ASCO 2017: A phase III trial comparing atezolizumab with enzalutamide vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer

Chicago, IL (UroToday.com) Selecting the appropriate sequence and combination of therapy for metastatic castration-resistant prostate cancer (mCRPC) is challenging. At the ASCO 2017 prostate cancer poster session, Dr. Thomas Powles and colleagues presented their study design for a phase III trial comparing atezolizumab with enzalutamide versus enzalutamide alone in patients with mCRPC (IMbassador250 Trial).

Despite advances in the agents available in the mCRPC setting, in particular approval of abiraterone and enzalutamide, most patients experience disease progression and there is inadequate data to guide the sequencing of agents to optimize outcomes.

Patients with mCRPC who progress on enzalutamide have increased circulating PD-L1/PD-L2–positive dendritic cells compared with enzalutamide-naive patients or patients who are still responding to treatment.1 Furthermore, PSA and radiographic responses were observed in mCRPC patients treated with a PD-L1/PD-1 pathway inhibitor with or without enzalutamide.2 Atezolizumab is an anti–PD-L1 monoclonal antibody that inhibits the interaction between PD-L1 and its receptors, PD-1 and B7.1, enhancing T-cell responses and improving anti-tumor activity. The objective of this study was to assess the effectiveness of combination atezolizumab and enzalutamide as a potential treatment option for mCRPC patients.

In this phase III, randomized, multicenter, clinical trial, atezolizumab + enzalutamide compared to enzalutamide alone will include patients who have received prior abiraterone treatment and have progressed on, are ineligible for, or have refused a taxane regimen. Eligible patients will have mCRPC or locally advanced incurable CRPC and ECOG performance status 0-1. These patients will then be randomized 1:1 to receive atezolizumab 1200 mg every 3 weeks and enzalutamide 160 mg each day or enzalutamide alone. The primary endpoint is OS, and secondary endpoints include PSA response rate, rPFS, ORR and safety. Exploratory biomarkers associated with responses to atezolizumab and enzalutamide will be evaluated in tumor tissue collected at baseline and progression.

This study is currently enrolling patients, aiming for 558 patients across 150 sites around the world.
Clinical trial: NCT03016312

Presented By: Thomas Powles, MD, Barts Cancer Institute, London, UK

Co-Authors: Karim Fizazi, Silke Gillessen, Charles G. Drake, Dana E. Rathkopf, Sujata Narayanan, Marjorie C. Green, Almut Mecke, Christina Schiff, Christopher Sweeney

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA

REFERENCES:
1. Biship JL, Sio A, Angeles A, et al. PD-L1 is highly expressed in enzalutamide resistant prostate cancer. Oncotarget 2015 Jan 1;6(1):234-242.

2. Graff JN, Alumkal JJ, Drake CG, et al. Early evidence of anti-PD-1 activity in enzalutamide resistance prostate cancer. Oncotarget 2016 Aug 16;7(33):52810-52817.
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