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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05233436

Collaborator

(none)

240

Enrollment

Locations

Arms

58.4

Anticipated Duration (Months)

34.3

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and dose expansion study intended to evaluate the safety, pharmacokinetic, pharmacodynamic and potential clinical benefit of PF-07265028 as a single agent and in combination with sasanlimab, Anti-programmed cell death-1 (PD-1) monoclonal antibody, in participants with advanced or metastatic solid tumors for whom no standard therapy is available.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors Gastric Cancer Gastroesophageal Junction Cancer Urothelial Cancer Non Small Cell Lung Cancer Head and Neck Squamous Cell Carcinomas	Drug: PF-07265028 Biological: Sasanlimab	Phase 1

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-07257876 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 24, 2022

Anticipated Primary Completion Date :

Jul 8, 2025

Anticipated Study Completion Date :

Jan 6, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1) [Cycle 1 (28 days)]
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
Number of participants with adverse events (AEs) [Baseline through up to 2 years]
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.
Number of participants with clinically significant laboratory abnormalities [Baseline through up to 2 years]
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Objective response rate (ORR) in Dose Expansion (Part 2) [Baseline through up to 2 years or until disease progression]
Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Across all cohorts:

Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Adequate hematological, kidney and liver function
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Resolved acute effects of any prior therapy
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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute	Scottsdale	Arizona	United States	85258
2	HonorHealth Scottsdale Shea Medical Center	Scottsdale	Arizona	United States	85260
3	START Midwest	Grand Rapids	Michigan	United States	49546
4	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas	United States	78229
5	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas	United States	78229
6	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
7	The Cancer Institute Hospital of JFCR	Koto	Tokyo	Japan	135-8550