Sacituzumab tirumotecan plus pembrolizumab improves PFS in PD-L1-negative NSCLC

Kelun-Biotech announced at the 2026 ESMO Congress in Madrid that the Phase III OptiTROP-Lung06 trial of sacituzumab tirumotecan (sac-TMT, also known as SKB264/MK-2870) plus pembrolizumab met its primary endpoint of progression-free survival in first-line treatment of non-squamous non-small cell lung cancer with PD-L1 tumor proportion score below 1% and without EGFR or ALK alterations, according to a company press release issued 25 October. The company said Professor Caicun Zhou of Shanghai East Hospital, Tongji University presented the findings as late-breaking abstract LBA66, and the study was published concurrently in The New England Journal of Medicine.

The open-label, randomized, multicenter trial enrolled 455 patients and randomly assigned them to sac-TMT plus pembrolizumab or to platinum-based doublet chemotherapy with pemetrexed plus cisplatin or carboplatin, also combined with pembrolizumab. Blinded independent central review assessed progression-free survival, and overall survival was a secondary endpoint. At the June 9, 2026 data cutoff, with median follow-up of 9.7 months, blinded independent central review showed patients in the sac-TMT arm reached a median progression-free survival of 15.0 months (95% CI 9.9 to not estimable), compared with 5.7 months (95% CI 5.5 to 7.4) in the chemotherapy arm, yielding a hazard ratio of 0.49 (95% CI 0.36 to 0.65, P<0.0001).

By blinded independent central review, the objective response rate was 50.2% in the sac-TMT plus pembrolizumab arm and 47.3% in the chemotherapy plus pembrolizumab arm. Median duration of response was 13.6 months versus 6.8 months (hazard ratio 0.47, 95% CI 0.29 to 0.77). Deep response, meaning a complete or partial response accompanied by a reduction of at least 50% in the sum of target lesion diameters, occurred in 28.8% of patients in the sac-TMT arm versus 17.3% in the chemotherapy arm. Overall survival showed a trend favoring sac-TMT, with a hazard ratio of 0.58 (95% CI 0.38 to 0.88), but median overall survival was not reached in either group at this interim analysis.

Safety was generally consistent with the known profiles of the individual agents, and no new safety signals were seen, Kelun-Biotech said. The sac-TMT combination had lower rates of grade 3 or higher treatment-emergent adverse events and of adverse events leading to dose reduction or permanent discontinuation than the chemotherapy combination, while the incidence of interstitial lung disease/pneumonitis was similar.

Professor Zhou said in the press release that the results add to the clinical value of the regimen and, together with OptiTROP-Lung05 presented at ASCO 2026, provide Phase III evidence of improved progression-free survival in NSCLC that lacks actionable genomic alterations, regardless of PD-L1 status. Kelun-Biotech describes OptiTROP-Lung06 as the first Phase III study of an antibody-drug conjugate paired with an immune checkpoint inhibitor to reach its primary endpoint as initial treatment for non-squamous NSCLC that is driver-gene negative and PD-L1 negative.

Sac-TMT is a TROP2-directed antibody-drug conjugate with a belotecan-derivative topoisomerase I inhibitor payload and a drug-to-antibody ratio of 7.4, according to the company. MSD, the tradename of Merck & Co., Inc., holds rights to develop and commercialize sac-TMT outside Greater China and has initiated 18 global Phase III studies of the drug alone or in combination.