AtezoCab: A phase II study of cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with non-measurable disease (NMD).

Abstract

TPS295 Background: Preclinical studies and clinical observations suggest that C promotes an immune permissive environment, which might lead to synergistic effects from combination treatment with immune checkpoint inhibitors. In Cohort 6 of COSMIC-021 study, the combination of C and A showed encouraging clinical activity and acceptable tolerability in mCRPC pts who had radiographically progressed in soft tissue on or after novel hormonal treatment (NHT; PMID: 35690072). CONTACT-02 is a phase 3 study randomizing pts with mCRPC with measurable disease 1:1 to C+A or NHT (NCT04446117). The objective of this study is to specifically evaluate the safety and efficacy of C+A in pts with mCRPC with NMD. Methods: AtezoCab is an IRB approved, investigator-initiated, single-arm, single-center, open-label, non-randomized phase 2 study of C+A in mCRPC patients with NMD to assess disease control rate (DCR). Treatment: C 40 mg oral daily + A 1200 mg intravenously every 3 weeks. Treatment continues until progression or intolerable toxicities. Key inclusion criteria: ≥18 years age, mCRPC with histologically or cytologically confirmed adenocarcinoma without small cell histology, Eastern Cooperative Oncology Group performance status ≤ 2, adequate organ function, prior treatment with NHT, only NMD outside the pelvis (above aortic bifurcation) per RECIST 1.1 criteria. Key exclusion criteria: prior chemotherapy for mCRPC, prior treatment with C, immune checkpoint inhibitors or other systemic immunostimulatory agents, active or history of clinically significant autoimmune disease per treating physician, corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Primary endpoint: Percentage of pts with disease control. DCR will be defined as the percentage of pts with confirmed response of any duration or stable disease or noncomplete response or nonprogressive disease for 24 weeks or longer per PCWG3-modified RECIST v1.1. Up to 33 pts will be enrolled for a total of 30 evaluable pts. This will ensure that DCR can be estimated via a 95% confidence interval (CI) with margin of error <0.18. The primary analysis CI on DCR will be based on Wilson’s approach. Secondary Endpoints: Progression-free survival (PSA and radiographic), PSA50% response rate, overall survival and safety. Tissue and blood samples will be collected for correlative studies. 7 patients have been enrolled. Clinical trial information: NCT05168618 .