Merck·Kelun, sac-TMT+pembrolizumab NSCLC PD-L1 ≥50% Phase 3 Enrollment
Clinical Overview: Strategic Design of TroFuse-007
TroFuse-007 (NCT06170788) is a Phase 3, randomized, open-label clinical trial conducted by Merck Sharp & Dohme (MSD) in collaboration with Sichuan Kelun-Biotech (6990.HK), initiated in December 2023. The target patient population consists of patients with metastatic non-small cell lung cancer (NSCLC) receiving first-line treatment with a PD-L1 tumor proportion score (TPS) ≥50%, with a total of 614 patients to be enrolled. The treatment groups will directly compare sacituzumab tirumotecan (sac-TMT / MK-2870 / SKB264) plus pembrolizumab (Keytruda) versus pembrolizumab alone. The primary endpoint is overall survival (OS), with an expected primary completion date of January 2028 and a final completion date of May 2030.
Mechanism of Action: Complementary Dual Action of TROP2 ADC + PD-1 Inhibitor
sac-TMT is an antibody-drug conjugate (ADC) targeting TROP2 (trophoblast cell-surface antigen 2). TROP2 is a tumor-associated antigen overexpressed in various solid tumors, including NSCLC. sac-TMT selectively delivers a hydrolyzable cleavable linker-conjugated belotecan analog cytotoxic payload (KL610023) into cancer cells. The PD-1 inhibitor, pembrolizumab, releases immune exhaustion and activates T-cell responses. The core hypothesis is the dual mechanism of sac-TMT directly adding cytotoxic effects. The PD-L1 ≥50% group is a biomarker-enriched patient population with intrinsically high responsiveness to immune checkpoint inhibitors, and the addition of ADC is expected to create a strong synergistic effect.
Prior Data: Unprecedented Phase 3 Signal from OptiTROP-Lung05
The Phase 3 OptiTROP-Lung05 trial, which evaluated the same drug combination (sac-TMT+pembrolizumab) in 413 patients with PD-L1 TPS ≥1% NSCLC, presented its results at the 2026 ASCO Annual Meeting (Abstract #8506) and was simultaneously published in The Lancet. The median progression-free survival (mPFS) in the combination arm was not reached (NR), compared to 5.7 months in the single-agent arm, representing a 65% reduction in the risk of progression (HR 0.35; 95% CI 0.26-0.47; p<0.0001), and the objective response rate (ORR) was 70.2% versus 42.0%. The overall survival (OS) HR was also 0.55 (95% CI 0.36-0.85), showing positive signals, and the safety profile was consistent with the existing profiles of each single agent. Because TroFuse-007 selects an even narrower and more immune-responsive patient population (PD-L1 ≥50%), a stronger effect size is expected compared to OptiTROP-Lung05.
Market Landscape: Potential for Regime Change in Keytruda Monotherapy as Standard of Care
In first-line treatment of PD-L1 TPS ≥50% NSCLC, pembrolizumab (Keytruda) monotherapy, based on the KEYNOTE-024 study, is the global standard of care. Keytruda's total revenue in 2025 is $31.6 billion, and NSCLC is one of its key indications. Competing drugs include cemiplimab (Libtayo) from Sanofi·Regeneron, which has captured some market share with EMPOWER-Lung 1 data, but it lags significantly behind Keytruda in market share. If ADC combination therapy demonstrates improved OS in this patient population, a regime change from monotherapy to combination therapy could become a reality, further strengthening MSD's market position.
Partnership Structure and Regulatory Pathway
MSD acquired exclusive global development, manufacturing, and commercialization rights for sac-TMT from Kelun-Biotech in May 2022, excluding Greater China. Kelun-Biotech, a Hong Kong-listed company (6990.HK), retains rights to the Greater China market. TroFuse-007 is a global pivotal trial enrolling patients in more than 30 countries and over 174 clinical sites. Positive results are likely to lead to simultaneous FDA and EMA submissions, and it could become a key pathway for entry into the global first-line NSCLC market.
TroFuse-007 (NCT06170788) is a pivotal trial directly comparing sacituzumab tirumotecan plus pembrolizumab to the current global standard of pembrolizumab monotherapy in first-line PD-L1 TPS ≥50% NSCLC, with the aim of demonstrating superior OS. The same drug combination was previously evaluated in the PD-L1 ≥1% population in OptiTROP-Lung05, which showed impressive results, including a PFS HR of 0.35 (p<0.0001) and an ORR of 70.2%, as presented at the 2026 ASCO meeting and published in The Lancet. Given that the TroFuse-007 patient population (PD-L1 ≥50%) has higher immune responsiveness, the effect size is likely to be even greater than in OptiTROP-Lung05. If the ADC combination therapy replaces the $31.6 billion Keytruda monotherapy standard of care in 2025, both MSD (MRK) and Kelun-Biotech (6990.HK) can expect significant revenue growth. Competition with AstraZeneca·Daiichi Sankyo's datopotamab deruxtecan (Dato-DXd, TROPION-Lung series) in the same TROP2 ADC space is expected to intensify, and the primary OS data release for TroFuse-007, expected in early 2028, will be a key monitoring point for long-term investment.
Source: ClinicalTrials.gov (api_ct)