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

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05233436
• Other study ID #: C4731001
• Status: Terminated
• Phase: Phase 1
• Start date: February 24, 2022
• Est. completion date: October 16, 2023

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: October 16, 2023
• Est. primary completion date: October 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Gastric Cancer
• Gastroesophageal Junction Cancer
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• Stomach Neoplasms
• Urothelial Cancer

Intervention

Drug:
• PF-07265028
PF-07265028 will be administered orally

Biological:
• Sasanlimab
Administered subcutaneously

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	The Cancer Institute Hospital of JFCR	Koto	Tokyo
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Mary Crowley Cancer Research - Medical City Hospital	Dallas	Texas
United States	START Midwest	Grand Rapids	Michigan
United States	University of Iowa	Iowa City	Iowa
United States	D&H Cancer Research Center LLC	Margate	Florida
United States	Napa Research	Margate	Florida
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 Research Institute	Scottsdale	Arizona
United States	HonorHealth Scottsdale Shea Medical Center	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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