The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Clinical Trial Details
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Other or Multiple Cancer Types
Integrin alpha-V/beta-8 Antagonist
PF-06940434 is an investigational compound. Its safety and efficacy have not been established.
A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06940434 IN PATIENTS WITH ADVANCED OR METASTATIC SOLID TUMORS
Phase 1
NCT04152018
Active Not-enrolling
Locations
United States, Australia, Korea, Republic of, Slovakia, Taiwan
Study design
Participant Group/Arm
EXPERIMENTAL: Dose Escalation
Single Agent Dose Escalation
Intervention/Treatment
DRUG: PF-06940434
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
Participant Group/Arm
EXPERIMENTAL: Dose Finding Anti-PD-1 Combination 1
Part 1B PF-06940434 plus anti-PD-1
Intervention/Treatment
DRUG: PF-06940434
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
DRUG: PF-06801591
PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.
Participant Group/Arm
EXPERIMENTAL: Dose Expansion Arm A
PF-06940434 with anti-PD-1 in SCCHN
Intervention/Treatment
DRUG: PF-06940434
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
DRUG: PF-06801591
PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.
Participant Group/Arm
EXPERIMENTAL: Dose Expansion Arm B
PF-06940434 with anti-PD-1 in RCC
Intervention/Treatment
DRUG: PF-06940434
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
DRUG: PF-06801591
PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.
Participant Group/Arm
EXPERIMENTAL: Dose Expansion, Arm C
PF-06940434 with anti-PD-1 (both Q3W)
Intervention/Treatment
DRUG: PF-06940434
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
DRUG: PF-06801591
PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.
Key eligibility criteria
Inclusion criteria
- 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 treatme
- Adequate bone marrow, kidney and liver function.
- Performance status of 0 or 1.
Exclusion criteria
- 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
Key dates
Study start date
- November 2019
Estimated primary completion date
- August 2024
Key endpoints
Primary Outcome Measures
Outcome Measure
Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding
Time Frame
Baseline up to 28 Days (Cycle 1)
Outcome Measure
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities
Time Frame
Baseline up to approximately 24 months
Outcome Measure
Number of Participants With Adverse Events (AEs) According to Severity
Time Frame
Baseline up to approximately 24 months
Outcome Measure
Number of Participants With Adverse Events (AEs) According to Seriousness
Time Frame
Baseline up to up to approximately 24 months
Outcome Measure
Number of Participants With Adverse Events (AEs) by Relationship
Time Frame
Baseline up to approximately 24 months
Outcome Measure
Progression-Free Survival (PFS) for Dose Expansion
Measure Description
The period from study entry until disease progression, death or date of last contact.
Time Frame
Baseline up to 24 Months
Outcome Measure
Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion
Time Frame
Baseline up to 24 months
Outcome Measure
Duration of Response (DR) for Dose Expansion
Time Frame
Baseline up to 24 Months
Secondary Outcome Measures:
Outcome Measure
PF-06940434 after multiple doses PK parameters (Cmax).
Measure Description
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).
Outcome Measure
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
Measure Description
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).
Outcome Measure
Systemic Clearance (CL)
Measure Description
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).
Outcome Measure
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).
Outcome Measure
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).
Outcome Measure
Incidence and titers of neutralizing antibodies (NAb) against PF-06940434.
Measure Description
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).
Outcome Measure
PK parameters of PF-06940434 and PF-06801591 (Cmax).
Measure Description
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)
Outcome Measure
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.
Measure Description
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)
Outcome Measure
Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.
Measure Description
Maximum observed plasma concentration of PF-06940434.
Time Frame
Cycle 4 Day 1 (each cycle is 28 days)
Outcome Measure
Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
Measure Description
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)
Outcome Measure
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)
Outcome Measure
Progression-Free Survival (PFS) for Dose Expansion
Measure Description
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)
Outcome Measure
Duration of Response (DR)
Time Frame
Baseline up to approximately 24 Months
Outcome Measure
Number of Participants With Objective Response for Dose Expansion portion
Time Frame
Baseline up to 24 months
Outcome Measure
Disease Control Rate (DCR)
Measure Description
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
Outcome Measure
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)
Outcome Measure
Plasma Decay Half-Life (t1/2)
Measure Description
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]
Outcome Measure
Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion
Measure Description
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].
Outcome Measure
Incidence and titers of neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion.
Measure Description
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].
Outcome Measure
Overall Survival
Measure Description
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
Number of participants
85
Collaborators and investigators
Sponsor: Pfizer
Collaborator: None