IV dosing. AUCtau was defined as area under the serum concentration time profile from time zero to time tau, the dosing interval, where tau = 504 hours for every 3 weeks (Q3W) IV dosing reporting arm.
Time FramePre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants treated who were evaluable for this outcome measure.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)
Measure Participants2234
Cycle 1 Day 1
NA
(NA)
Cycle 4 Day 1
NA
(NA)
NA
(NA)
0.006045
(57)
0.004984
(14)
10. Secondary Outcome
TitleVolume of Distribution at Steady State (Vss) of PF-06801591 - Part 1
DescriptionSteady state volume of distribution of PF-0680159 for IV dosing. Vss was calculated by CL*MRT. CL was the clearance for IV dosing. MRT was the mean residence time calculated for a single IV dose as AUMCinf/AUCinf - (DOF/2). AUMCinf was the area under the moment curve from time 0 extrapolated to infinity. DOF was the duration of infusion. AUCinf was the area under the serum concentration time profile from time 0 extrapolated to infinity.
Time FramePre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1

Outcome Measure Data

Analysis Population Description
The PK parameter analysis population was defined as all enrolled participants in Part 1 who received study drug following IV administration and had sufficient information to estimate at least 1 of the pharmacokinetic (PK) parameters of interest. Number of participants analyzed represents the total number of participants in each treatment group in the PK parameter analysis population. Number analyzed represents the number of participants who had reportable parameter values of Vss.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)
Measure Participants2887
Cycle 1 Day 1
NA
(NA)
11. Secondary Outcome
TitleAccumulation Ratio (Rac) of PF-06801591 - Part 1
DescriptionRac was calculated by (Cycle 4 AUCtau) / (Cycle 1 AUCtau). AUCtau was Area under the serum concentration time profile from time zero to time tau, the dosing interval, where tau = 504 hours for Q3W IV dosing and tau = 672 hours for every 4 weeks (Q4W) SC dosing.
Time FramePre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants treated who were evaluable for this outcome measure.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants22243
Geometric Mean (Geometric Coefficient of Variation) [Ratio]
NA
(NA)
NA
(NA)
NA
(NA)
2.360
(12)
2.073
(31)
12. Secondary Outcome
TitleTerminal Elimination Half-Life (t1/2) of PF-06801591 - Part 1
Descriptiont1/2 was calculated by Loge(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.
Time FramePre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1

Outcome Measure Data

Analysis Population Description
The PK parameter analysis population was defined as all enrolled participants in Part 1 who received study drug following IV or SC administration and had sufficient information to estimate at least 1 of the PK parameters of interest. Number of participants analyzed represents the total number of participants in each treatment group in the PK parameter analysis population. Number analyzed represents the number of participants who had reportable parameter values of t1/2.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants288715
Cycle 1 Day 1
NA
(NA)
Cycle 4 Day 1
NA
(NA)
13. Secondary Outcome
TitleNumber of Participants With Anti-Drug Antibody (ADA) Against PF-06801591 - Part 1 and Part 2
DescriptionNumber of participants with ADA positive against PF-06801591 after IV and SC dosing - Part 1 and Part 2. A participant was ADA positive if (1) baseline titer was missing or negative and participant had ≥ 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ≥ 0.602 in titer from baseline in ≥ 1 post-treatment sample (treatment-boosted). Participants who were ADA positive at baseline but did not become boosted post-treatment were considered as ADA negative.
Time FrameBaseline up to end of treatment (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all participants who received at least 1 dose of study treatment and had at least 1 post-treatment ADA result.
Arm/Group TitlePart 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UCPart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)
Arm/Group DescriptionParticipants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)Participants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)
Measure Participants1464372676
Count of Participants [Participants]
1
50%
5
62.5%
3
37.5%
1
14.3%
1
6.7%
0
0%
0
0%
14. Secondary Outcome
TitleNumber of Participants With Neutralizing Antibodies (NAb) Positive Against PF-06801591 - Part 1 and Part 2
DescriptionNumber of participants with NAb positive against PF-06801591 after IV and SC dosing - Part 1 and Part 2. A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥ 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ≥ 0.602 in titer from baseline in ≥ 1 post-treatment sample (treatment-boosted). Participants who were NAb positive at baseline but did not become boosted post-treatment were considered as NAb negative.
Time FrameBaseline up to end of treatment (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all participants who received at least 1 dose of study treatment and had at least 1 post-treatment ADA result. NAb-negative participants included participants who were ADA negative or ADA-positive participants who tested negative in the NAb assay.
