Phase 1b/2 Study of PF-08634404 Monotherapy and Combination Therapy in Adults with Locally Advanced or Metastatic Renal Cell Carcinoma

The primary objectives of this study are to evaluate the antitumor activity, safety, and tolerability of PF-08634404 as a monotherapy or in combination with ipilimumab or axitinib in adults with locally advanced or metastatic renal cell carcinoma. Additionally, the study aims to identify the optimal dose of PF-08634404 when administered in combination with these agents.

Secondary objectives include:

• Assessment of additional efficacy measures for PF-08634404 in both monotherapy and combination regimens.
• Evaluation of further safety and tolerability parameters.
• Characterization of the pharmacokinetics of PF-08634404.
• Investigation of the immunogenicity of PF-08634404.

This study involves 174 participants diagnosed with advanced or metastatic renal cell carcinoma. The study population includes both male and female individuals within specific age ranges. Eligible participants must be at least 18 years of age and possess a diagnosis confirmed by histology or cytology. Inclusion requires the presence of at least one untreated, measurable lesion and an Eastern Cooperative Oncology Group performance status of 0 or 1. Participants must demonstrate adequate hematologic, hepatic, cardiac, and renal function across all International Metastatic Renal Cell Carcinoma Database Consortium risk categories. Prior systemic therapy for this condition is excluded, although immunotherapy administered more than 12 months after surgery is permitted.

This interventional Phase 1b/2 study is designed to evaluate the safety and efficacy of PF-08634404 administered as monotherapy or in combination with other anticancer agents in adults with renal cell carcinoma. The research is organized into three distinct cohorts: Cohort A investigates PF-08634404 alone, Cohort B evaluates the combination of PF-08634404 and ipilimumab, and Cohort C assesses the combination of PF-08634404 and axitinib. The methodology involves two parts, where Part 1 focuses on assessing dose-limiting toxicities and safety, and Part 2 aims to identify the optimal dose for combination therapies. Primary endpoints include the objective response rate as determined by RECIST 1.1 and the characterization of adverse events using NCI CTCAE criteria. Secondary objectives involve monitoring progression-free survival, overall survival, and the incidence of antidrug antibodies. Participants must undergo a screening process to confirm eligibility based on histological diagnosis, measurable lesions, and adequate organ function. The trial is estimated to conclude by November 2028.

PF-08634404 is administered as a concentrate for solution for infusion via intravenous administration. This agent is evaluated both as a monotherapy and in combination with other anticancer agents in participants with renal cell carcinoma.

Ipilimumab is administered through intravenous use as part of combination therapy regimens.

Axitinib is administered via the oral route for use in combination therapy.

Efficacy assessment for participants with renal cell carcinoma focuses on determining antitumor activity through various endpoints. In Cohort A, the primary efficacy endpoint is the confirmed objective response rate (ORR). Secondary efficacy parameters include duration of response (DoR), progression-free survival (PFS), and overall survival (OS). For Cohorts B and C, the confirmed ORR serves as a primary endpoint, while DoR, PFS, and OS are utilized as secondary endpoints.

The evaluation of tumor response is conducted using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator. Additional secondary assessments include the monitoring of predose and post dose concentrations of PF-08634404 and the incidence of antidrug antibodies (ADA).