Interim overall survival data on a TROP2 ADC from Merck and Chinese partner Kelun-Biotech provide support for the pharma’s big bet on its potential to help navigate Keytruda’s impending loss of exclusivity.
Phase 3 data for Merck’s Kelun-Biotech-partnered TROP2-directed antibody-drug conjugate have boosted analyst expectations for a key pillar of the company’s post-Keytruda strategy.
Merck has ceded a head start in the TROP2 space, with Gilead Sciences winning FDA approval for Trodelvy in 2020 and AstraZeneca and Daiichi Sankyo bringing Datroway to market in 2025. But data presented over the weekend at the American Society for Clinical Oncology (ASCO) annual meeting suggest Merck’s candidate, sacituzumab tirumotecan (sac-TMT), could set itself apart in a first-line setting, which Gilead and AstraZeneca are still chasing with their antibody-drug conjugates (ADCs).
Having shared some data ahead of the event, China-based Kelun provided overall survival (OS) results in its full presentation of a late-phase readout. The data come from a Phase 3 trial that studied sac-TMT as a first-line treatment for non-small cell lung cancer (NSCLC) in Chinese patients.
After 12 months, the OS rate in patients who received sac-TMT plus Merck’s blockbuster checkpoint inhibitor Keytruda was 80.4%. The 12-month OS rate was 68.9% in the Keytruda monotherapy arm. Sac-TMT plus Keytruda “demonstrated a clear advantage” over single-agent checkpoint inhibitor therapy, BMO Capital Markets said in a note to investors on Friday.
Median OS on Keytruda monotherapy “appears slightly lower than what would be expected from a global study at 14.5 months,” the analysts said. Yet they still view “the clear separation” from monotherapy “as supportive of broader expected efficacy from the agent as Merck transitions to global studies.”
The ASCO presentation also expanded on the progression-free survival (PFS) data that Kelun reported in an abstract ahead of the meeting. The abstract revealed sac-TMT cut the risk of tumor progression by 65%. Kelun’s presentation showed the result was consistent across blinded independent central review (BICR) and investigator-assessed PFS. These analyses yielded hazard ratios—a marker of the risk of death during the trial—of 0.35 and 0.38, respectively. A lower hazard ratio means better survival.
Trodelvy and Datroway have yet to come to market in first-line NSCLC, though their developers are targeting the indication. Gilead expects to provide an update on a Phase 3 trial of Trodelvy in the setting this year. Phase 3 data on AstraZeneca and Daiichi’s Datroway in first-line NSCLC are also due this year.
Merck’s global Phase 3 trial in first-line NSCLC has an estimated primary completion of January 2028. But while Merck could be third to market in the indication in the U.S., BMO analysts see signs sac-TMT may have an edge over the competition.
“While investors have started to acknowledge the potentially differentiated efficacy of sac-TMT across tumor types, today’s results likely reinforce this, demonstrating clear consistency in PFS endpoints across BICR and investigator assessed measures with more promising overall survival analysis,” they said.
Developments outside the TROP2 space offered further encouragement. After seeing data on Akeso and Summit Therapeutics’ VEGF/PD-1 therapy, BMO analysts said they were “incrementally more confident about Merck’s long-term opportunity to both defend its position in NSCLC and even expand with sac-TMT.”
