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
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.
2 other identifiers
interventional
147
7 countries
67
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2016
Longer than P75 for phase_1
67 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 6, 2015
CompletedFirst Posted
Study publicly available on registry
October 9, 2015
CompletedStudy Start
First participant enrolled
February 10, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 19, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 19, 2020
CompletedResults Posted
Study results publicly available
December 13, 2021
CompletedDecember 13, 2021
October 1, 2021
4.8 years
October 6, 2015
September 13, 2021
October 29, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Percentage of Participants With Dose-Limiting Toxicities (DLT) - Part 1
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.
Cycle 1 in Part 1 (21 days for IV administration of PF-06801591; 28 days for SC administration of PF-06801591)
Number of Participants With All-Causality Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
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.
Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
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.
Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
Number of Participants With Laboratory Test Abnormalities - Part 1 and Part 2
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.
Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
Objective Response Rate (ORR) Based on RECIST Version 1.1 - Part 2
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.
Baseline up to end of treatment in Part 2 (maximum of 851 days)
Objective Response Rate (ORR) Based on Immune Related RECIST (irRECIST) - Part 2
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.
Baseline up to end of treatment in Part 2 (maximum of 851 days)
Secondary Outcomes (19)
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
AUClast of PF-06801591 in Part 1.
Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1 in Part 1
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
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
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
- +14 more secondary outcomes
Study Arms (5)
Arm 1 PF-06801591
EXPERIMENTAL0.5 mg/kg IV every 21 days (Part 1)
Arm 2 PF-06801591
EXPERIMENTAL1.0 mg/kg IV every 21 days (Part 1)
Arm 3 PF-06801591
EXPERIMENTAL3.0 mg/kg IV every 21 days (Part 1)
Arm 4 PF-06801591
EXPERIMENTAL10 mg/kg IV every 21 days (Part 1)
Arm 5 PF-06801591
EXPERIMENTAL300 mg SC every 28 days (Part 1 and 2)
Interventions
IV every 21 days (Part 1)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (67)
Clinical Research Unit
Los Angeles, California, 90024, United States
Ronald Reagan Medical Center, Department of Radiological Sciences
Los Angeles, California, 90095, United States
Ronald Reagan UCLA Medical Center, Drug Information Center
Los Angeles, California, 90095, United States
UCLA Hematology & Oncology Clinic
Los Angeles, California, 90095, United States
Santa Monica UCLA Hematology & Oncology Clinic
Santa Monica, California, 90404, United States
Norton Cancer Institute, Multidisciplinary Clinic
Louisville, Kentucky, 40202, United States
Norton Cancer Institute, Norton Healthcare Pavilion
Louisville, Kentucky, 40202, United States
Norton Hospital
Louisville, Kentucky, 40202, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
University of Rochester
Rochester, New York, 14642, United States
UNC Hospitals, The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7600, United States
Tennessee Oncology, PLLC
Dickson, Tennessee, 37055, United States
Tennessee Oncology, PLLC
Franklin, Tennessee, 37067, United States
Tennessee Oncology, PLLC
Gallatin, Tennessee, 37066, United States
Tennessee Oncology, PLLC
Hermitage, Tennessee, 37076, United States
Tennessee Oncology, PLLC
Lebanon, Tennessee, 37090, United States
Tennessee Oncology, PLLC
Murfreesboro, Tennessee, 37129, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
The Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37205, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37207, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37211, United States
Tennessee Oncology, PLLC
Shelbyville, Tennessee, 37160, United States
Tennessee Oncology, PLLC
Smyrna, Tennessee, 37167, United States
MHAT Uni Hospital OOD
Panagyurishte, Pazardzhik, 4500, Bulgaria
Complex Oncology Center - Plovdiv EOOD
Plovdiv, 4000, Bulgaria
"MHAT for Women Health - Nadezhda" OOD
Sofia, 1330, Bulgaria
SHATOD "Dr. Marko Antonov Markov - Varna" EOOD