Arm/Group TitlePart 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UCPart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)
Arm/Group DescriptionParticipants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)Participants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)
Measure Participants1464372676
Count of Participants [Participants]
0
0%
3
37.5%
1
12.5%
0
0%
0
0%
0
0%
0
0%
15. Secondary Outcome
TitlePercentage of Baseline PD-1 Receptor Occupancy (RO) by PF-06801591 - Part 1
DescriptionPD-1 RO by sasanlimab was measured by the reduction of free receptor on the surface of CD8+ effector cells (CD3+, CD4-, CD8+, CD45RA+, CCR7-, CD279+) and CD8+ effector memory cells (CD3+, CD4-, CD8+, CD45RA-, CCR7-, CD279+) presented in pre- and postdose whole blood samples by flow cytometry. Percentage of baseline (ie, normalized change from baseline) PD-1 RO were calculated as [(percentage of cells at Cycle X Day X)/(percentage of cells at baseline)]*100, and are reported for this outcome measure. Baseline was defined as the most recent non-missing value prior to dosing.
Time FrameBaseline, Days 1, 8, 15, 21 of Cycle 1, Day 1 of Cycles 2, 3, 5, Days 1, 15, 21 of Cycle 4, and end of treatment (EOT) in Part 1 (cycle = 21 days for IV dosing; cycle = 28 days for SC dosing)

Outcome Measure Data

Analysis Population Description
Analysis population included all enrolled participants with at least 1 of the pharmacodynamic/biomarker parameters evaluated at pre- and/or post dose.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants287715
Cycle 1 Day 1
0.00
0.00
0.56
0.02
0.32
Cycle 1 Day 8
0.00
0.00
0.00
0.00
0.00
Cycle 1 Day 15
0.00
0.00
0.00
0.00
0.57
Cycle 1 Day 21
0.00
Cycle 2 Day 1
1.48
0.04
0.82
0.00
0.00
Cycle 3 Day 1
0.00
0.00
0.47
0.00
0.00
Cycle 4 Day 1
0.80
0.00
0.05
0.00
0.00
Cycle 4 Day 15
0.00
0.00
0.00
0.00
0.00
Cycle 4 Day 21
1.31
Cycle 5 Day 1
0.00
0.00
0.00
0.00
0.00
EOT
0.00
0.00
0.00
0.17
16. Secondary Outcome
TitleNumber of Participants Achieving Objective Response (OR) Based on RECIST Version 1.1 - Part 1
DescriptionNumber of participants achieving confirmed OR based on RECIST version 1.1 in Part 1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis < 10 mm). All target lesions must be assessed. PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.
Time FrameBaseline up to end of treatment in Part 1 (maximum of 1606 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants278715
Count of Participants [Participants]
1
50%
2
25%
1
12.5%
2
28.6%
1
6.7%
17. Secondary Outcome
TitleNumber of Participants Achieving Objective Response (OR) Based on irRECIST - Part 1
DescriptionNumber of participants achieving confirmed OR based on irRECIST in Part 1. OR = irCR + irPR. Overall immune related complete response (irCR) was defined as complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. Overall immune related partial response (irPR) was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases >=30%.
Time FrameBaseline up to end of treatment in Part 1 (maximum of 1606 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)
Measure Participants278715
Count of Participants [Participants]
1
50%
2
25%
1
12.5%
2
28.6%
1
6.7%
18. Secondary Outcome
TitleProgression-Free Survival (PFS) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2
DescriptionPFS was defined as the time from initiation of study intervention to first documentation of tumor progression or to death due to any cause, whichever occurred first. PFS was analyzed by the Kaplan-Meier approach for each tumor type. As this outcome measure was a secondary endpoint defined in the protocol to investigate preliminary signal of efficacy, the results were analyzed and are reported for Part 1 dose-escalation groups combined to provide more statistically meaningful results, instead of results analyzed by dose level with very limited number of participants in each group.
Time FrameBaseline up to end of treatment (maximum of 1606 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 1: PF-06801591 0.5-10 mg/kg (Intravenously [IV])Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionThis was a combined group of PF-06801591 0.5, 1, 3, and 10 mg/kg (IV) in Part 1. Participants received PF-06801591 0.5, 1, 3, or 10 mg/kg IV every 3 weeks for 21-day cycles. (up to a maximum of 233 weeks).Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants24156738
RECIST v1.1
4.7
3.0
3.7
2.9
irRECIST
4.9
4.5
5.5
3.8
19. Secondary Outcome
TitleDuration of Stable Disease (DOSD) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2
DescriptionDOSD was analyzed by the Kaplan-Meier approach for each tumor type. Stable disease (SD) was defined as not qualifying for complete response (CR), partial response (PR), or progression. All target lesions must have been assessed. Stable could follow PR only in the rare case that the sum increased by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer held. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). All target lesions must have been assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed.
