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

Phase 1

Terminated

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

• Registration Number: NCT05233436
• Lead Sponsor: Pfizer

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-01-06
• Study First Submitted QC: 2022-01-31
• Study First Posted: 2022-02-10
• Study Start: 2022-02-24
• Primary Completion: 2023-10-16
• Study Completion: 2023-10-16
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-29
• Last Update Posted: 2024-05-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1A Dose Escalation Monotherapy	PF-07265028	Participants will receive PF-07265028 at escalating dose levels.
Part 1B Dose Escalation Combination	PF-07265028	Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose
Part 1B Dose Escalation Combination	Sasanlimab	Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose
Part 2A Dose Expansion Combination (SCCHN)	PF-07265028	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
Part 2A Dose Expansion Combination (SCCHN)	Sasanlimab	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
Part 2A Dose Expansion Combination (UC)	PF-07265028	Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2A Dose Expansion Combination (UC)	Sasanlimab	Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2A Dose Expansion Combination (Gastric/GEJ)	PF-07265028	Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2A Dose Expansion Combination (Gastric/GEJ)	Sasanlimab	Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2A Dose Expansion Combination (NSCLC)	PF-07265028	Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2A Dose Expansion Combination (NSCLC)	Sasanlimab	Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2A Dose Expansion Combination (selected tumor types)	PF-07265028	Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2A Dose Expansion Combination (selected tumor types)	Sasanlimab	Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Part 2B Dose Expansion Monotherapy (selected tumor types)	PF-07265028	Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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 (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
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
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.

Trial Locations

Locations (12)

Napa Research; 🇺🇸 Margate, Florida, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States

The Cancer Institute Hospital of JFCR; 🇯🇵 Koto, Tokyo, Japan

Mary Crowley Cancer Research - Medical City Hospital; 🇺🇸 Dallas, Texas, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States

South Texas Accelerated Research Therapeutics (START); 🇺🇸 San Antonio, Texas, United States

South Texas Accelerated Research Therapeutics, LLC; 🇺🇸 San Antonio, Texas, United States

HonorHealth Scottsdale Shea Medical Center; 🇺🇸 Scottsdale, Arizona, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

D&H Cancer Research Center LLC; 🇺🇸 Margate, Florida, United States

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Chiba, Japan