Varna, 9002, Bulgaria
Hospital Sultan Ismail
Johor Bahru, Johor, 81100, Malaysia
University Malaya Medical Centre
Lembah Pantai, Kuala Lumpur, 59100, Malaysia
Hospital Tengku Ampuan Afzan
Kuantan, Pahang, 25100, Malaysia
Clinical Research Centre(Crc), Hospital Umum Sarawak
Kuching, Sarawak, 93586, Malaysia
Szpitale Pomorskie Sp. z.o.o., Oddzial Onkologii i Radioterapii
Gdynia, 81-519, Poland
Regionalny Szpital Specjalistyczny im. dr. Wl. Bieganskiego w Grudziadzu
Grudziądz, 86-300, Poland
Centrum Badan Klinicznych JCI Life Science Park
Krakow, 30-348, Poland
Mazowiecki Szpital Specjalistyczny im. Dr. Jozefa Psarskiego w Ostrolece, Osrodek Onkologiczny
Ostrołęka, 07-410, Poland
Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina
Otwock, 05-400, Poland
Centrum Onkologii-Instytut im.Marii Sklodowskiej-Curie
Warsaw, 02-781, Poland
Sbhi "Lrcod"
Vsevolozhsky District, Leningradskaya Oblast', 188663, Russia
SBHI ¨Saint-Petersburg clinical scientific practical center of specialized types of
Pesochny Village, Sankt-Peterburg, 197758, Russia
SBHI "ChRCCO and NM"
Chelyabinsk, 454087, Russia
MROI n.a. P.A. Gertsen, filiation of FSBI "NMRC of radiology" MoH Russia
Moscow, 125284, Russia
BHI of Omsk Region "Clinical Oncology Dispensary"
Omsk, 644013, Russia
Joint Stock Company Current medical technologies
Saint Petersburg, 190013, Russia
Joint-Stock Company Current medical technologies
Saint Petersburg, 190121, Russia
Non-governmental Healthcare Institution ¨Railway Clinical Hospital of JSC ¨Russian Railways¨
Saint Petersburg, 195271, Russia
SPb SBHI "City Clinical Oncology Dispensary"
Saint Petersburg, 197022, Russia
SPb SBHI "City Clinical Oncology Dispensary"
Saint Petersburg, 198255, Russia
SBHI YaR ¨Regional clinical oncology hospital¨
Yaroslavl, 150054, Russia
National Cancer Center
Goyang-si, Gyeonggi-do, 10408, South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620, South Korea
The Catholic University of Korea, St. Vincent's Hospital
Suwon, Gyeonggi-do, 16247, South Korea
Gachon University Gil Medical Center
Incheon, 21565, South Korea
Division of Medical Oncology, Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Severance Hospital Yonsei University Health System
Seoul, 03722, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Ulsan University Hospital
Ulsan, 44033, South Korea
Communal Non-profit Institution "City Clinical Hospital #4" of Dnipro City Council, Department of
Dnipro, 49102, Ukraine
Communal non-Commercial Enterprise "Prykarpatski Clinical Oncological Center of Ivano-
Ivano-Frankivsk, 79018, Ukraine
Grigoriev Radiological Institute of the National Academy of Medical Sciences of Ukraine,
Kharkiv, 61024, Ukraine
Communal Non-profit Institution of Kharkiv Regional Council "Regional Clinical Specialized Health
Kharkiv, 61166, Ukraine
"Specialized Clinic "Prognosis Optima" LLC
Kyiv, 03126, Ukraine
Communal noncommercial enterprise Sumy regional Rada Sumy regional clinical oncologic dispensary,
Sumy, 40030, Ukraine
Communal Non-profit Institution "Central City Clinical Hospital" of Uzhhorod City Council,
Uzhhorod, 88000, Ukraine
Vinnytsia Regional Clinical Oncological Hospital
Vinnytsia, 21029, Ukraine
Communal Institution ¨Zaporizhzhya Regional Clinical Oncological Dispensary¨
Zaporizhzhya, 69040, Ukraine
Related Publications (3)
Sako C, Duan C, Maresca K, Kent S, Schmidt TG, Aerts HJWL, Parikh RB, Simon GR, Jordan P. Real-World and Clinical Trial Validation of a Deep Learning Radiomic Biomarker for PD-(L)1 Immune Checkpoint Inhibitor Response in Advanced Non-Small Cell Lung Cancer. JCO Clin Cancer Inform. 2024 Dec;8:e2400133. doi: 10.1200/CCI.24.00133. Epub 2024 Dec 13.
PMID: 39671539DERIVEDHu-Lieskovan S, Braiteh F, Grilley-Olson JE, Wang X, Forgie A, Bonato V, Jacobs IA, Chou J, Johnson ML. Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration. Target Oncol. 2021 Nov;16(6):773-787. doi: 10.1007/s11523-021-00833-2. Epub 2021 Oct 25.
PMID: 34694529DERIVEDJohnson ML, Braiteh F, Grilley-Olson JE, Chou J, Davda J, Forgie A, Li R, Jacobs I, Kazazi F, Hu-Lieskovan S. Assessment of Subcutaneous vs Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2019 Jul 1;5(7):999-1007. doi: 10.1001/jamaoncol.2019.0836.
PMID: 31145415DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 6, 2015
First Posted
October 9, 2015
Study Start
February 10, 2016
Primary Completion
November 19, 2020
Study Completion
November 19, 2020
Last Updated
December 13, 2021
Results First Posted
December 13, 2021
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will not share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.