Open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06940434 (Integrin alpha-V/beta-8 Antagonist) in patients with SCCHN (Squamous Cell Carcinoma of the Head and Neck), renal cell carcinoma (RCC - clear cell and papillary), ovarian, gastric, esophageal, esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct, endometrial, melanoma and urothelial tumors. This study contains two parts, single agent dose escalation (Part 1A), dose finding of PF 06940434 in combination with anti-PD-1 (Part 1B) and dose expansion (Part 2). Part 2 Dose Combination Expansion will enroll participants into 3 cohorts at doses determined from Part 1B in order to further evaluate the safety of PF-06940434 in combination with anti-PD-1.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
PF-06940434 is given intravenously (IV) every 2 or 4 weeks in a 28 day cycle or every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated
PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.
HonorHealth Research Institute
Scottsdale, Arizona, United States
HonorHealth Scottsdale Shea Medical Center
Scottsdale, Arizona, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
UCLA Hematology Oncology
Los Angeles, California, United States
UCLA Hematology/Oncology
Santa Monica, California, United States
Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding
Time frame: Baseline up to 28 Days (Cycle 1)
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities
Time frame: Baseline up to approximately 24 months
Number of Participants With Adverse Events (AEs) According to Severity
Time frame: Baseline up to approximately 24 months
Number of Participants With Adverse Events (AEs) According to Seriousness
Time frame: Baseline up to up to approximately 24 months
Number of Participants With Adverse Events (AEs) by Relationship
Time frame: Baseline up to approximately 24 months
Progression-Free Survival (PFS) for Dose Expansion
The period from study entry until disease progression, death or date of last contact.
Time frame: Baseline up to 24 Months
Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion
Time frame: Baseline up to 24 months
Duration of Response (DR) for Dose Expansion
Time frame: Baseline up to 24 Months
PF-06940434 after multiple doses PK parameters (Cmax).
Maximum observed plasma concentration of PF-06940434.
Time frame: Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
Time zero extrapolated to the last quantifiable time point prior to the next dose.
Time frame: Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).
Systemic Clearance (CL)
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).
Volume of Distribution (Vd)
Time frame: Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).
Incidence and titers of anti-drug antibodies (ADA) against PF-06940434.
Time frame: Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).
Incidence and titers of neutralizing antibodies (NAb) against PF-06940434.
Titers of neutralizing antibodies (NAb) against PF-06940434.
Time frame: Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).
PK parameters of PF-06940434 and PF-06801591 (Cmax).
Maximum observed plasma concentration after multiple doses of PF-06940434 and PD-1 (PF-06801591).
Time frame: Pre-dose on Cycle 1 Day 1 and on day 15 of Cycle 1; Day 1 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.
Time frame: Pre-dose on Cycle 1 Day 1 and on day 15 of Cycle 1; Day 1 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.
Maximum observed plasma concentration of PF-06940434.
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
Time zero extrapolated to the last quantifiable time point prior to the next dose.
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Number of participants with increased T-cells after PF-06940434 treatment.
Time frame: Pre-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2 and 3 (each cycle is 28 days)
Progression-Free Survival (PFS) for Dose Expansion
The period from study entry until disease progression, death or date of last contact.
Time frame: Baseline to measured progression (up to approximately 24 months)
Duration of Response (DR)
Time frame: Baseline up to approximately 24 Months
Number of Participants With Objective Response for Dose Expansion portion
Time frame: Baseline up to 24 months
Disease Control Rate (DCR)
DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1.
Time frame: Every 8 weeks from the time of enrollment up to 2 years
Trough concentrations of PF-06940434 and PF-06801591 in Dose Expansion
Time frame: Day 1 of Cycle 1 though 4, Day 1 of every 2 Cycles starting from Cycle 5 up to 24 months (each cycle is 28 days). For Part 2 Cohort 3, Day 1 of Every Cycle (each cycle is 21 days)
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days]
Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion
Incidence and titers of anti-drug antibodies (ADA) against PF-06801591.
Time frame: Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days].
Incidence and titers of neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion.
Incidence and titers of neutralizing antibodies (NAb) against PF-06801591.
Time frame: Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days].
Overall Survival
The period from study entry until death or date of last contact (24 months)
Time frame: From baseline to up to 2 years after last dose of study drug
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Greenebaum Comprehensive Cancer Center
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Siteman Cancer Center - St. Peters
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