Sacituzumab tirumotecan versus treatment of physician's choice in previously treated endometrial cancer (TroFuse-005/ENGOT-en23/GOG-3095): a randomised, open-label, phase 3 trial.

Patients with advanced or recurrent endometrial cancer who progress after platinum-based chemotherapy and immunotherapy have limited treatment options and poor prognosis, which motivated this study. The trial is registered on ClinicalTrials.gov as NCT06132958 (MK-2870-005), a phase 3, randomized, active-controlled study sponsored by Merck Sharp & Dohme, started December 6, 2023, with a planned enrollment of 710 in the registry . Doxorubicin, one of the control agents, is an anthracycline topoisomerase inhibitor whose cardiotoxicity (cardiomyopathy risk of about 11% at cumulative doses of 450–550 mg/m²) is flagged in a boxed warning, partly explaining the tolerability limits of later-line chemotherapy [Regulatory document·C].

TroFuse-005/ENGOT-en23/GOG-3095 is a randomized, open-label phase 3 trial across 242 gynaecological oncology centres in 31 countries and regions. It enrolled women aged 18 or older with histologically confirmed advanced or recurrent endometrial carcinoma or carcinosarcoma who had received up to three previous lines of therapy, including platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. 776 patients were randomized 1:1 to sac-TMT (4 mg/kg IV on days 1 and 15 of each 28-day cycle) or treatment of physician's choice (doxorubicin 60 mg/m² every 3 weeks, or paclitaxel 80 mg/m² on days 1, 8, and 15 of each 28-day cycle). At median follow-up of 14.0 months, median PFS by BICR was 7.2 months (95% CI 5.6–7.6) with sac-TMT versus 3.9 months (3.7–5.3) with TPC (HR 0.59 [95% CI 0.50–0.70]; p<0.0001); median OS was 19.0 months (16.1–not reached) versus 12.1 months (11.0–15.2) (HR 0.68 [0.55–0.84]; p=0.0001). Grade ≥3 adverse events occurred in 69% (265/384) of the sac-TMT group versus 57% (210/367) of the TPC group; serious adverse events in 35% versus 32%; treatment-related deaths in 3 (<1%) patients in each group. Mechanistically, the paper states that sac-TMT is a TROP2-directed antibody-drug conjugate with a unique bifunctional linker that maximises delivery of a belotecan-derived topoisomerase I inhibitor payload to tumour cells [Peer-reviewed·L].

These results advance the ongoing registry-listed study to a stage where both dual primary endpoints (PFS by BICR and OS) met statistical significance, with PFS and OS prespecified as dual primary endpoints under a multiple-testing approach . The investigators conclude the findings support sac-TMT as a new standard of care for endometrial cancer after chemotherapy and immunotherapy. Notably, actual enrollment of 776 exceeded the registry's planned 710 .

Undisclosed information includes detailed efficacy by subgroup (e.g., mismatch repair status, TROP2 expression level), objective response rates, subsequent therapy distribution, and quality-of-life outcomes; regulatory submission plans and timelines were also not disclosed. The trial remains ongoing in the registry (primary completion date January 10, 2028), with longer-term follow-up data pending . This article does not constitute investment advice (needs verification).