PF-07265028 As Single Agent And In Combination With Sasanlimab in Advanced or Metastatic Solid Tumors

A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-07265028 AS A SINGLE AGENT AND IN COMBINATION WITH SASANLIMAB EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07265028 IN PARTICIPANTS WITH ADVANCED OR METASTATIC SOLID TUMORS

The purpose of this study is to assess the safety and effects of PF-07265028 as monotherapy and in combination with sasanlimab.

The study aims to identify the maximum tolerated dose (MTD) of PF-07265028 as monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development.

The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.

It is expected that most participants will take part in this study for up to 1 year with six on-site visits in the first month and then at least twice every subsequent month while they are on treatment.

Study Overview

• Status: Terminated
• Conditions: Gastric Cancer; Non Small Cell Lung Cancer; Advanced Solid Tumors; Gastroesophageal Junction Cancer; Urothelial Cancer; Head and Neck Squamous Cell Carcinomas
• Intervention / Treatment: Drug: PF-07265028; Biological: Sasanlimab

Detailed Description

The purpose of this first-in-human study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of increasing doses of PF-07265028 as monotherapy and in combination with sasanlimab; identify the maximum tolerated dose (MTD) of PF-07265028 monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development. The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Tokyo
    • Koto, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of JFCR
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
    • Scottsdale, Arizona, United States, 85260
      • HonorHealth Scottsdale Shea Medical Center
  • Florida
    • Margate, Florida, United States, 33063
      • D&H Cancer Research Center LLC
    • Margate, Florida, United States, 33063
      • Napa Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research - Medical City Hospital
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics (START)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Across all cohorts:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
2. Adequate hematological, kidney and liver function
3. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
4. Resolved acute effects of any prior therapy
5. All participants must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue:

Part 1: If archival sample is older than 6 months, the participant must consent to undergo a fresh biopsy during the screening.

Part 2 Fresh tumor biopsy during screening is required unless there is archival tissues less than 3 months old and subsequent to the last systemic anti-cancer therapy.

Part 1A Monotherapy:

Histologically or cytologically confirmed advanced or metastatic solid tumors which have progressed following systemic anticancer therapies, or are resistant to standard therapy or for which no standard therapy is available, or for whom standard therapy is not tolerated.

Part 1B Combination Therapy:

Histologically or cytologically confirmed advanced or metastatic solid tumor which have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor.

Part 2 Dose Expansion:

Histologically or cytologically confirmed advanced or metastatic malignancies, including gastric/Gastroesophageal junction cancer, Head and neck squamous cell carcinoma, or urothelial cancer (non-small cell lung cancer and other solid tumors may be included) who have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor

Key Exclusion Criteria:

1. Participants with any other active malignancy within 3 years prior to enrollment
2. Participants with active autoimmune conditions or history of autoimmune diseases that may relapse
3. History of interstitial lung disease, pneumonitis (non-infectious) or uncontrolled lung diseases
4. History of prior immune-related adverse events (irAEs) Grade ≥3
5. Central nervous system metastases
6. Significant cardiac or pulmonary conditions or events within previous 6 months
7. Active, uncontrolled bacterial, fungal, or viral infection
8. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PF-07265028
9. Prior administration of HPK1 inhibitor

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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A Dose Escalation Monotherapy; Participants will receive PF-07265028 at escalating dose levels.	Drug: PF-07265028; PF-07265028 will be administered orally
Experimental: Part 1B Dose Escalation Combination; Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose	Drug: PF-07265028; PF-07265028 will be administered orally; Biological: Sasanlimab; Administered subcutaneously; Other Names: PF-06801591
Experimental: Part 2A Dose Expansion Combination (SCCHN); Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B	Drug: PF-07265028; PF-07265028 will be administered orally; Biological: Sasanlimab; Administered subcutaneously; Other Names: PF-06801591
Experimental: Part 2A Dose Expansion Combination (UC); Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B	Drug: PF-07265028; PF-07265028 will be administered orally; Biological: Sasanlimab; Administered subcutaneously; Other Names: PF-06801591
Experimental: Part 2A Dose Expansion Combination (Gastric/GEJ); Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B	Drug: PF-07265028; PF-07265028 will be administered orally; Biological: Sasanlimab; Administered subcutaneously; Other Names: PF-06801591
Experimental: Part 2A Dose Expansion Combination (NSCLC); Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B	Drug: PF-07265028; PF-07265028 will be administered orally; Biological: Sasanlimab; Administered subcutaneously; Other Names: PF-06801591
Experimental: Part 2A Dose Expansion Combination (selected tumor types); Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B	Drug: PF-07265028; PF-07265028 will be administered orally; Biological: Sasanlimab; Administered subcutaneously; Other Names: PF-06801591
Experimental: Part 2B Dose Expansion Monotherapy (selected tumor types); Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A.	Drug: PF-07265028; PF-07265028 will be administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1)	DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose	Cycle 1 (28 days)
Number of participants with adverse events (AEs)	AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), timing, seriousness, and relationship to study therapy.	Baseline through up to 2 years
Number of participants with clinically significant laboratory abnormalities	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.	Baseline through up to 2 years
Objective response rate (ORR) in Dose Expansion (Part 2)	Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Baseline through up to 2 years or until disease progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax.	Maximum observed plasma concentration of PF-07265028 (Cmax) and Maximum observed steady state plasma concentration (Cmax, ss)	Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax.	Time to maximal observed plasma concentration of PF-07265028 (Tmax) and Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).	Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC	Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 and area under the curve within one dose interval at steady state (AUCtau,ss)	Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax.	Maximum observed plasma concentration of PF-07265028 (Cmax) under fasted and fed conditions in the subset of participants	Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax	Time to maximal observed plasma concentration of PF-07265028 (Tmax) under fasted and fed conditions in the subset of participants	Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
The effect of food on the pharmacokinetic profile of PF-07265028 through AUC	Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 under fasted and fed conditions in the subset of participants	Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin	Minimum plasma concentration (Cmin) will be calculated through the measured pre-dose plasma concentration	Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days)
The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb	Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against sasanlimab	Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days)
The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation	Levels of intratumor T cells and PD-L1 expression in pre- and post-treatment tumor biopsies	Baseline through up to 2 years
ORR in Dose Escalation (Part 1)	Tumor response assessment based on RECIST 1.1	From baseline through disease progression or study completion (approximately 2 years)
Time to event endpoints (DOR) in Dose Expansion (Part 2)	Duration of response (DOR) as assessed using RECIST 1.1.	From baseline through disease progression or study completion (approximately 2 years)
Time to event endpoints (PFS) in Dose Expansion (Part 2)	Progression free survival (PFS) as assessed using RECIST 1.1.	From baseline through disease progression or study completion (approximately 2 years)
Time to event endpoints (OS) in Dose Expansion (Part 2)	Overall survival (OS) assessed proportion of patients alive	From baseline through disease progression or study completion (approximately 2 years)

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): February 24, 2022
• Primary Completion (Actual): October 16, 2023
• Study Completion (Actual): October 16, 2023

Study Registration Dates

• First Submitted: January 6, 2022
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Estimated): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; NSCLC; Gastric cancer; Lung cancer; Gastroesophageal junction cancer; advanced solid tumor; metastatic solid tumor; Non small cell lung cancer; Urothelial Cancer; SCCHN; first in human; Head and neck squamous cell carcinomas; Hematopoietic progenitor kinase 1 inhibitor; HPK1 inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Stomach Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: C4731001

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