
Merck takes on the TROP2 leaders again in breast cancer
The company is starting a phase 3 trial of sacituzumab tirumotecan in first-line TNBC.
The company is starting a phase 3 trial of sacituzumab tirumotecan in first-line TNBC.

Merck & Co has just added to the huge programme for its Kelun-originated TROP2-targeting ADC, sacituzumab tirumotecan, with another new pivotal study, this time in first-line triple-negative breast cancer.
The TroFuse-011 trial, which seeks to enrol 1,000 patients, could pit saci-T against the two approved TROP2 ADCs, Gilead’s Trodelvy and AstraZeneca/Daiichi Sankyo’s Datroway. The study, just unveiled on clinicaltrials.com, is Merck’s 12th phase 3, taking its total target patient population to nearly 10,000 – without even counting the Asian focused trials being carried out by Kelun.
Early TNBC has been transformed by Keytruda, which is approved front line in patients whose tumours express PD-L1 at ≥10%, as well as in the perioperative setting as part of a chemo combo.
Gilead’s Trodelvy is approved in late-line TNBC, while saci-T recently got a green light here in China.
TNBC delays
Trodelvy and Datroway are also being tested in front-line TNBC, in the Ascent-03 and Tropion-Breast02 trials respectively. Results from both studies had been expected last year, but have now been delayed until the first half of 2025; the imminent readouts could therefore set the bar for saci-T.
However, there are differences. For example, TroFuse-011 mandates PD-L1 expression below 10%, while Ascent-03 and Tropion-Breast02 have broader inclusion criteria, enrolling patients with PD-L1 <10%, as well as PD-L1-positive subjects who received (neo)adjuvant Keytruda, and those with comorbidities preventing checkpoint inhibitors. Tropion-Breast02 also allows PD-L1-positive patients in countries where Keytruda isn’t available.
Ascent-03 and Tropion-Breast02 are testing TROP2 ADC monotherapy versus physician’s choice of chemo, while TroFuse-011 will evaluate saci-T, with or without Keytruda, versus physician’s choice.
Another clash could come in adjuvant TNBC, where all three assets are being evaluated: saci-T in the TroFuse-012 trial; Trodelvy in Ascent-05; and Datroway in Tropion-Breast-03.
As for relapsed ER-positive, HER2-negative breast cancer, Merck is lagging behind. Datroway recently got the go ahead here, following Trodelvy’s 2023 approval, while the TroFuse-010 trial of saci-T is due to complete in 2027.
Being late to the party doesn’t seem to have deterred Merck, which earlier this month began a phase 3 trial of saci-T in ovarian cancer, joining studies in NSCLC, endometrial and cervical cancers, among others. Kelun also has various Chinese trials ongoing including SKB264-III-11, in first-line TNBC, which is due to complete next year.
Merck-sponsored sacituzumab tirumotecan phase 3 trials
Trial | Setting | Design | N | Primary completion |
---|---|---|---|---|
TroFuse-004 | 2L+ EGFR+ve & other genetically altered* non-squamous NSCLC | Vs pemetrexed or docetaxel | 556 | May 2027 |
TroFuse-005 | 2L endometrial cancer | Vs chemo | 710 | Jan 2028 |
TroFuse-007 | 1L PD-L1 ≥50% NSCLC | Keytruda combo, vs Keytruda | 614 | Jan 2028 |
TroFuse-009 | 2L+ (post EGFR TKIs) EGFR+ve non-squamous NSCLC | Vs pemetrexed + carboplatin | 520 | Sep 2028 |
TroFuse-010 | 2L+ ER+ve HER2-ve breast cancer | +/- Keytruda, vs physician’s choice | 1,200 | Jul 2027 |
TroFuse-011 | 1L PD-L1 <10% TNBC | +/- Keytruda, vs physician’s choice | 1,000 | May 2030 |
TroFuse-012 | Adjuvant TNBC | Keytruda combo, vs Keytruda +/- chemo | 1,530 | Dec 2030 |
TroFuse-015 | 3L+ gastroesophageal adenocarcinoma | Vs physician’s choice | 450 | Jan 2027 |
TroFuse-019 | Adjuvant stage II-IIIB NSCLC | Keytruda combo, vs Keytruda | 780 | Feb 2034 |
TroFuse-020 | 2L cervical cancer | Vs physician’s choice | 686 | Oct 2028 |
TroFuse-022 | 2L maintenance in platinum-sensitive ovarian cancer | +/- Avastin, vs Avastin | 770 | Apr 2030 |
TroFuse-023 | 1L maintenance in squamous NSCLC | Keytruda/chemo combo, vs Keytruda | 851 | Jan 2029 |
Note: *includes NSCLC driven by mutations in ALK, ROS1, BRAF, NTRK, MET or RET. Source: OncologyPipeline & clinicaltrials.gov.
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