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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors, Gastric Cancer, Gastroesophageal Junction Cancer, Urothelial Cancer, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinomas

Intervention / Treatment
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* Drug: PF-07265028
* Biological: Sasanlimab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A Dose Escalation Monotherapy<br>Participants will receive PF-07265028 at escalating dose levels. | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>|
| Experimental: Part 1B Dose Escalation Combination<br>Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (SCCHN)<br>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<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (UC)<br>Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (Gastric/GEJ)<br>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<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (NSCLC)<br>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<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (selected tumor types)<br>Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2B Dose Expansion Monotherapy (selected tumor types)<br>Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A. | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, advanced solid tumor, metastatic solid tumor, first in human, Gastric cancer, Gastroesophageal junction cancer, Urothelial Cancer, Non small cell lung cancer, Head and neck squamous cell carcinomas, SCCHN, NSCLC, Lung cancer, Hematopoietic progenitor kinase 1 inhibitor, HPK1 inhibitor