KEY TAKEAWAYS
- The study aimed to investigate 177Lu-PNT2002’s efficacy in PSMA-positive in patienst with mCRPC after ARPI failure.
- The primary endpoint was to determine rPFS and BICR.
- Researchers noted that 177Lu-PNT2002 improved outcomes in PSMA-positive mCRPC compared to ARPI.
The metastatic castration-resistant prostate cancer (mCRPC) is a life-threatening condition with significant unmet needs. 177Lu-PNT2002 is a beta-emitting radioisotope attached to a small-molecule ligand that targets PSMA.
Oliver Sartor and the team aimed to assess the efficacy and safety of 177Lu-PNT2002 in patients with PSMA-positive mCRPC.
They performed an inclusive analysis in the SPLASH open-label Phase 3 trial, which enrolled PSMA PET-positive patients with mCRPC who had progressed on 1 ARPI and had not received chemotherapy for castration-resistant disease. Patients were randomized 2:1 to receive either 177Lu-PNT2002 (6.8 GBq IV every 8 weeks for up to 4 cycles) or an alternate ARPI.
The primary endpoint was radiographic progression-free survival (rPFS), assessed by blinded independent central review (BICR) using RECIST 1.1/PCWG3 criteria. Additional key endpoints included overall survival (OS), objective response rate (ORR), PSA50, HRQoL, and safety. Crossover from the alternate ARPI to 177Lu-PNT2002 was permitted upon confirmation of disease progression by BICR.
About 488 patients were screened with PSMA PET, of whom 90.4% were PSMA positive. A total of 412 patients were randomized to receive either 177Lu-PNT2002 (n=276, median 4 cycles) or an alternate ARPI (n=136). Demographics and baseline characteristics were well balanced between the 177Lu-PNT2002 and ARPI groups: ECOG status 0 was 58.7% vs. 55.9%, and M0 status was 10.1% vs. 11.0%, respectively.
The crossover rate was 84.6% (77/91). The primary endpoint of rPFS was improved in patients receiving 177Lu-PNT2002 (9.5 months, 95% CI: 7.4, 10.0) compared to ARPI (6.0 months, 95% CI: 4.7, 7.9) (HR, 95% CI: 0.71, 0.55, 0.92; P=0.0088). Other efficacy outcomes are provided in the table.
The incidence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation and grade ≥3 TEAEs were both lower with 177Lu-PNT2002 compared to ARPI (1.9% vs. 6.2% and 30.1% vs. 36.9%, respectively). The most common TEAEs with 177Lu-PNT2002 were fatigue (53.5%), dry mouth (37.2%), and nausea (31.2%).
The trial was sponsored by POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/135
Clinical Trial: https://clinicaltrials.gov/study/NCT04647526
Sartor O, Jiang D.M, Smoragiewicz M, et al. (2024). “Efficacy of 177Lu-PNT2002 in PSMA-positive mCRPC following progression on an androgen-receptor pathway inhibitor (ARPI) (SPLASH).” Presented at ESMO 2024 (Abstract LBA65).
