Merck’s sacituzumab tirumotecan improves survival vs chemotherapy in advanced/recurrent endometrial cancer
- At median follow‑up 14.0 months, sac‑TMT reduced risk of death by 32% (HR 0.68), extending median OS to 19.0 vs 12.1 months (gain 6.9 months).
- Sac‑TMT reduced risk of disease progression or death by 41% (HR 0.59), extending median PFS to 7.2 vs 3.9 months (gain 3.3 months).
- Objective response rate was 35.1% vs 17.3% (difference 17.8%); median duration of response was 11.1 vs 6.9 months for sac‑TMT vs chemotherapy.
- The FDA has accepted a BLA for priority review with a PDUFA target action date of June 15, 2027; TroFuse‑005 enrolled 776 patients.
Key results
At a pre‑specified interim analysis (median follow‑up 14.0 months), sacituzumab tirumotecan (sac‑TMT) met both dual primary endpoints in TroFuse‑005. Sac‑TMT reduced the risk of death by 32% (HR 0.68; 95% CI 0.55–0.84; P<0.0001), extending median overall survival to 19.0 months versus 12.1 months with treatment of physician’s choice (TPC). Sac‑TMT reduced the risk of disease progression or death by 41% (HR 0.59; 95% CI 0.50–0.70; P<0.0001), extending median progression‑free survival to 7.2 months versus 3.9 months. Objective response rate was 35.1% versus 17.3% (difference 17.8%; P<0.00001), with median duration of response 11.1 versus 6.9 months.
Safety
Treatment‑related adverse events (TRAEs) of any grade occurred in 97.1% of sac‑TMT patients and 89.6% of TPC patients. Grade ≥3 TRAEs were reported in 54.4% versus 41.4%. The most common Grade ≥3 events with sac‑TMT were anemia (23.7%), neutropenia (20.1%) and oral mucositis/stomatitis (9.9%). Treatment discontinuation rates were low (3.1% sac‑TMT; 4.9% TPC), and TRAEs led to death in 0.8% (N=3) in each arm. Health‑related quality of life was maintained over time with sac‑TMT.
Regulatory and dissemination
TroFuse‑005 data were presented in a Presidential Symposium at the ESMO Congress 2026 and published concurrently in The Lancet. Based on these data, the U.S. FDA has accepted a Biologics License Application for priority review for sac‑TMT in the indicated patient population, with a PDUFA target action date of June 15, 2027.
Trial design and development program
TroFuse‑005 is a randomized, open‑label, global Phase 3 trial (NCT06132958) that enrolled 776 patients with advanced or recurrent endometrial carcinoma previously treated with platinum‑based chemotherapy and anti‑PD‑1/PD‑L1 therapy. Patients were randomized to sac‑TMT (4 mg/kg, Day 1 every two weeks) versus physician’s choice chemotherapy (doxorubicin or paclitaxel) and assessed for OS and PFS by blinded independent central review; ORR was a key secondary endpoint. Sac‑TMT is being evaluated across an 18‑trial global Phase 3 TroFuse program.
Source: Merck