Clinical trial NCT05233436: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1)
timeFrame: Cycle 1 (28 days)
measure: Number of participants with adverse events (AEs)
timeFrame: Baseline through up to 2 years
measure: Number of participants with clinically significant laboratory abnormalities
timeFrame: Baseline through up to 2 years
measure: Objective response rate (ORR) in Dose Expansion (Part 2)
timeFrame: Baseline through up to 2 years or until disease progression
Secondary outcomes:
measure: The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax.
timeFrame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
measure: The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax.
timeFrame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
measure: The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC
timeFrame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
measure: The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax.
timeFrame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
measure: The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax
timeFrame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
measure: The effect of food on the pharmacokinetic profile of PF-07265028 through AUC
timeFrame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days)
measure: The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin
timeFrame: 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)
measure: The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb
timeFrame: 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)
measure: The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation
timeFrame: Baseline through up to 2 years
measure: ORR in Dose Escalation (Part 1)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
measure: Time to event endpoints (DOR) in Dose Expansion (Part 2)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
measure: Time to event endpoints (PFS) in Dose Expansion (Part 2)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
measure: Time to event endpoints (OS) in Dose Expansion (Part 2)
timeFrame: From baseline through disease progression or study completion (approximately 2 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Shea Medical Center
state: Arizona
city: Margate
country: United States
facility: D&H Cancer Research Center LLC
state: Florida
city: Margate
country: United States
facility: Napa Research
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Dallas
country: United States
facility: Mary Crowley Cancer Research - Medical City Hospital
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Koto
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: