Study of PF-06940434 in Patients With Advanced or Metastatic Solid Tumors.

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

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 Overview

• Status: Terminated
• Conditions: Renal Cell Carcinoma; Gastric Cancer; Pancreatic Cancer; Esophageal Cancer; Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck; Bile Duct Cancer; Endometrial Cancer; Urothelial Cancer; Lung Squamous Cell Carcinoma; Melanoma Cancer
• Intervention / Treatment: Drug: PF-06940434; Drug: PF-06801591

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul-teukbyeolsi [seoul]
    • Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of, 05505
      • Asan Medical Center
• Slovakia
  • Bratislava, Slovakia, 833 48
    • Narodny ustav srdcovych a cievnych chorob, a.s.
  • Bratislava, Slovakia, 812 50
    • Onkologicky ustav sv. Alzbety, s.r.o.
  • Bratislava, Slovakia, 82101
    • Univerzitna nemocnica Bratislava
  • Komárno, Slovakia, 945 01
    • MR Poprad s.r.o.
  • Poprad, Slovakia, 058 01
    • POKO Poprad, s.r.o., Ambulancia klinickej onkologie
  • Poprad, Slovakia, 058 01
    • KARDIO, s.r.o.
  • Poprad, Slovakia, 058 45
    • Nemocnica Poprad a.s.
• Taiwan
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
    • Scottsdale, Arizona, United States, 85260
      • HonorHealth Scottsdale Shea Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Hematology Oncology
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Comprehensive Cancer Center
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center - West County
    • Florissant, Missouri, United States, 63031
      • Siteman Cancer Center - North County
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center - South County
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Siteman Cancer Center
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center - St. Peters
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Univ. Medical Center/Duke Cancer Center
    • Durham, North Carolina, United States, 27710
      • Investigational Chemotherapy Service
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 treatment
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Single Agent Dose Escalation	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
Experimental: Dose Finding Anti-PD-1 Combination 1; Part 1B PF-06940434 plus anti-PD-1	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.; Other Names: Anti-PD-1
Experimental: Dose Expansion Arm A; PF-06940434 with anti-PD-1 in SCCHN	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.; Other Names: Anti-PD-1
Experimental: Dose Expansion Arm B; PF-06940434 with anti-PD-1 in RCC	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.; Other Names: Anti-PD-1
Experimental: Dose Expansion, Arm C; PF-06940434 with anti-PD-1 (both Q3W)	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.; Other Names: Anti-PD-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities		Baseline up to approximately 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) According to Seriousness		Baseline up to 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)
Progression-Free Survival (PFS) for Dose Expansion	The period from study entry until disease progression, death or date of last contact.	Baseline up to 24 Months
Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion		Baseline up to 24 months
Duration of Response (DR) for Dose Expansion		Baseline up to 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters of PF-06940434 and PF-06801591 (Cmax).	Maximum observed plasma concentration after multiple doses of PF-06940434 and PD-1 (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.	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)
Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.	Maximum observed plasma concentration of PF-06940434.	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.	Cycle 4 Day 1 (each cycle is 28 days)
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	The period from study entry until disease progression, death or date of last contact.	Baseline to measured progression (up to approximately 24 months)
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)	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.	Every 8 weeks from the time of enrollment up to 2 years
Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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]
PF-06940434 after multiple doses PK parameters (Cmax).	Maximum observed plasma concentration of PF-06940434.	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.	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.	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)		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.		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.	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).
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)
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.	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.	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)	From baseline to up to 2 years after last dose of study drug

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): December 10, 2024
• Study Completion (Actual): December 10, 2024

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 2, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Head and Neck Neoplasms; Biliary Tract Diseases; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Bile Duct Diseases; Biliary Tract Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Bile Duct Neoplasms
• Other Study ID Numbers: C3891001; 2020-004009-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No