Sacituzumab tirumotecan (sac-TMT), a core asset of Sichuan Kelun-Biotech, is a novel TROP2-directed ADC being developed for multiple solid tumors, including NSCLC, breast, gastric, gynecologic, and genitourinary cancers. Sac-TMT is approved for marketing in lung cancer. A new indication application for sac-TMT in combination with pembrolizumab (KEYTRUDA) as first‑line treatment for locally advanced or metastatic NSCLC who have PD-L1 TPS≥1% and are EGFR-negative and anaplastic lymphoma kinase (ALK)-negative has been accepted for review by the NMPA, and has entered the priority review and approval process. As of today, Kelun-Biotech has initiated 9 registrational clinical studies in China. MSD is evaluating 17 ongoing global Phase III clinical studies of sac-TMT as a monotherapy or in combination with pembrolizumab or other anti-cancer agents for several types of cancer. These studies are sponsored and led by MSD.

In May 2022, Sichuan Kelun-Biotech licensed exclusive rights to Merck to develop and commercialize sac-TMT outside Greater China. Merck is currently evaluating sac-TMT in 15 global Phase III trials across six tumor types and secured additional development funding from Blackstone Life Sciences in 2025. 

In January 2026, sac-TMT in combination with pembrolizumab for the first-line treatment of patients with locally advanced or metastatic NSCLC who have PD-L1 TPS≥1% and are EGFR-negative and ALK-negative were granted Breakthrough Therapy Designation by the NMPA. 

At ASCO 2026, the Phase III OptiTROP-Lung05 study established sac-TMT plus pembrolizumab as a potential new frontline treatment option for PD-L1–positive advanced NSCLC, becoming the first Phase III trial to demonstrate a significant benefit for an ADC combined with an immune checkpoint inhibitor in this setting.

Key Efficacy Highlights

• Primary endpoint met: Sac-TMT plus pembrolizumab significantly improved progression-free survival (PFS) versus pembrolizumab alone. 

• Median PFS: Not reached (NR) vs. 5.7 months (HR = 0.35), representing a 65% reduction in the risk of disease progression or death. 

• 12-month PFS rate: 62.4% vs. 29.0%. 

• Objective response rate (ORR): 70.2% vs. 42.0%. 

• Deep response rate: 49.0% v.s 25.9%. 

• 12-month duration of response: 77.7% vs. 59.4%. 

• 12-month Overall survival (OS): 80.4% vs. 68.9%. 

• Consistent efficacy observed across PD-L1 TPS ≥50% and 1–49% subgroups, as well as squamous and non-squamous NSCLC populations. 

Key Safety Highlights

• Higher incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) with Sac-TMT + pembrolizumab, mainly driven by expected hematologic toxicities. 

• Pembrolizumab discontinuation rates due to TEAEs were similar between treatment arms. 

• No sac-TMT-related deaths were reported. 

• No new safety signals identified; safety profile remained consistent with the known profiles of both agents. 

• Overall safety was considered manageable, supporting the feasibility of the ADC-immunotherapy combination in the frontline setting.

KOL insights

“Results from the OptiTROP-Lung05 study support sac-TMT plus pembrolizumab as a potential new treatment option for first-line PD-L1–positive advanced NSCLC without EGFR or ALK alterations.” –Expert Opinion

“TEAEs led to discontinuation of Sac-TMT or pembrolizumab for 3.8% and 5.3% of those in the combination, and discontinuation of pembrolizumab for 4.9% of those in the control arm. They resulted in death for 5 patients (2.4%) in the combination arm vs 13 (6.4%) in the control arm. No treatment-related deaths were attributed to sac-TMT.”–Expert Opinion

Conclusion

NSCLC accounts for approximately 80–85% of all lung cancer cases, highlighting the substantial need for improved frontline therapies. In the Phase III OptiTROP-Lung05 study, sac-TMT plus pembrolizumab significantly improved progression-free survival and demonstrated a favorable overall survival trend versus pembrolizumab alone in patients with PD-L1–positive advanced NSCLC without targetable genomic alterations. As the first Phase III trial to demonstrate the benefit of an ADC combined with an immune checkpoint inhibitor in the first-line NSCLC setting, the findings position the "ADC+IO" approach as a promising new treatment paradigm. 

While sac-TMT is generating strong clinical momentum across multiple tumor types and combinations, the key strategic issue is that Merck has not yet designed a definitive Phase III trial for the PD-L1–low/negative nonsquamous first-line NSCLC setting. This creates a potential “missing segment” in its lung cancer development plan. Merck is aware of this gap but is still evaluating the optimal approach—balancing efficacy, toxicity, and how best to position sac-TMT alongside Keytruda and emerging combinations—so no final development decision has yet been confirmed.