KEY TAKEAWAYS
- The LuPARP phase I trial aimed to evaluate the safety and effectiveness of a new combination treatment for advanced prostate cancer.
- The primary objectives were establishing the DLTs and RP2D. Secondary objectives include toxicity, rPFS, PSA50-RR, PSA-PFS, ORR, and OS.
- The study found that a new combination treatment for advanced prostate cancer was well tolerated and showed promise.
Anew treatment for advanced prostate cancer, 177Lu-PSMA-617, has shown promise in improving survival. However, some patients(pts) do not respond to the treatment, and all pts eventually relapse. Olaparib, a drug that blocks DNA repair, may be effective when combined with 177Lu-PSMA-617.
Researchers aimed to evaluate the safety and effectiveness of a new combination treatment for advanced prostate cancer.
The study involved 48 pts with metastatic castration-resistant prostate cancer(mCRPC) and high PSMA expression; pts enrolled in two stages of dose-escalation (using a standard 3+3 design) and dose-expansion at the recommended phase 2 dose (RP2D). Pts administered with 177Lu-PSMA-617 intravenously at 7.4 GBq on day 1, every 6 weeks for up to 6 cycles, along with olaparib following specified dose schedules. The dose-limiting toxicity (DLT) assessment period is 6 weeks. The primary objectives were to identify DLTs and determine the RP2D. Secondary objectives include evaluating toxicity, radiological progression-free survival (rPFS), PSA response rate (PSA50-RR), PSA progression-free survival (PSA-PFS), objective response rate (ORR), and overall survival (OS). Responses were assessed through PSA measurements and imaging with PET/CT scans every 12 weeks, including PSMA PET/CT.
Of 29 pts (median age: 70 years; range: 52-84; prior docetaxel: 97%; prior androgen receptor pathway inhibitor: 100%), they received 177Lu-PSMA-617 on day 1 with escalating doses of olaparib (cohorts 1-6: 50mg – 300 mg BD days 2-15) or alternate olaparib schedules (cohort 7: 200 BD days – 4 to 14; cohort 8: 300 BD days – 4 to 14; cohort 9: 300 mg BD days -4 to 18) for up to 6 cycles. No DLTs were reported. Common treatment-related adverse events (TRAE) (≥10%) were Grade (G) 1-2 and included xerostomia (83%), nausea (62%), fatigue (34%), constipation (31%), anorexia (17%), vomiting (14%), and diarrhea (10%). Hematologic TRAE included anemia (G1: 14%; G2: 7%; G3: 7%), thrombocytopenia (G1: 14%; G2: 7%; G3: 3%), and neutropenia (G1: 3%; G3: 7%) that were transient and without clinical sequelae. Across cohorts 1-9, the PSA50-RR was 62% (18/29), and PSA90-RR was 48% (14/29). Five of the 7 pts (71%) with RECIST measurable disease had a partial response.
The study found that a new combination treatment for advanced prostate cancer was well tolerated and showed promise. Dose expansion is delayed until RP2D is confirmed by enrolling 3 more pts in cohort 9.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.5005
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03874884
Shahneen Sandhu, Anthony M. Joshua, Louise Emmett, Megan Crumbaker, Mathias Bressel, Rhonda Huynh, Patricia Diana Banks, Roslyn Wallace, Anis Hamid, Andrisha Jade Inderjeeth, Ben Tran, Arun Azad, Ramin Alipour, Grace Kong, Aravind Ravi Kumar, Javad Saghebi, Scott Williams, Timothy J. Akhurst, Rodney J. Hicks, and Michael S Hofman. DOI: 10.1200/JCO.2023.41.16_suppl.5005 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 5005-5005.