Time FrameBaseline up to end of treatment (maximum of 1606 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants123252412
RECIST v1.1
NA
NA
24.3
5.7
6.0
6.5
8.5
irRECIST
NA
NA
29.0
5.7
13.7
7.5
14.5
20. Secondary Outcome
TitleDuration of Response (DOR) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2
DescriptionDOR was defined as the time from start date (which was the date of first documentation of PR or CR) to date of first documentation of objective progression or death. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. As this outcome measure was a secondary endpoint defined in the protocol to investigate preliminary signal of efficacy, the results were analyzed and are reported for Part 1 dose-escalation groups combined to provide more statistically meaningful results, instead of results analyzed by dose level with very limited number of participants in each group.
Time FrameBaseline up to end of treatment (maximum of 1606 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death. DOR was only applicable to those participants with an objective response.
Arm/Group TitlePart 1: PF-06801591 0.5-10 mg/kg (Intravenously [IV])Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionThis was a combined group of PF-06801591 0.5, 1, 3, and 10 mg/kg (IV) in Part 1. Participants received PF-06801591 0.5, 1, 3, or 10 mg/kg IV every 3 weeks for 21-day cycles. (up to a maximum of 233 weeks).Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants61138
RECIST v1.1
9.7
NA
21.8
13.9
irRECIST
13.0
NA
22.1
NA
21. Secondary Outcome
TitleTime to Response (TTR) Based on RECIST Version 1.1 - Part 2
DescriptionTTR was the time to confirmed or unconfirmed complete response (CR) or partial response (PR) based on investigator assessment per RECIST v1.1 by tumor type. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). All target lesions must have been assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed.
Time FrameBaseline up to end of treatment in Part 2 (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants148
Median (Full Range) [Months]
2.71
2.33
22. Secondary Outcome
TitleTime to Progression (TTP) Based on RECIST Version 1.1 and irRECIST - Part 2
DescriptionTTP was the time to objective progression. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. TTP was analyzed by the Kaplan-Meier approach for each tumor type.
Time FrameBaseline up to end of treatment in Part 2 (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants6738
RECIST v1.1
3.7
3.7
irRECIST
6.5
8.5
23. Secondary Outcome
TitleMedian Time to Death - Part 2
DescriptionMedian time to death was analyzed by the Kaplan-Meier approach for each tumor type.
Time FrameBaseline up to end of treatment in Part 2 (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.
Arm/Group TitlePart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants6839
Median (95% Confidence Interval) [Months]
14.7
10.9
24. Secondary Outcome
TitleProbability of Survival at 6 Months, 1 Year, and 2 Years - Part 2
DescriptionProbability of survival was calculated from the product-limit method.
Time FrameBaseline up to end of treatment in Part 2 (maximum of 851 days)

Outcome Measure Data

Analysis Population Description
Analysis population included all the randomized participants who received PF-06801591 and had at least 1 post-dose concentration measurement above the lower limit of quantification (LLQ).
Arm/Group TitlePart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants6839
6 Months
0.773
0.711
1 Year
0.547
0.471
2 Years
0.403
0.286
25. Secondary Outcome
TitleTrough PF-06801591 Concentrations (Ctrough) - Part 2
DescriptionTrough PF-06801591 Concentrations (Ctrough) - Part 2. Ctrough was directly observed from data.
Time FramePre-dose on Day 1 of Cycles 2-6, 9, 12, 15, 18, 21, 24, and Follow-up Day 28 in Part 2

Outcome Measure Data

Analysis Population Description
Analysis population included all participants who received PF-06801591, had no protocol deviations affecting the pharmacokinetics (PK) assessment, and had at least 1 post-dose concentration measurement above lower limit of quantification.
