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

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

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.

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.

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