Kelun-Biotech (6990.HK) is presenting Phase III data at ASCO 2026 showing that sacituzumab tirumotecan (sac-TMT, MK-2870, or SKB264) combined with Merck's Keytruda (pembrolizumab) cut the risk of progression or death by 65% compared with pembrolizumab alone in first-line PD-L1-positive advanced NSCLC. Kelun also reported a separate pivotal Phase II readout for its RET inhibitor lunbotinib fumarate, which showed response rates above 80% in both treatment-naïve and pre-treated patients with RET fusion-positive disease.
The OptiTROP-Lung05 study enrolled 413 patients with previously untreated locally advanced or metastatic NSCLC without EGFR or ALK alterations and PD-L1 tumor proportion score of at least 1%, covering both squamous and non-squamous histologies. Patients were randomized 1:1 to sacituzumab tirumotecan at 4 mg/kg every two weeks plus pembrolizumab at 400 mg every six weeks, or pembrolizumab monotherapy. At a median follow-up of 10.5 months, median progression-free survival by blinded independent central review was not reached in the combination arm versus 5.7 months with pembrolizumab alone (HR 0.35; 95% CI 0.26–0.47; p < 0.0001). The objective response rate was 70.2% in the combination group versus 42.0% with pembrolizumab monotherapy. Overall survival data remain immature but trended in favor of the combination (HR 0.55; 95% CI 0.36–0.85). The PFS benefit was consistent across PD-L1 subgroups, with hazard ratios of 0.28 and 0.47 for TPS 1–49% and TPS ≥ 50% populations respectively, and held across both squamous (HR 0.44) and non-squamous (HR 0.28) histologies. Grade 3 or higher treatment-emergent adverse events occurred in 55.3% of patients in the combination arm versus 31.4% with pembrolizumab alone, though treatment discontinuation rates were low: 3.8% discontinued sacituzumab tirumotecan and 5.3% discontinued pembrolizumab in the combination arm, comparable to the 4.9% discontinuation rate in the monotherapy group. China's National Medical Products Administration has accepted a supplemental new drug application for the combination and placed it on priority review.
The lunbotinib fumarate pivotal study enrolled 163 patients across two cohorts — 71 who had received prior platinum-based chemotherapy and immunotherapy, and 92 who were treatment-naïve — all with advanced RET fusion-positive NSCLC. At data cutoff with median follow-up exceeding 20 months in both cohorts, independent review committee-confirmed response rates were 87.1% (95% CI 77.0–93.9) in pre-treated patients and 81.3% (95% CI 71.8–88.7) in treatment-naïve patients. Median PFS reached 27.5 months in pre-treated patients, while the treatment-naïve cohort had not yet reached median PFS at 24 months, with 24-month PFS rates of 52.1% and 59.9% respectively. Median OS was not reached in either group, with 24-month OS rates of 65.7% and 74.1%. Among patients with baseline brain metastases, ORR was 82.6% in the pre-treated cohort and 75.0% in treatment-naïve patients, with six complete intracranial responses in each group. Grade 3 or higher treatment-related adverse events occurred in 40.5% of patients overall; only two patients (1.2%) permanently discontinued treatment, and no fatal treatment-related adverse events were reported. The NMPA has accepted a new drug application for lunbotinib fumarate for RET fusion-positive locally advanced or metastatic NSCLC.
Competitive context
Sacituzumab tirumotecan is a TROP2-directed ADC that uses a bifunctional linker to deliver a belotecan-derivative topoisomerase I inhibitor payload with a drug-to-antibody ratio of 7.4, and the OptiTROP-Lung05 data represent the first Phase III evidence of an ADC-plus-checkpoint inhibitor combination outperforming checkpoint inhibitor monotherapy in first-line PD-L1-positive advanced NSCLC. Pembrolizumab monotherapy remains the established standard for this population, and while cross-trial comparisons are limited, the magnitude of the PFS hazard ratio in OptiTROP-Lung05 is numerically larger than what has been observed with chemo-IO combinations in overlapping populations. Gilead's Trodelvy (sacituzumab govitecan), the other approved TROP2 ADC, carries an SN-38 payload and holds approvals in breast cancer but has not demonstrated registrational-level data in first-line NSCLC in combination with checkpoint inhibition. Outside of Greater China, Merck holds the exclusive rights to develop and commercialize sacituzumab tirumotecan and is currently running 17 global Phase III studies of the agent.