Rinatabart sesutecan (Rina-S) for patients with advanced endometrial cancer: First disclosure from dose expansion cohort B2 of the GTC1184-01 study.

3039 Background: Rina-S is an investigational antibody-drug conjugate targeting folate receptor alpha with a novel hydrophilic protease-cleavable linker and a topoisomerase I inhibitor, exatecan payload. Patients (pts) with advanced endometrial cancer (EC) who progress after programmed death-ligand 1 [PD-(L)1] inhibitor plus chemotherapy have very poor prognoses and limited, ineffective treatment options (objective response rate [ORR] < 16% and median progression-free survival < 5 months with single-agent chemotherapy); thus, there is urgent need for novel therapies. In the dose escalation cohort, single-agent Rina-S showed preliminary anti-tumor activity in pts with heavily pretreated EC. Here we first report results for single-agent Rina-S in pts with heavily pretreated EC from dose expansion cohort B2 of the phase 1/2 GCT1184-01 study (NCT05579366). Methods: Pts with metastatic or unresectable EC who received prior platinum-based chemotherapy and a PD-(L)1 inhibitor received either Rina-S 100 mg/m 2 or 120 mg/m 2 every 3 weeks after initial enrollment with 120 mg/m 2 only. The primary endpoint was safety and tolerability of Rina-S. Secondary endpoints included ORR and disease control rate (DCR). Results: As of data cutoff November 22, 2024, 64 pts with heavily pretreated EC (median 3 prior lines [range 1-8]) received Rina-S 100 mg/m 2 (n = 22) or 120 mg/m 2 (n = 42) for a median treatment duration of 15.9 weeks. Most pts had ECOG PS 1 (64.1%), approximately half (46.9%) were aged ≥70 years, and 48.4% had received prior radiotherapy. Pts primarily had endometrioid carcinoma (45.3%) followed by serous carcinoma (26.6%). The most common (> 25%) treatment-emergent adverse events (TEAEs) were similar across doses and were primarily cytopenias and grade 1-2 gastrointestinal events (nausea, vomiting, decreased appetite). Grade 3-4 cytopenia included neutropenia (48.4%), anemia (35.9%) and thrombocytopenia (21.9%). TEAEs led to Rina-S dose reductions in 15.6% of pts and discontinuation of Rina-S in 3.1% of pts; 37.5% of pts had serious TEAEs. There was 1 related (assessed by investigator) grade 5 TEAE at 120 mg/m 2 confounded by comorbidities; no fatal TEAEs occurred at 100 mg/m 2 . No signals of ocular toxicity, neuropathy, or interstitial lung disease were observed. In efficacy-evaluable pts (median follow-up: 18.7 weeks), the unconfirmed ORR was 50%, including 2 complete responses, with Rina-S 100 mg/m 2 (n = 22) and 45.5% with 120 mg/m 2 (n = 33). DCR was 100% and 81.8% with 100 mg/m 2 and 120 mg/m 2 , respectively. Responses were ongoing for 9 of 11 (81.8%) and 12 of 15 (80.0%) responders with 100 mg/m 2 and 120 mg/m 2 , respectively. Conclusions: Rina-S showed encouraging anti-tumor activity in pts with heavily pretreated EC and had a manageable safety profile consistent with previous reports. Further evaluation of single-agent Rina-S in pts with advanced EC is ongoing. Clinical trial information: NCT05579366 .