Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566
A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC CANCERS
3 other identifiers
interventional
174
4 countries
30
Brief Summary
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select 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 Apr 2015
Longer than P75 for phase_1
30 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
December 4, 2014
CompletedFirst Posted
Study publicly available on registry
December 11, 2014
CompletedStudy Start
First participant enrolled
April 23, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 12, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 12, 2020
CompletedResults Posted
Study results publicly available
April 21, 2022
CompletedApril 21, 2022
February 1, 2022
5.6 years
December 4, 2014
November 10, 2021
February 18, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Number of Participants With Dose Limiting Toxicities (DLTs) in Part A1
DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting \>7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
The first 2 cycles of treatment (Day 1 up to Day 28)
Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) and Serious Adverse Event(SAEs), Treatment-Related TEAEs and SAEs in Part A
Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. 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.
AEs: The informed consent date up to the last dosing date + 28 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period.
Number of Participants With Laboratory Test Abnormalities in Part A
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick \[protein, blood\], microscopy \[urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells\], miscellaneous \[urine casts and bacteria\]).
The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable)
Number of Participants With DLTs in Part B1
DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting \>7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
The First 2 Cycles of Treatment (Day 1 up to Day 28)
Number of Participants With All-causality TEAEs and SAEs, and Treatment-Related TEAEs and SAEs in Part B
Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. 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.
AEs: The informed consent date up to the last dosing date + 60 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period.
Number of Participants With Laboratory Test Abnormalities in Part B
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick \[protein, blood\], microscopy \[urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells\], miscellaneous \[urine casts and bacteria\]).
The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable)
Secondary Outcomes (45)
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 and Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST) in Part A
Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Progression-Free Survival (PFS) in Part A
Baseline up to 24 months post first dose
Kaplan-Meier Estimate of Median Time to Progression (TTP) in Part A
Baseline up to 24 months post first dose
Number of Participants Having Stable Disease (SD) in Part A
Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Duration of Response (DoR) in Part A
Baseline up to 24 months post first dose.
- +40 more secondary outcomes
Study Arms (2)
PF-04518600
EXPERIMENTALOX40 agonist
PF-04518600 plus PF-05082566
EXPERIMENTALOX40 (CD134) agonist plus 4-1BB (CD137) agonist
Interventions
Part A1 - PF-04518600 will be administered intravenously every 14 days in cohorts of 2 or more patients starting at a dose of 0.01 mg/kg. Increases in dose will continue until MTD is determined
Part B1 -In cohorts of 2 or more patients, PF-04518600 will be administered intravenously every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered intravenously 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined.
Eligibility Criteria
You may qualify if:
- Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
- Part A2 only: Patients with histological or cytological diagnosis of advanced/metastatic HCC who are treatment naïve and have declined standard of care, or have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is allowed.
- Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
- Part B2
- Arm 1 only:
- Ocular melanoma patients with advanced/metastatic disease, or
- Cutaneous/acral melanoma patients with advanced/metastatic disease who have received checkpoint inhibitor (anti PD L1, anti PD 1, or anti CTLA4) based treatment on which disease progressed. \[Note: Checkpoint inhibitor may have been part of a combination therapy, as long as the combination did not contain OX40 or 4 1BB agonist.\] Any questions on prior treatment may be discussed with the Sponsor.
- Arm 2 only:
- Histological or cytological diagnosis of NSCLC with advanced/metastatic disease. Patients must have previously received prior anti PD L1 or anti PD 1 mAb on which disease progressed. \[Note: Previous anti PD L1 or anti PD 1 mAb may have been part of a combination therapy, eg, in combination with chemotherapy, as long as the combination did not contain OX40 or 4 1BB agonist.\]
- Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function
You may not qualify if:
- Brain metastases requiring steroids
- Major surgery, Radiation therapy within 4 weeks of starting study treatment (except: palliative radiotherapy to a limited field is allowed after consultation with sponsor's medical monitor at any time during study participation, including during screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)
- Active and clinically significant bacterial, fungal, or viral infection
- History of active autoimmune disorders
- History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy
- Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)
- Prior anthracycline treatment and at risk of cardiac failure (New York Heart Association Class 2)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (30)
The Angeles Clinic And Research Institute, A Cedars-Sinai Affiliate
Los Angeles, California, 90025, United States
Keck Hospital of USC
Los Angeles, California, 90033, United States
LAC+USC Medical Center
Los Angeles, California, 90033, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Ronald Regan Medical Center
Los Angeles, California, 90095, United States
UCLA Hematology & Oncology Clinic
Los Angeles, California, 90095, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663, United States
Medical Imaging Center of Southern California, Inc.
Santa Monica, California, 90403, United States
Santa Monica UCLA Hematology & Oncology Clinic
Santa Monica, California, 90404, United States
UConn Health, Pharmacy
Farmington, Connecticut, 06030-2205, United States
UConn Health, Neag Comprehensive Cancer Center
Farmington, Connecticut, 06030, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612, United States
Massachusetts General Hospital (MGH)
Boston, Massachusetts, 02114, United States
Brigham & Women's Hospital (BWH)
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center (BIDMC)
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute (DFCI)
Boston, Massachusetts, 02215, United States
Massachusetts General/Chelsea HealthCare Center
Chelsea, Massachusetts, 02150, United States
Mass General/North Shore Center for Outpatient Care
Danvers, Massachusetts, 01923, United States
Mass General West
Waltham, Massachusetts, 02451, United States
Columbia University Medical Center - Herbert Irving Pavilion
New York, New York, 10032, United States
Methodist Hospital-Pathology
Houston, Texas, 77030, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Groupe hospitalier Pitie Salpetriere
Paris, 75013, France
Institut Gustave Roussy
Villejuif, 94805, France
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577, Japan
The Netherlands Cancer Institute
Amsterdam, 1066 CX, Netherlands
Slotervaart Hospital/Antoni van Leeuwenhoek
Amsterdam, 1066 EC, Netherlands
Erasmus MC
Rotterdam, 3015 GD, Netherlands
Related Publications (2)
Hamid O, Chiappori AA, Thompson JA, Doi T, Hu-Lieskovan S, Eskens FALM, Ros W, Diab A, Spano JP, Rizvi NA, Wasser JS, Angevin E, Ott PA, Forgie A, Yang W, Guo C, Chou J, El-Khoueiry AB. First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors. J Immunother Cancer. 2022 Oct;10(10):e005471. doi: 10.1136/jitc-2022-005471.
PMID: 36302562DERIVEDDiab A, Hamid O, Thompson JA, Ros W, Eskens FALM, Doi T, Hu-Lieskovan S, Klempner SJ, Ganguly B, Fleener C, Wang X, Joh T, Liao K, Salek-Ardakani S, Taylor CT, Chou J, El-Khoueiry AB. A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients with Locally Advanced or Metastatic Cancers. Clin Cancer Res. 2022 Jan 1;28(1):71-83. doi: 10.1158/1078-0432.CCR-21-0845. Epub 2021 Oct 6.
PMID: 34615725DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
A decision was made by the sponsor to terminate further enrollment to the study on 03 Oct 2018 due to business reasons. The decision to terminate study enrollment was not based on any safety or regulatory concerns.
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
- Masking Details
- Open-label
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 4, 2014
First Posted
December 11, 2014
Study Start
April 23, 2015
Primary Completion
November 12, 2020
Study Completion
November 12, 2020
Last Updated
April 21, 2022
Results First Posted
April 21, 2022
Record last verified: 2022-02
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.