Efficacy and safety of the DLL3 T-cell engager gocatamig in participants (pts) with neuroendocrine prostate cancer (NEPC) and other neuroendocrine neoplasms (NEN).

Abstract

182 Background: Genitourinary neuroendocrine carcinomas (GU NEC), including small cell carcinoma of the bladder (SCCB) and NEPC, are highly aggressive NEN with poor prognosis and limited treatment options. Delta-like ligand 3 (DLL3) expression is frequently upregulated in NEPC and other high-grade NEN and not expressed in normal tissues. Gocatamig (MK-6070; HPN328) is a DLL3-targeting T-cell engager. Gocatamig monotherapy has shown promising clinical activity and manageable safety in the treatment of DLL3-expressing tumors, including small cell lung cancer. Here we report updated results for pts with NEPC and other NEN treated with gocatamig monotherapy in the ongoing phase 1/2 study MK-6070-001 (NCT04471727). Methods: Pts with relapsed/refractory, metastatic NEPC or other high-grade DLL3-expressing NEN received gocatamig IV monotherapy step-up dosing followed by target doses (6, 12, or 24 mg) every 1 or 2 weeks (QW or Q2W). DLL3-positivity (defined by immunohistochemistry staining of >0% tumor cells) was required for other NEN but not NEPC. Efficacy was evaluated by investigator assessed objective response rate (ORR) per RECIST v1.1. Results: As of 28FEB2025, 20 pts with NEPC and 37 with other NEN, including 12 with SCCB, received gocatamig. The median (range) prior lines of therapy were 3 (1-7) for NEPC and 2 (1-6) for other NEN. Most (93%) pts had received prior platinum-based chemotherapy. Median (range) follow-up was 7.3 (0.8-24.4) months (mo) for pts with NEPC and 6.3 (0.7-26.6) mo for pts with other NEN. Treatment is ongoing for 34 (60%) pts. Across all dose groups, the confirmed objective response rate (ORR) was 15% (95% CI 3-38) for pts with NEPC and 46% (95% CI 30-63) for pts with other NEN. The confirmed ORR for pts in the 24 mg Q2W cohort was 29% (95% CI 4-71) for pts with NEPC (n=7) and 50% (95% CI 21-79) for pts with other NEN (n=12). The median duration of response was not reached for NEPC (range 3.7-7.8+ mo) or other NEN (1.8+-11.8+ mo). Any grade/grade 3-4 treatment-related (TR) AEs occurred in 100%/40% of all pts with NEPC and 97%/53% of all pts with other NEN. There were no grade 5 TRAEs. DLL3 was expressed in 15 of 17 (88%) NEPC available for analysis, and response to gocatamig did not correlate with DLL3 expression levels; data for other NEN are pending and will be presented. In addition, updated results will be presented for pts with NEPC and other NEN, including pts with SCCB. Conclusions: Gocatamig continues to show encouraging clinical activity with a manageable safety profile in pts with heavily pretreated NEN, including confirmed, durable responses in NEPC. Clinical trial information: NCT04471727 .