Arm/Group TitlePart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UC
Arm/Group DescriptionParticipants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)
Measure Participants6839
Cycle 2 Day 1
14.97
(48)
14.34
(73)
Cycle 3 Day 1
22.54
(37)
20.15
(84)
Cycle 4 Day 1
23.55
(53)
23.77
(60)
Cycle 5 Day 1
23.58
(41)
19.32
(186)
Cycle 6 Day 1
29.67
(36)
17.13
(249)
Cycle 9 Day 1
29.01
(36)
29.88
(30)
Cycle 12 Day 1
34.29
(16)
12.74
(770)
Cycle 15 Day 1
40.90
(22)
22.10
(56)
Cycle 18 Day 1
35.09
(25)
20.17
(75)
Cycle 21 Day 1
27.16
(25)
22.11
(55)
Cycle 24 Day 1
30.81
(16)
38.02
(38)
Follow-up Day 28
43.62
(33)
35.17
(32)

Adverse Events

Time FrameBaseline up to 28 days after last dose of study drug (up to a maximum of 237 weeks).
Adverse Event Reporting Description The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Arm/Group TitlePart 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 1: PF-06801591 IV TotalPart 1: PF-06801591 IV and SC TotalPart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UCPart 2: PF-06801591 NSCLC and UC Total
Arm/Group DescriptionParticipants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)Participants received PF-06801591 IV every 3 weeks for 21-day cycles in Part 1. (up to a maximum of of 233 weeks)Participants received PF-06801591 IV every 3 weeks for 21-day cycles or SC every 4 weeks for 28-day cycles in Part 1. (up to a maximum of 233 weeks)Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)Participants with NSCLC or UC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles in Part 2. (up to a maximum of 126 weeks)
All Cause Mortality
Part 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 1: PF-06801591 IV TotalPart 1: PF-06801591 IV and SC TotalPart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UCPart 2: PF-06801591 NSCLC and UC Total
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/2 (50%) 6/8 (75%) 5/8 (62.5%) 6/7 (85.7%) 10/15 (66.7%) 18/25 (72%) 28/40 (70%) 33/68 (48.5%) 21/38 (55.3%) 54/106 (50.9%)
Serious Adverse Events
Part 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 1: PF-06801591 IV TotalPart 1: PF-06801591 IV and SC TotalPart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UCPart 2: PF-06801591 NSCLC and UC Total
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/2 (50%) 3/8 (37.5%) 3/8 (37.5%) 3/7 (42.9%) 3/15 (20%) 10/25 (40%) 13/40 (32.5%) 18/68 (26.5%) 13/38 (34.2%) 31/106 (29.2%)
Blood and lymphatic system disorders
Anaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
Cardiac disorders
Arrhythmia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Atrial fibrillation0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Cardiac failure0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Cardiogenic shock0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Gastrointestinal disorders
Diarrhoea0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Dysphagia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Enteritis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Gastric ulcer haemorrhage0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Intestinal obstruction0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Small intestinal obstruction0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Upper gastrointestinal haemorrhage1/2 (50%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
General disorders
Disease progression0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 2/7 (28.6%) 0/15 (0%) 4/25 (16%) 4/40 (10%) 3/68 (4.4%) 2/38 (5.3%) 5/106 (4.7%)
Mucosal ulceration0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Multiple organ dysfunction syndrome0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Non-cardiac chest pain0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Infections and infestations
Bronchitis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Pneumonia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Postoperative wound infection0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Pyelonephritis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Sepsis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Urinary tract infection0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Urosepsis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Injury, poisoning and procedural complications
Skin laceration0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Investigations
Transaminases increased0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Metabolism and nutrition disorders
Dehydration0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Musculoskeletal and connective tissue disorders
Muscular weakness0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Rotator cuff syndrome0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Lung neoplasm malignant0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Neoplasm progression0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Nervous system disorders
Cerebral infarction0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Cognitive disorder0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Spinal cord compression0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Renal and urinary disorders
