644TiP SAABR: Single arm phase II study of abiraterone + atezolizumab + GnRH analog and stereotactic body radiotherapy (SBRT) to the prostate in men with newly diagnosed hormone-sensitive metastatic prostate cancer (mHSPC)

Abstract

Several phase III trials have demonstrated that adding the androgen synthesis inhibitor abiraterone acetate (AA) to androgen deprivation therapy (ADT) offers a survival benefit for men with mHSPC. Moreover, 1) outcomes in subjects with locally advanced disease enrolled on STAMPEDE suggest that prostate radiation therapy may be associated with a reduction in treatment failure and 2) preclinical studies have shown that SBRT can induce an immunogenic effect through enhanced expression of the PD-L1 protein on tumor and immune cells. Therefore, combining androgen ablation (AA + ADT) with the cytotoxic and immune properties of SBRT and the additional effects of atezolizumab (ATEZO), an anti-PD-L1 immunotherapy, could be a new treatment approach with potential synergistic effects. The primary objective is to evaluate the failure-free rate at 2 years (binary endpoint). Failure is defined as biochemical failure; radiographic progression (as defined by PCWG3); or death from any cause. ATEZO will be administered to men with newly diagnosed mHSPC by IV infusion (1200 mg IV over 60 minutes every 3 weeks) followed after Cycle 1 by AA (1000 mg PO every day with prednisone 5 mg daily), ADT (GnRH analog), and SBRT (7.25-7.50 Gy x 5 fractions to prostate and seminal vesicles every other day starting at Cycle 5 Day 1 ± 5 days) until unacceptable toxicity, protocol defined progression, or 2 years of treatment. ATEZO will be continued for a maximum of 2 years. Continuation of AA and ADT beyond 2 years is at the discretion of the treating physician per local standard of care. For the first 20 patients, a biopsy will be done after initiation of ATEZO but before AA; for the final 22 patients, biopsy will be done while on both ATEZO and AA, but before SBRT. Biopsy results at diagnosis and on treatment will be compared for correlative analyses. Up to 10 subjects who initiated treatment on GnRH analog prior to treatment consent will be enrolled. 10 of the planned 42 evaluable subjects have been enrolled. PCCTC-managed; Genentech-funded. NCT04262154. Memorial Sloan Kettering Cancer Center.