Merck matches Kelun’s saci-tirumo efforts

Months after taking the anti-TROP2ADC sacituzumab tirumotecan into pivotal development in relapsed lung cancer Merck & Co is starting a new phase 3 study in a similar setting, as well as embarking on pivotal development in advanced HER2-negative breast cancer, an approved use for Gilead's rival Trodelvy, and adjuvant NSCLC.

The three new trials are to start enrolling shortly, and appeared on the clinicaltrials.gov registry within three days of each other last week. The metastatic NSCLC study will test saci-tirumo in EGFR-mutant non-squamous patients who have already received targeted anti-EGFR therapy, and both this and the breast cancer test broadly mirror pivotal development already started by Kelun in Asia.

In May 2022 Merck paid Kelun $47m for undisclosed ADC projects later revealed to include saci-tirumo. The tally of disclosed phase 3 trials now comprises four sponsored by Kelun (a first-line triple-negative breast cancer study kicked off last month) and six run by Merck.

Compare and contrast

The NSCLC trial Merck begun in November included the same EGFR-mutant setting as the just-revealed second-line study, but it additionally allowed other genetic mutations like ALK, ROS1 and BRAF, and had a slightly different chemo comparator option. The latest test is virtually identical to the China-focused study Kelun started earlier, except for a different allocation of survival endpoints.

In ER-positive HER2-negative breast cancer the Merck and Kelun phase 3 trials involve similar second-line or later settings, with PFS as sole primary endpoint, though the Kelun study mentions only prior chemo, whereas the Merck one mandates prior endocrine and CDK4/6 inhibitor therapy. The other big difference is that Merck’s trial includes a Keytruda combo.

The somewhat undemanding benchmark Trodelvy set in HER2-negative breast cancer was 5.5 months of median PFS in the Tropics-02 study, though later AstraZeneca/Daiichi Sankyo’s anti-TROP2 ADC rival datopotamab deruxtecan scored 6.9 months in Tropion-Breast01 (the chemo comparator might be expected to yield 4-5 months, according to these two studies).

And the phase 3 adjuvant NSCLC trial appears to be a new departure for a TROP2-directed ADC. This too will involve a combo with Keytruda, and compare against Keytruda alone, in stage II to IIIB disease in the slightly unusual setting of patients who already received neoadjuvant Keytruda plus chemo before having their tumours resected, but who didn’t achieve pathological complete response.

Though Merck has made a separate push into ADCs through last October’s $5.5bn deal with Daiichi Sankyo, the latest efforts suggests that it’s not about to take its foot off the gas with the Kelun tie-up any time soon. 

Pivotal trials of sacituzumab tirumotecan

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

This is an updated version of a story published earlier.