Acute kidney injury0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Hydronephrosis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Haemoptysis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Hypoxia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Pneumonitis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Pneumothorax0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Pulmonary embolism0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Other (Not Including Serious) Adverse Events
Part 1: PF-06801591 0.5 mg/kg (Intravenously [IV])Part 1: PF-06801591 1 mg/kg (IV)Part 1: PF-06801591 3 mg/kg (IV)Part 1: PF-06801591 10 mg/kg (IV)Part 1: PF-06801591 300 mg (Subcutaneously [SC])Part 1: PF-06801591 IV TotalPart 1: PF-06801591 IV and SC TotalPart 2: PF-06801591 300 mg (SC) for NSCLCPart 2: PF-06801591 300 mg (SC) for UCPart 2: PF-06801591 NSCLC and UC Total
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total2/2 (100%) 7/8 (87.5%) 8/8 (100%) 7/7 (100%) 15/15 (100%) 24/25 (96%) 39/40 (97.5%) 59/68 (86.8%) 33/38 (86.8%) 92/106 (86.8%)
Blood and lymphatic system disorders
Anaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 13/68 (19.1%) 12/38 (31.6%) 25/106 (23.6%)
Cardiac disorders
Atrial fibrillation0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 3/68 (4.4%) 0/38 (0%) 3/106 (2.8%)
Bundle branch block0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Cardiac arrest0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Myocardial ischaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Palpitations0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Tachycardia0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Ear and labyrinth disorders
Ear pain0/2 (0%) 0/8 (0%) 0/8 (0%) 2/7 (28.6%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Tinnitus0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Endocrine disorders
Hyperthyroidism0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 8/68 (11.8%) 3/38 (7.9%) 11/106 (10.4%)
Hypothyroidism1/2 (50%) 1/8 (12.5%) 0/8 (0%) 1/7 (14.3%) 1/15 (6.7%) 3/25 (12%) 4/40 (10%) 5/68 (7.4%) 4/38 (10.5%) 9/106 (8.5%)
Eye disorders
Conjunctival haemorrhage1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Eye swelling0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Lacrimation increased0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
Punctate keratitis0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Vision blurred0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Gastrointestinal disorders
Abdominal discomfort0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Abdominal distension1/2 (50%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Abdominal pain1/2 (50%) 0/8 (0%) 2/8 (25%) 1/7 (14.3%) 1/15 (6.7%) 4/25 (16%) 5/40 (12.5%) 1/68 (1.5%) 2/38 (5.3%) 3/106 (2.8%)
Abdominal pain lower0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
Abdominal pain upper0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Constipation2/2 (100%) 4/8 (50%) 2/8 (25%) 3/7 (42.9%) 2/15 (13.3%) 11/25 (44%) 13/40 (32.5%) 2/68 (2.9%) 4/38 (10.5%) 6/106 (5.7%)
Diarrhoea1/2 (50%) 2/8 (25%) 3/8 (37.5%) 2/7 (28.6%) 4/15 (26.7%) 8/25 (32%) 12/40 (30%) 4/68 (5.9%) 5/38 (13.2%) 9/106 (8.5%)
Dry mouth1/2 (50%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 2/15 (13.3%) 2/25 (8%) 4/40 (10%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Duodenitis1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Dyspepsia1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Dysphagia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Enterocolitis0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Epigastric discomfort0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Faeces discoloured1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Flatulence0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Gastrointestinal pain0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Gingival pain1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Glossodynia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Haemorrhoids0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Impaired gastric emptying1/2 (50%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 1/15 (6.7%) 2/25 (8%) 3/40 (7.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Intestinal obstruction0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Nausea2/2 (100%) 1/8 (12.5%) 3/8 (37.5%) 0/7 (0%) 6/15 (40%) 6/25 (24%) 12/40 (30%) 5/68 (7.4%) 3/38 (7.9%) 8/106 (7.5%)
Oesophagitis1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Oral pain1/2 (50%) 0/8 (0%) 1/8 (12.5%) 1/7 (14.3%) 1/15 (6.7%) 3/25 (12%) 4/40 (10%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Pancreatic failure0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Paraesthesia oral0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Salivary duct inflammation0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Small intestinal obstruction0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Tongue ulceration0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Vomiting2/2 (100%) 2/8 (25%) 2/8 (25%) 1/7 (14.3%) 5/15 (33.3%) 7/25 (28%) 12/40 (30%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
General disorders
Asthenia1/2 (50%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 7/68 (10.3%) 6/38 (15.8%) 13/106 (12.3%)
