Imbassador250: A Phase Iii Trial Comparing Atezolizumab With Enzalutamide Vs Enzalutamide Alone In Patients With Metastatic Castration-Resistant Prostate Cancer (Mcrpc)

Background: Current treatments for mCRPC include the androgen receptor antagonist enzalutamide (enza). Enza may enhance IFNγ signaling and sensitize tumor cells to immune-mediated cell killing, making it a candidate for combinations with PD-L1/PD-1 inhibitors. Responses have been observed in patients (pts) with mCRPC receiving a PD-L1/PD-1 inhibitor with or without enza. Therefore, atezolizumab (atezo), a humanized anti-PD-L1 monoclonal antibody that inhibits the interaction between PD-L1 and its receptors, is being examined in combination with enza for pts with mCRPC. Methods: IMbassador250 was a Phase III, randomized clinical trial (NCT03016312) evaluating the safety and efficacy of atezo + enza vs enza alone in pts with mCRPC who had progressed on abiraterone and docetaxel, or were not candidates for a taxane regimen (androgen deprivation therapy was not given). Eligible pts had mCRPC or locally advanced, incurable CRPC, ECOG PS 0/1 and no prior immunotherapy or enza/androgen receptor antagonist treatment. After a safety run-in, pts were randomized 1:1 to receive atezo 1200 mg every 3 weeks + enza 160 mg once daily or enza 160 mg once daily only. Stratification factors were prior taxane treatment, presence of liver metastases, level of circulating LDH and pain. The primary endpoint was OS; secondary endpoints included PSA response rate, radiographic PFS, ORR and safety. Tumor tissue and disease progression will be used to assess the relationship between exploratory biomarkers and treatment response. Results: A total of 759 pts were randomized to atezo + enza (n = 379) or enza alone (n = 380). Baseline demographic and clinical characteristics were generally similar between groups. The primary efficacy endpoint of OS was evaluated (data cutoff for efficacy and safety, June 24, 2019), with no difference observed between groups (stratified HR, 1.12 [95% CI: 0.91, 1.37]; P = 0.28). Median OS was 15.2 months (95% CI: 14.0, 17.0) in the atezo + enza group and 16.6 months (95% CI: 14.7, 18.4) in the enza group. Subgroup analyses were consistent with the primary endpoint. Analyses of secondary and exploratory endpoints are ongoing and will be presented. Adverse events (AEs) were consistent with those seen with the treatment components. Nearly all pts had an AE (atezo + enza, 96.5%; enza alone, 91.8%). Treatment-related AEs (TRAEs) were observed in 77.8% and 51.1% of pts, respectively, with Grade 3-4 TRAEs in 28.3% and 9.6% and Grade 5 TRAEs in 1.9% and 0.3% of pts. Conclusions: The combination of atezo + enza did not show an OS improvement vs enza alone, requiring early termination of the study. The observed safety profiles were consistent with the known safety profiles of each treatment. Analyses of secondary outcomes and exploratory endpoints, biomarker studies and treatment response may provide further insight into these findings. Citation Format: Christopher J. Sweeney, Silke Gillessen, Dana Rathkopf, Nobuaki Matsubara, Charles Drake, Karim Fizazi, Josep M. Piulats, Piotr J. Wysocki, Gary L. Buchschacher Jr, Jennifer Doss, Sanjeev Mariathasan, Edward E. Kadel, Kobe Yuen, Asim Datye, Grozdana Rasuo, Darren Tayama, Patrick Williams, Thomas Powles. IMbassador250: A phase III trial comparing atezolizumab with enzalutamide vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT014.