Merck & Co. partner Sichuan Kelun Biotech Biopharmaceutical announced another Phase 3 success for the TROP2-targeted antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870), this time in combination with Merck’s PD-1 inhibitor Keytruda (pembrolizumab) as a first-line treatment for non-small cell lung cancer (NSCLC).
An independent data monitoring committee concluded that the combination of sac-TMT plus Keytruda met the trial’s primary endpoint by delivering a statistically significant improvement in progression-free survival (PFS), while also demonstrating a positive trend in overall survival (OS), a key secondary endpoint.
The OptiTROP-Lung05 study is a randomized, open-label, multicenter Phase 3 trial conducted in China, comparing sac-TMT plus Keytruda versus Keytruda monotherapy as first-line treatment for locally advanced or metastatic NSCLC with a tumor proportion score (TPS) ≥1%.
First ADC–checkpoint inhibitor combo success in Phase 3
According to Kelun, OptiTROP-Lung05 represents the first time globally that an ADC combined with an immune-checkpoint inhibitor has achieved success in a Phase 3 study.
Kelun intends to use the positive results to pursue what would be sac-TMT’s third approved indication in China. The ADC received its first approval in 2024 for triple-negative breast cancer (TNBC), followed by a March 2025 approval for second-line EGFR-positive NSCLC. Kelun presented the corresponding Phase 3 data for EGFR-mutant NSCLC at the ASH annual meeting this year. A supplemental filing is also under review in China seeking approval for sac-TMT in second-line hormone receptor-positive, HER2-negative breast cancer.
Merck obtained rights to develop and commercialize sac-TMT outside Greater China under a 2022 licensing deal with Kelun. However, a key question for the US market is the study’s relevance to American treatment standards: although Keytruda monotherapy is FDA-approved for first-line PD-L1–positive NSCLC, the preferred US standard of care is generally Keytruda plus platinum-based chemotherapy. The US FDA has previously highlighted such discrepancies in standards of care when reviewing China-origin PD-1 inhibitors.
Kelun currently has nine registrational Phase 3 trials underway in China for sac-TMT. Merck, meanwhile, is advancing a global program of 15 Phase 3 studies, evaluating sac-TMT both as monotherapy and in combination with Keytruda or other anticancer agents.