Chest discomfort0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 2/68 (2.9%) 0/38 (0%) 2/106 (1.9%)
Chest pain0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 4/68 (5.9%) 0/38 (0%) 4/106 (3.8%)
Chills0/2 (0%) 0/8 (0%) 0/8 (0%) 2/7 (28.6%) 1/15 (6.7%) 2/25 (8%) 3/40 (7.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Fatigue1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 2/15 (13.3%) 1/25 (4%) 3/40 (7.5%) 8/68 (11.8%) 3/38 (7.9%) 11/106 (10.4%)
Generalised oedema2/2 (100%) 3/8 (37.5%) 4/8 (50%) 4/7 (57.1%) 5/15 (33.3%) 13/25 (52%) 18/40 (45%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Influenza like illness0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 1/68 (1.5%) 2/38 (5.3%) 3/106 (2.8%)
Injection site pain0/2 (0%) 0/8 (0%) 2/8 (25%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Localised oedema0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Malaise1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Mucosal inflammation2/2 (100%) 1/8 (12.5%) 0/8 (0%) 1/7 (14.3%) 1/15 (6.7%) 4/25 (16%) 5/40 (12.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Non-cardiac chest pain0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Oedema0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Oedema peripheral1/2 (50%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 3/68 (4.4%) 2/38 (5.3%) 5/106 (4.7%)
Pain0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Pyrexia0/2 (0%) 1/8 (12.5%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 8/68 (11.8%) 3/38 (7.9%) 11/106 (10.4%)
Systemic inflammatory response syndrome0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Hepatobiliary disorders
Hepatomegaly0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Hyperbilirubinaemia1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Jaundice0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Ocular icterus0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Portal hypertension1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Infections and infestations
Bronchitis0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Candida infection0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 3/15 (20%) 0/25 (0%) 3/40 (7.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Fungal skin infection0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Gastroenteritis0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Influenza0/2 (0%) 0/8 (0%) 1/8 (12.5%) 1/7 (14.3%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Nasopharyngitis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
Oral candidiasis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Oral herpes0/2 (0%) 2/8 (25%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Sepsis0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Sinusitis0/2 (0%) 0/8 (0%) 1/8 (12.5%) 1/7 (14.3%) 1/15 (6.7%) 2/25 (8%) 3/40 (7.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Tooth infection0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Upper respiratory tract infection0/2 (0%) 0/8 (0%) 2/8 (25%) 1/7 (14.3%) 3/15 (20%) 3/25 (12%) 6/40 (15%) 2/68 (2.9%) 2/38 (5.3%) 4/106 (3.8%)
Urinary tract infection2/2 (100%) 0/8 (0%) 1/8 (12.5%) 1/7 (14.3%) 2/15 (13.3%) 4/25 (16%) 6/40 (15%) 2/68 (2.9%) 5/38 (13.2%) 7/106 (6.6%)
Injury, poisoning and procedural complications
Cervical vertebral fracture0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Contusion0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Eye contusion0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Eye injury0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Fall0/2 (0%) 0/8 (0%) 2/8 (25%) 0/7 (0%) 1/15 (6.7%) 2/25 (8%) 3/40 (7.5%) 2/68 (2.9%) 2/38 (5.3%) 4/106 (3.8%)
Wound0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Wound dehiscence0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Investigations
Alanine aminotransferase increased0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 8/68 (11.8%) 2/38 (5.3%) 10/106 (9.4%)
Amylase increased0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 6/68 (8.8%) 4/38 (10.5%) 10/106 (9.4%)
Aspartate aminotransferase0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Aspartate aminotransferase increased1/2 (50%) 0/8 (0%) 1/8 (12.5%) 2/7 (28.6%) 1/15 (6.7%) 4/25 (16%) 5/40 (12.5%) 7/68 (10.3%) 2/38 (5.3%) 9/106 (8.5%)
Blood albumin decreased0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Blood alkaline phosphatase abnormal0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Blood alkaline phosphatase increased0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 5/68 (7.4%) 2/38 (5.3%) 7/106 (6.6%)
Blood bilirubin increased0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 5/68 (7.4%) 0/38 (0%) 5/106 (4.7%)
Blood creatinine increased2/2 (100%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 2/15 (13.3%) 4/25 (16%) 6/40 (15%) 3/68 (4.4%) 3/38 (7.9%) 6/106 (5.7%)
Blood lactate dehydrogenase increased0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 2/68 (2.9%) 0/38 (0%) 2/106 (1.9%)
Blood magnesium increased1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Blood phosphorus decreased1/2 (50%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Blood sodium decreased0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Blood thyroid stimulating hormone increased0/2 (0%) 0/8 (0%) 3/8 (37.5%) 0/7 (0%) 1/15 (6.7%) 3/25 (12%) 4/40 (10%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Body temperature increased0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 5/68 (7.4%) 1/38 (2.6%) 6/106 (5.7%)
