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

Primary Purpose

Advanced Solid Tumors, Gastric Cancer, Gastroesophageal Junction Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PF-07265028
Sasanlimab
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumors focused on measuring 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

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • HonorHealth Research InstituteRecruiting
  • HonorHealth Scottsdale Shea Medical CenterRecruiting
  • D&H Cancer Research Center LLCRecruiting
  • Napa Research
  • University of IowaRecruiting
  • START MidwestRecruiting
  • Mary Crowley Cancer Research - Medical City HospitalRecruiting
  • South Texas Accelerated Research Therapeutics (START)Recruiting
  • South Texas Accelerated Research Therapeutics, LLCRecruiting
  • National Cancer Center Hospital EastRecruiting
  • The Cancer Institute Hospital of JFCRRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1A Dose Escalation Monotherapy

Part 1B Dose Escalation Combination

Part 2A Dose Expansion Combination (SCCHN)

Part 2A Dose Expansion Combination (UC)

Part 2A Dose Expansion Combination (Gastric/GEJ)

Part 2A Dose Expansion Combination (NSCLC)

Part 2A Dose Expansion Combination (selected tumor types)

Part 2B Dose Expansion Monotherapy (selected tumor types)

Arm Description

Participants will receive PF-07265028 at escalating dose levels.

Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose

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

Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B

Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B

Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B

Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B

Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A.

Outcomes

Primary Outcome Measures

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
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.
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.
Objective response rate (ORR) in Dose Expansion (Part 2)
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.
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.
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
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.
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
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
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
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
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
Levels of intratumor T cells and PD-L1 expression in pre- and post-treatment tumor biopsies
ORR in Dose Escalation (Part 1)
Tumor response assessment based on RECIST 1.1
Time to event endpoints (DOR) in Dose Expansion (Part 2)
Duration of response (DOR) as assessed using RECIST 1.1.
Time to event endpoints (PFS) in Dose Expansion (Part 2)
Progression free survival (PFS) as assessed using RECIST 1.1.
Time to event endpoints (OS) in Dose Expansion (Part 2)
Overall survival (OS) assessed proportion of patients alive

Full Information

First Posted
January 6, 2022
Last Updated
October 5, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT05233436
Brief Title
PF-07265028 As Single Agent And In Combination With Sasanlimab in Advanced or Metastatic Solid Tumors
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 24, 2022 (Actual)
Primary Completion Date
July 27, 2026 (Anticipated)
Study Completion Date
January 25, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors, Gastric Cancer, Gastroesophageal Junction Cancer, Urothelial Cancer, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinomas
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1A Dose Escalation Monotherapy
Arm Type
Experimental
Arm Description
Participants will receive PF-07265028 at escalating dose levels.
Arm Title
Part 1B Dose Escalation Combination
Arm Type
Experimental
Arm Description
Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose
Arm Title
Part 2A Dose Expansion Combination (SCCHN)
Arm Type
Experimental
Arm Description
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
Arm Title
Part 2A Dose Expansion Combination (UC)
Arm Type
Experimental
Arm Description
Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Arm Title
Part 2A Dose Expansion Combination (Gastric/GEJ)
Arm Type
Experimental
Arm Description
Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Arm Title
Part 2A Dose Expansion Combination (NSCLC)
Arm Type
Experimental
Arm Description
Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Arm Title
Part 2A Dose Expansion Combination (selected tumor types)
Arm Type
Experimental
Arm Description
Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
Arm Title
Part 2B Dose Expansion Monotherapy (selected tumor types)
Arm Type
Experimental
Arm Description
Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A.
Intervention Type
Drug
Intervention Name(s)
PF-07265028
Intervention Description
PF-07265028 will be administered orally
Intervention Type
Biological
Intervention Name(s)
Sasanlimab
Other Intervention Name(s)
PF-06801591
Intervention Description
Administered subcutaneously
Primary Outcome Measure Information:
Title
Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1)
Description
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
Time Frame
Cycle 1 (28 days)
Title
Number of participants with adverse events (AEs)
Description
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.
Time Frame
Baseline through up to 2 years
Title
Number of participants with clinically significant laboratory abnormalities
Description
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Time Frame
Baseline through up to 2 years
Title
Objective response rate (ORR) in Dose Expansion (Part 2)
Description
Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame
Baseline through up to 2 years or until disease progression
Secondary Outcome Measure Information:
Title
The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax.
Description
Maximum observed plasma concentration of PF-07265028 (Cmax) and Maximum observed steady state plasma concentration (Cmax, ss)
Time Frame
Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
Title
The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax.
Description
Time to maximal observed plasma concentration of PF-07265028 (Tmax) and Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).
Time Frame
Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
Title
The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC
Description
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)
Time Frame
Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
Title
The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax.
Description
Maximum observed plasma concentration of PF-07265028 (Cmax) under fasted and fed conditions in the subset of participants
Time Frame
Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
Title
The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax
Description
Time to maximal observed plasma concentration of PF-07265028 (Tmax) under fasted and fed conditions in the subset of participants
Time Frame
Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
Title
The effect of food on the pharmacokinetic profile of PF-07265028 through AUC
Description
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
Time Frame
Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
Title
The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin
Description
Minimum plasma concentration (Cmin) will be calculated through the measured pre-dose plasma concentration
Time Frame
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)
Title
The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb
Description
Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against sasanlimab
Time Frame
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)
Title
The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation
Description
Levels of intratumor T cells and PD-L1 expression in pre- and post-treatment tumor biopsies
Time Frame
Baseline through up to 2 years
Title
ORR in Dose Escalation (Part 1)
Description
Tumor response assessment based on RECIST 1.1
Time Frame
From baseline through disease progression or study completion (approximately 2 years)
Title
Time to event endpoints (DOR) in Dose Expansion (Part 2)
Description
Duration of response (DOR) as assessed using RECIST 1.1.
Time Frame
From baseline through disease progression or study completion (approximately 2 years)
Title
Time to event endpoints (PFS) in Dose Expansion (Part 2)
Description
Progression free survival (PFS) as assessed using RECIST 1.1.
Time Frame
From baseline through disease progression or study completion (approximately 2 years)
Title
Time to event endpoints (OS) in Dose Expansion (Part 2)
Description
Overall survival (OS) assessed proportion of patients alive
Time Frame
From baseline through disease progression or study completion (approximately 2 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pfizer CT.gov Call Center
Phone
1-800-718-1021
Email
ClinicalTrials.gov_Inquiries@pfizer.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
HonorHealth Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Recruiting
Facility Name
HonorHealth Scottsdale Shea Medical Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85260
Country
United States
Individual Site Status
Recruiting
Facility Name
D&H Cancer Research Center LLC
City
Margate
State/Province
Florida
ZIP/Postal Code
33063
Country
United States
Individual Site Status
Recruiting
Facility Name
Napa Research
City
Margate
State/Province
Florida
ZIP/Postal Code
33063
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Name
START Midwest
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49546
Country
United States
Individual Site Status
Recruiting
Facility Name
Mary Crowley Cancer Research - Medical City Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Individual Site Status
Recruiting
Facility Name
South Texas Accelerated Research Therapeutics (START)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
South Texas Accelerated Research Therapeutics, LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Individual Site Status
Recruiting
Facility Name
The Cancer Institute Hospital of JFCR
City
Koto
State/Province
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4731001
Description
To obtain contact information for a study center near you, click here.

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

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