A phase Ia study of safety and clinical activity of atezolizumab (atezo) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

187 Background: In the past decade, several therapies have been approved for mCRPC. However, most pts develop resistance and experience disease progression. Thus, there remains a high unmet need. Atezo (anti–PD-L1) blocks the interaction between PD-L1 and its receptors, PD-1 and B7.1, thereby restoring anti-tumor immunity. Atezo has demonstrated clinical efficacy in many tumor types. Here we report the clinical safety and activity of atezo in pts with mCRPC from a Phase Ia study (PCD4989g; NCT01375842). Methods: Eligible pts previously received enzalutamide and/or sipuleucel-T for mCRPC. Pts also had PSA or radiographic progression prior to enrollment. Atezo 1200mg was administered IV q3w. CT and bone scans were performed q6w for 24w and q12w thereafter (q6w if treatment beyond disease progression). Primary objectives were safety and tolerability; OS was an exploratory objective. mCRPC cohort–specific objectives included PSA response, radiographic progression per PCWG2 criteria, soft tissue response per RECIST v1.1 and immune-related response criteria (irRC). Survival follow-up data was collected ≈ every 3 mo until death or loss to follow-up. Results: The 15 pts in the initial mCRPC cohort were evaluated (clinical cutoff: December 31, 2016). 13 pts (87%) had received ≥ 2 prior lines of therapy for mCRPC. Median survival follow-up was 15.8 mo (range, 2.3-23.0). 9 pts (60%) had a treatment-related AE (TRAE); only 1 pt (7%) experienced a Gr 3 TRAE (hyponatremia). No Gr 4-5 TRAEs were reported. The landmark 12-mo OS rate was 55.6% (95% CI: 27.4, 83.7); median OS was not reached (range, 2.3-23.0 mo). Median PFS was 3.4 mo (95% CI: 2.3, 5.7); the 6-mo PFS rate was 26.7% (95% CI: 4.3, 49.1). 1 pt (9%) had a PR per irRC (irPR); 5 pts (45%) had SD per RECIST v1.1 and irRC. 2 pts (13%) had a ≥ 50% decrease in PSA from baseline. The pt who experienced an irPR had increased CD8 expression and expansion of T-cell clones on study treatment. Conclusions: Atezo was well tolerated and demonstrated long-term disease control in pts with heavily pretreated mCRPC, with a 12-mo OS rate of 55.6%. Preliminary biomarker analyses from the pt who experienced an irPR were suggestive of an activated immune response. Clinical trial information: NCT01375842.