Breath sounds abnormal0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Cardiac murmur0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Electrocardiogram QT prolonged1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Electrocardiogram ST segment depression0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Eosinophil count increased0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Haemoglobin decreased0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Lipase increased0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 5/68 (7.4%) 4/38 (10.5%) 9/106 (8.5%)
Neutrophil count decreased0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Platelet count decreased0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 3/68 (4.4%) 1/38 (2.6%) 4/106 (3.8%)
Weight decreased1/2 (50%) 0/8 (0%) 1/8 (12.5%) 1/7 (14.3%) 2/15 (13.3%) 3/25 (12%) 5/40 (12.5%) 4/68 (5.9%) 2/38 (5.3%) 6/106 (5.7%)
Weight increased0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
White blood cell count decreased0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Metabolism and nutrition disorders
Decreased appetite2/2 (100%) 3/8 (37.5%) 1/8 (12.5%) 0/7 (0%) 7/15 (46.7%) 6/25 (24%) 13/40 (32.5%) 9/68 (13.2%) 3/38 (7.9%) 12/106 (11.3%)
Dehydration1/2 (50%) 1/8 (12.5%) 1/8 (12.5%) 1/7 (14.3%) 3/15 (20%) 4/25 (16%) 7/40 (17.5%) 2/68 (2.9%) 1/38 (2.6%) 3/106 (2.8%)
Fluid overload0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Hyperammonaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Hypercalcaemia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 3/68 (4.4%) 3/38 (7.9%) 6/106 (5.7%)
Hyperglycaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Hyperkalaemia0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Hypermagnesaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 4/68 (5.9%) 0/38 (0%) 4/106 (3.8%)
Hyperuricaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 2/68 (2.9%) 0/38 (0%) 2/106 (1.9%)
Hypoalbuminaemia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 4/68 (5.9%) 1/38 (2.6%) 5/106 (4.7%)
Hypocalcaemia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 2/68 (2.9%) 0/38 (0%) 2/106 (1.9%)
Hypokalaemia1/2 (50%) 0/8 (0%) 2/8 (25%) 0/7 (0%) 3/15 (20%) 3/25 (12%) 6/40 (15%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Hypomagnesaemia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 2/15 (13.3%) 1/25 (4%) 3/40 (7.5%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
Hyponatraemia1/2 (50%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 2/68 (2.9%) 1/38 (2.6%) 3/106 (2.8%)
Hypophosphataemia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Hypovolaemia0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Increased appetite0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Musculoskeletal and connective tissue disorders
Arthralgia1/2 (50%) 1/8 (12.5%) 3/8 (37.5%) 1/7 (14.3%) 2/15 (13.3%) 6/25 (24%) 8/40 (20%) 4/68 (5.9%) 4/38 (10.5%) 8/106 (7.5%)
Back pain2/2 (100%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 4/15 (26.7%) 4/25 (16%) 8/40 (20%) 3/68 (4.4%) 6/38 (15.8%) 9/106 (8.5%)
Bone pain0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Flank pain0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
Foot deformity0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Groin pain0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Muscle spasms0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Myalgia0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Pain in extremity0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 2/68 (2.9%) 2/38 (5.3%) 4/106 (3.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Tumour pain0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Nervous system disorders
Balance disorder1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Burning sensation0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Disturbance in attention1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Dizziness1/2 (50%) 2/8 (25%) 1/8 (12.5%) 1/7 (14.3%) 0/15 (0%) 5/25 (20%) 5/40 (12.5%) 3/68 (4.4%) 1/38 (2.6%) 4/106 (3.8%)
Dysarthria0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Dysgeusia0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Headache1/2 (50%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 1/15 (6.7%) 3/25 (12%) 4/40 (10%) 3/68 (4.4%) 2/38 (5.3%) 5/106 (4.7%)
Memory impairment0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Neuralgia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Neuropathy peripheral1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Paraesthesia0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Peripheral sensory neuropathy0/2 (0%) 1/8 (12.5%) 2/8 (25%) 0/7 (0%) 0/15 (0%) 3/25 (12%) 3/40 (7.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Syncope0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Taste disorder1/2 (50%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Tremor1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Psychiatric disorders
