Merck takes on the TROP2 leaders again in breast cancer

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

Note: *includes NSCLC driven by mutations in ALK, ROS1, BRAF, NTRK, MET or RET. Source: OncologyPipeline & clinicaltrials.gov.