Kelun-Biotech's sac-TMT meets Phase III endpoint in first-line PD-L1-negative NSCLC

Sichuan Kelun-Biotech Biopharmaceutical (HKEX: 6990.HK) has reported that its Phase III OptiTROP-Lung06 trial of sacituzumab tirumotecan (sac-TMT, also known as SKB264/MK-2870) plus Merck's Keytruda (pembrolizumab) met its primary endpoint of progression-free survival in first-line PD-L1-negative non-squamous non-small cell lung cancer — a population where immunotherapy alone offers limited benefit and platinum-based chemotherapy remains the backbone of treatment.

The result extends the clinical case for sac-TMT beyond PD-L1-positive disease. In the companion OptiTROP-Lung05 study, sac-TMT plus pembrolizumab previously demonstrated superiority over pembrolizumab monotherapy in PD-L1-positive NSCLC, with those findings presented at ASCO 2026 and published in The Lancet. Together, the two trials position sac-TMT as a potential first-line option across the full spectrum of PD-L1 expression in driver gene-negative non-squamous NSCLC. The findings also strengthen the clinical foundation for Merck's global development program for sac-TMT, which the company licensed outside Greater China in 2022.

Sac-TMT is a TROP2-directed antibody-drug conjugate that delivers a belotecan-derived topoisomerase I inhibitor payload intracellularly, inducing DNA damage and apoptosis in tumor cells while enabling bystander killing of adjacent cells through membrane-permeable payload release. The combination with pembrolizumab, which blocks the PD-1 checkpoint to restore T-cell-mediated tumor killing, is designed to exploit synergistic immune and cytotoxic mechanisms — potentially overcoming the limited immunotherapy response seen in PD-L1-low or -negative tumors.

OptiTROP-Lung06 is a randomized, open-label, multicenter Phase III trial comparing sac-TMT plus pembrolizumab against pembrolizumab plus pemetrexed and platinum-based chemotherapy. At a pre-specified interim analysis, the combination demonstrated a statistically significant and clinically meaningful PFS improvement, with a positive OS trend also observed. The safety profile was consistent with prior studies, with no new signals identified. Specific numerical data — median PFS, hazard ratios, and p-values — were not disclosed in the announcement.

Kelun-Biotech plans to engage China's Center for Drug Evaluation based on these results. Sac-TMT already holds four approved indications in China, including previously treated EGFR-mutant non-squamous NSCLC and triple-negative breast cancer, and is the world's first TROP2-directed ADC approved for lung cancer. A new indication application for first-line PD-L1-positive NSCLC based on the Lung05 study is under priority review at China's NMPA. The Lung06 results could support an additional regulatory submission seeking to expand use into the PD-L1-negative first-line setting. Merck holds exclusive rights to develop and commercialize sac-TMT outside Greater China and has 17 ongoing global Phase III studies evaluating the molecule.

The PD-L1-negative first-line setting is currently treated with pembrolizumab plus pemetrexed and platinum chemotherapy — the regimen against which Lung06 was evaluated — alongside atezolizumab-based regimens and dual checkpoint combinations such as nivolumab plus ipilimumab. These approaches rely on chemotherapy or dual immunotherapy to achieve meaningful benefit in this population. If confirmed in full data presentation, an ADC-plus-checkpoint regimen capable of replacing cytotoxic chemotherapy could represent a meaningful shift in first-line treatment, although cross-trial comparisons remain limited until detailed results are presented and peer-reviewed.

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