Anxiety1/2 (50%) 2/8 (25%) 0/8 (0%) 0/7 (0%) 3/15 (20%) 3/25 (12%) 6/40 (15%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Confusional state0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Depression0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 2/68 (2.9%) 0/38 (0%) 2/106 (1.9%)
Insomnia1/2 (50%) 0/8 (0%) 1/8 (12.5%) 1/7 (14.3%) 1/15 (6.7%) 3/25 (12%) 4/40 (10%) 6/68 (8.8%) 0/38 (0%) 6/106 (5.7%)
Mental status changes0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Renal and urinary disorders
Acute kidney injury0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 2/38 (5.3%) 2/106 (1.9%)
Dysuria1/2 (50%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Haematuria0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 2/68 (2.9%) 2/38 (5.3%) 4/106 (3.8%)
Hypertonic bladder0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Pollakiuria1/2 (50%) 2/8 (25%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 3/25 (12%) 3/40 (7.5%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Proteinuria0/2 (0%) 0/8 (0%) 1/8 (12.5%) 1/7 (14.3%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 4/68 (5.9%) 2/38 (5.3%) 6/106 (5.7%)
Urinary tract pain0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Reproductive system and breast disorders
Breast pain1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Erectile dysfunction0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Respiratory, thoracic and mediastinal disorders
Cough1/2 (50%) 1/8 (12.5%) 3/8 (37.5%) 1/7 (14.3%) 4/15 (26.7%) 6/25 (24%) 10/40 (25%) 6/68 (8.8%) 2/38 (5.3%) 8/106 (7.5%)
Diaphragmalgia1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Dyspnoea1/2 (50%) 1/8 (12.5%) 2/8 (25%) 2/7 (28.6%) 5/15 (33.3%) 6/25 (24%) 11/40 (27.5%) 10/68 (14.7%) 0/38 (0%) 10/106 (9.4%)
Dyspnoea exertional0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 1/68 (1.5%) 2/38 (5.3%) 3/106 (2.8%)
Haemoptysis0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 4/68 (5.9%) 0/38 (0%) 4/106 (3.8%)
Hypoxia0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Nasal congestion0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Oropharyngeal pain0/2 (0%) 0/8 (0%) 1/8 (12.5%) 2/7 (28.6%) 1/15 (6.7%) 3/25 (12%) 4/40 (10%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Orthopnoea0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Pleural effusion0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 0/25 (0%) 0/40 (0%) 4/68 (5.9%) 1/38 (2.6%) 5/106 (4.7%)
Pleuritic pain0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Pneumonia aspiration0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Pneumonitis0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 4/68 (5.9%) 0/38 (0%) 4/106 (3.8%)
Pneumothorax0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Productive cough0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 7/68 (10.3%) 1/38 (2.6%) 8/106 (7.5%)
Rhinitis allergic0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Rhinorrhoea0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 0/38 (0%) 1/106 (0.9%)
Sinus congestion0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Sneezing0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Sputum discoloured0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Upper-airway cough syndrome1/2 (50%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Wheezing0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Skin and subcutaneous tissue disorders
Dermatitis bullous0/2 (0%) 1/8 (12.5%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Dry skin0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 1/68 (1.5%) 2/38 (5.3%) 3/106 (2.8%)
Hyperhidrosis0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 1/68 (1.5%) 1/38 (2.6%) 2/106 (1.9%)
Night sweats0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Pruritus1/2 (50%) 0/8 (0%) 1/8 (12.5%) 2/7 (28.6%) 0/15 (0%) 4/25 (16%) 4/40 (10%) 8/68 (11.8%) 4/38 (10.5%) 12/106 (11.3%)
Rash0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 5/68 (7.4%) 2/38 (5.3%) 7/106 (6.6%)
Rash maculo-papular0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Skin disorder0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Vascular disorders
Deep vein thrombosis0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Flushing0/2 (0%) 0/8 (0%) 1/8 (12.5%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Hot flush0/2 (0%) 0/8 (0%) 2/8 (25%) 0/7 (0%) 0/15 (0%) 2/25 (8%) 2/40 (5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Hypertension0/2 (0%) 0/8 (0%) 0/8 (0%) 1/7 (14.3%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 2/68 (2.9%) 1/38 (2.6%) 3/106 (2.8%)
Hypotension0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 1/25 (4%) 2/40 (5%) 2/68 (2.9%) 1/38 (2.6%) 3/106 (2.8%)
Lymphoedema0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 1/38 (2.6%) 1/106 (0.9%)
Peripheral embolism0/2 (0%) 0/8 (0%) 0/8 (0%) 0/7 (0%) 1/15 (6.7%) 0/25 (0%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)
Shock0/2 (0%) 1/8 (12.5%) 0/8 (0%) 0/7 (0%) 0/15 (0%) 1/25 (4%) 1/40 (2.5%) 0/68 (0%) 0/38 (0%) 0/106 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/TitlePfizer ClinicalTrials.gov Call Center
OrganizationPfizer Inc.
Phone1-800-718-1021
EmailClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02573259
Other Study ID Numbers:
  • B8011001
  • 2016-003314-27
First Posted:
Oct 9, 2015
Last Update Posted:
Dec 13, 2021
Last Verified:
Oct 1, 2021