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

Pfizer

Status and phase: Terminated; Phase 1

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

Treatments: Drug: PF-07265028; Biological: Sasanlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05233436

C4731001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 8 patient groups

Part 1A Dose Escalation Monotherapy

Experimental group

Description:

Participants will receive PF-07265028 at escalating dose levels.

Treatment:

Drug: PF-07265028

Part 1B Dose Escalation Combination

Experimental group

Description:

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

Treatment:

Biological: Sasanlimab

Drug: PF-07265028

Part 2A Dose Expansion Combination (SCCHN)

Experimental group

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

Treatment:

Biological: Sasanlimab

Drug: PF-07265028

Part 2A Dose Expansion Combination (UC)

Experimental group

Description:

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

Treatment:

Biological: Sasanlimab

Drug: PF-07265028

Part 2A Dose Expansion Combination (Gastric/GEJ)

Experimental group

Description:

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

Treatment:

Biological: Sasanlimab

Drug: PF-07265028

Part 2A Dose Expansion Combination (NSCLC)

Experimental group

Description:

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

Treatment:

Biological: Sasanlimab

Drug: PF-07265028

Part 2A Dose Expansion Combination (selected tumor types)

Experimental group

Description:

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

Treatment:

Biological: Sasanlimab

Drug: PF-07265028

Part 2B Dose Expansion Monotherapy (selected tumor types)

Experimental group

Description:

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

Treatment:

Drug: PF-07265028