To determine the activity and safety of 177 Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression; and to identify potential prognostic and predictive biomarkers from imaging, blood, and tissue.
ENZA-p (ANZUP 1901) is an open-label, randomised, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone OR enzalutamide plus 177 Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177 Lu-PSMA-617 doses are allowed, informed by a Day 92 68 Ga-PSMA PET (up to 4 doses in total). The primary endpoint is PSA progression-free survival (PFS); other major endpoints include radiological PFS, PSA response rate, overall survival, health related quality of life (HRQOL), adverse events and cost-effectiveness. Key eligibility criteria include biochemical and/or clinical progression; 68 Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Imaging is with RECIST imaging 12 weekly; 68 Ga-PSMA PET at baseline, Days 15, 92, and progression; and, 18 F FDG PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA and 18 F FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants providing 80% power with a 2-sided type-1 error rate of 5% to detect a HR of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone.
and Conclusion: The combination of 177 Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.
BJU international. 2021 May 24 [Epub ahead of print]
Louise Emmett, Shalini Subramaniam, Anthony Joshua, Megan Crumbaker, Andrew Martin, Alison Y Zhang, Nisha Rana, Ailsa Langford, Jenna Mitchell, Sonia Yip, Roslyn Francis, Michael S Hofman, Shahneen Sandhu, Arun Azad, Craig Gedye, Margaret McJannett, Martin R Stockler, Ian D Davis, Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) and the ENZA-p investigators
Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, Australia., NHMRC Clinical, Trials Centre, University of Sydney, Sydney, Australia., Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, Australia., Garvan Institute of Medical Research, Sydney, Australia., Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, Australia., Sir Charles Gairdner Hospital, Perth, Australia., Sir Peter MacCallum, Department of Oncology, The University of Melbourne, Melbourne, Australia., Calvary Mater Newcastle, Australia., Eastern Health Clinical School, Monash University, Melbourne, Australia.