Study of PF-06940434 in Patients With Advanced or Metastatic Solid Tumors.
- Conditions
- Squamous Cell Carcinoma of the Head and NeckMelanoma CancerGastric CancerPancreatic CancerEsophageal CancerBile Duct CancerEndometrial CancerRenal Cell CarcinomaLung Squamous Cell CarcinomaOvarian Cancer
- Interventions
- Registration Number
- NCT04152018
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 85
- Histological or cytological diagnosis of SCCHN, RCC (clear cell and papillary cell), ovarian, gastric, esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct, endometrial, melanoma, or urothelial cancer.
Part 2:
-
Arm A SCCHN:
- Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx.
- PDL-1 expression positive and CPS ≥1. No prior systemic therapy administered in the recurrent or metastatic setting (except for systemic therapy given as part of a multimodal treatment for locally advanced disease).
-
Arm B RCC (clear cell):
- 1 or 2 prior lines of therapy including PD-L1/PD-1 immunotherapy in combination or sequentially with antiangiogenic directed treatment
-
Adequate bone marrow, kidney and liver function.
-
Performance status of 0 or 1.
- Participant disease status is suitable for local therapy administered with curative intent.
- Hypertension that cannot be controlled by medications.
- Active or prior autoimmune disease
- Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) Hepatitis B, Hepatitis C, and known Human Immunodeficiency Virus infection or Acquired Immunodeficiency Syndrome-related illness
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion, Arm C PF-06801591 PF-06940434 with anti-PD-1 (both Q3W) Dose Escalation PF-06940434 Single Agent Dose Escalation Dose Expansion Arm B PF-06940434 PF-06940434 with anti-PD-1 in RCC Dose Finding Anti-PD-1 Combination 1 PF-06940434 Part 1B PF-06940434 plus anti-PD-1 Dose Expansion Arm A PF-06940434 PF-06940434 with anti-PD-1 in SCCHN Dose Expansion, Arm C PF-06940434 PF-06940434 with anti-PD-1 (both Q3W) Dose Finding Anti-PD-1 Combination 1 PF-06801591 Part 1B PF-06940434 plus anti-PD-1 Dose Expansion Arm A PF-06801591 PF-06940434 with anti-PD-1 in SCCHN Dose Expansion Arm B PF-06801591 PF-06940434 with anti-PD-1 in RCC
- Primary Outcome Measures
Name Time Method Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities Baseline up to approximately 24 months Duration of Response (DR) for Dose Expansion Baseline up to 24 Months Number of Participants With Adverse Events (AEs) According to Seriousness Baseline up to up to approximately 24 months Progression-Free Survival (PFS) for Dose Expansion Baseline up to 24 Months The period from study entry until disease progression, death or date of last contact.
Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion Baseline up to 24 months Number of Participants With Adverse Events (AEs) According to Severity Baseline up to approximately 24 months Number of Participants With Adverse Events (AEs) by Relationship Baseline up to approximately 24 months Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding Baseline up to 28 Days (Cycle 1)
- Secondary Outcome Measures
Name Time Method Volume of Distribution (Vd) 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 neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion. 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.
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434. Cycle 4 Day 1 (each cycle is 28 days) Time zero extrapolated to the last quantifiable time point prior to the next dose.
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591. 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.
Trough concentrations of PF-06940434 and PF-06801591 in Dose Expansion 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) PF-06940434 after multiple doses PK parameters (Cmax). 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). Maximum observed plasma concentration of PF-06940434.
Incidence and titers of anti-drug antibodies (ADA) against PF-06940434. 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). 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) Maximum observed plasma concentration after multiple doses of PF-06940434 and PD-1 (PF-06801591).
Systemic Clearance (CL) 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). CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Number of participants with increased T-cells after PF-06940434 treatment. 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 Baseline to measured progression (up to approximately 24 months) The period from study entry until disease progression, death or date of last contact.
Duration of Response (DR) Baseline up to approximately 24 Months Number of Participants With Objective Response for Dose Expansion portion Baseline up to 24 months Disease Control Rate (DCR) Every 8 weeks from the time of enrollment up to 2 years 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.
Incidence and titers of neutralizing antibodies (NAb) against PF-06940434. 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). Titers of neutralizing antibodies (NAb) against PF-06940434.
Plasma Decay Half-Life (t1/2) 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] Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion 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 anti-drug antibodies (ADA) against PF-06801591.
Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591. Cycle 4 Day 1 (each cycle is 28 days) Maximum observed plasma concentration of PF-06940434.
Overall Survival From baseline to up to 2 years after last dose of study drug The period from study entry until death or date of last contact (24 months)
Trial Locations
- Locations (31)
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
Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Siteman Cancer Center - North County
🇺🇸Florissant, Missouri, United States
Duke Univ. Medical Center/Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Investigational Chemotherapy Service
🇺🇸Durham, North Carolina, United States
Nemocnica Poprad a.s.
🇸🇰Poprad, Slovakia
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - St. Peters
🇺🇸Saint Peters, Missouri, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Southern Medical Day Care Centre
🇦🇺Wollongong, New South Wales, Australia
Asan Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Onkologicky ustav sv. Alzbety, s.r.o.
🇸🇰Bratislava, Slovakia
Univerzitna nemocnica Bratislava
🇸🇰Bratislava, Slovakia
Narodny ustav srdcovych a cievnych chorob, a.s.
🇸🇰Bratislava, Slovakia
MR Poprad s.r.o.
🇸🇰Komárno, Slovakia
KARDIO, s.r.o.
🇸🇰Poprad, Slovakia
POKO Poprad, s.r.o., Ambulancia klinickej onkologie
🇸🇰Poprad, Slovakia
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan