As a cornerstone of Merck & Co.’s post-Keytruda oncology strategy, sac-TMT has cleared a clinical milestone. In its first global phase 3 win, the TROP2 antibody-drug conjugate delivered results that are “pretty consistent” with earlier China data, according to Marjorie Green, M.D., Merck’s head of oncology clinical development.
Sac-TMT, partnered with China’s Kelun-Biotech, reduced the risk of death by 32%—and the risk of disease progression or death by 41%—compared with chemotherapy in patients with previously treated endometrial cancer. The patients had received prior treatment with platinum-base chemo and PD-(L)1 inhibitor therapy.
Derived from the TroFuse-005 trial and presented at the European Society for Medical Oncology 2026 Congress, the data gave sac-TMT its first positive global phase 3 report out of 18 trials that Merck has launched in one of the industry’s broadest clinical development programs for a single drug.
Based on the positive data, the FDA has accepted Merck’s application for a sac-TMT approval in previously treated endometrial cancer with a target action date of June 15, 2027. For sac-TMT, Merck also earned an FDA Commissioner’s National Priority Voucher (CNPV), which is expected to further accelerate the agency’s review.
Merck is posting the landmark win amid lingering questions about the translatability of Chinese clinical data to a global population. Seventeen of Merck’s phase 3 trials for sac-TMT were launched before TroFuse-005 read out, mostly backed by data from China.
In TroFuse-005, Merck saw “pretty consistent” data compared with China, Green said during an interview with Fierce.
In the endometrial cohort of a phase 1/2 trial with patients primarily from China, sac-TMT previously recorded an objective response rate of 36.9% and a median progression-free survival of 5.6 months at the 4 mg/kg dose used in TroFuse-005, and a 36.4% ORR and 7.3-month PFS for the 5 mg/kg group.
Now, in TroFuse-005, sac-TMT extended median PFS by 3.3 months to 7.2 months compared with chemo. The ADC also doubled the ORR rate to 35.1%. Patients in the global phase 3 were less heavily pretreated than the early-phase trial.
As to overall survival, sac-TMT extended median OS by 6.9 months compared with chemo, reaching 19 months in TroFuse-005.
The TroFuse-005 trial likely won’t put the China-to-global question to rest. Just a few weeks ago, detailed data from a failed global phase 3 study of Gilead Sciences’ rival TROP2 ADC Trodelvy in first-line non-small cell lung cancer showed notably better results from China than in the Western population.
To Green, the hope is that sac-TMT will continue to shine across 10 phase 3 trials in women’s cancers, including the TroFuse-033 trial testing the ADC as a first-line therapy for mismatch repair proficient (pMMR) endometrial cancer.
“For those physicians who treat endometrial, cervical cancer, ovarian cancer, this is hopefully the first of many readouts that will show the potential of a therapy that can clinically meaningfully improve outcomes and be tolerable for patients,” Green said.
On that last point, Green pointed to sac-TMT’s ability to keep patients on treatment and have a long duration of response (DoR). In TroFuse-005, patients’ median DoR reached 11.1 months for sac-TMT, versus 6.9 months in the control arm. Also at ESMO 2026, Kelun detailed a China phase 3 win for sac-TMT in first-line, PD-L1-negative non-small cell lung cancer. In that trial, sac-TMT and Keytruda doubled the median DoR versus chemo and Keytruda to 13.6 months.
“That’s what makes me excited about the global potential and ability to be able to do well in phase 3 studies,” Green said.
To further highlight sac-TMT’s tolerability profile as a contributor to its treatment effect, Green pointed to how overall discontinuations due to adverse events was numerically higher in the control arm of TroFuse-005, even though the average duration of therapy in the control arm was about 15 weeks, compared to more than 30 weeks with sac-TMT.
With projected worldwide sales of $1.5 billion in 2033, gynecological tumors together account for 16% of Leerink Partners analysts’ sac-TMT peak sales estimates, according to an Oct. 21 note.
Also in endometrial cancer, Merck at ESMO 2026 detailed positive results from the phase 3 Keynote-C93 trial for Keytruda monotherapy in first-line mismatch repair deficient (dMMR) endometrial cancer. Patients had not previously received systemic chemotherapy but may have experienced recurrence after receiving prior adjuvant therapy for early-stage disease.
The study showed that Keytruda reduced the risk of progression or death by 43% versus platinum doublet chemo, extending median PFS to 38.2 months, versus 8.4 months for chemo.
A favorable trend toward a 23% OS improvement was observed as the trial continues its OS follow-up.
Before the latest readout, Keytruda plus chemo already earned a broad FDA label in first-line endometrial cancer covering both dMMR and pMMR tumors. In the dMMR cohort, the Keytruda-chemo combo posted a 70% PFS advantage over chemo.
“I think right now people are leaning more towards chemotherapy, but not everyone can take it,” Green said. For those patients, Keytruda monotherapy could offer another option, she said.