Sac-TMT+Keytruda Beats Chemo in PD-L1-Negative NSCLC

Kelun-Biotech (6990.HK) announced on July 14, 2026 that the Phase 3 OptiTROP-Lung06 trial of sacituzumab tirumotecan (sac-TMT, also known as MK-2870) in combination with Merck’s Keytruda (pembrolizumab) met its primary endpoint of progression-free survival at a prespecified interim analysis in first-line PD-L1-negative non-squamous non-small cell lung cancer. This is the first Phase 3 trial of an antibody-drug conjugate combined with an immune checkpoint inhibitor to hit its primary endpoint in first-line NSCLC.

Merck (MRK) closed at $131.07 on July 24. Merck licensed ex-Greater China rights to sac-TMT from Kelun in May 2022, making this readout directly relevant to MRK shareholders even though the trial was conducted exclusively in China. Kelun trades on the Hong Kong exchange as 6990.HK.

What the trial showed

OptiTROP-Lung06 (NCT06711900) was a randomized, open-label, multicenter Phase 3 trial comparing sac-TMT plus pembrolizumab against pembrolizumab plus pemetrexed and platinum chemotherapy, the current first-line standard of care, in patients with PD-L1 tumor proportion score below 1%. At a prespecified interim analysis, the sac-TMT plus Keytruda arm demonstrated a statistically significant and clinically meaningful improvement in PFS as assessed by blinded independent central review. A positive trend in overall survival was also observed. Safety was consistent with established sac-TMT toxicities, with no new signals reported.

Why this matters

This is the first direct proof-of-concept that an ADC can replace platinum-based chemotherapy in a first-line NSCLC standard-of-care regimen. PD-L1-negative patients represent roughly a third of the first-line non-squamous NSCLC population, a group where immunotherapy alone offers limited benefit and chemo remains the backbone. Leerink analysts called it the first direct proof-of-concept for an ADC replacing platinum-based chemo in a 1L NSCLC standard-of-care regimen.

The result also fills a notable gap in Merck’s massive global Phase 3 program for sac-TMT, which previously lacked a registrational study in PD-L1-negative non-squamous NSCLC. Sac-TMT is being evaluated in 10 registrational lung cancer studies, including 5 in China and 5 global multicenter Phase 3 trials. For Merck, sac-TMT is the key pipeline asset intended to extend the company’s oncology dominance beyond Keytruda’s 2028 patent expiry.

How sac-TMT works

Sac-TMT is a TROP2-directed antibody-drug conjugate. The anti-TROP2 monoclonal antibody sacituzumab is linked via a pH-sensitive cleavable linker to a belotecan-derivative topoisomerase I inhibitor payload, with a drug-to-antibody ratio of 7.4. The linker releases the payload inside tumor cells, and the payload also produces a bystander effect against neighboring cancer cells. TROP2 is overexpressed in many solid tumors, making it a popular ADC target alongside the HER2 target used by Enhertu and the TROP2 target used by Datroway, AstraZeneca and Daiichi Sankyo’s competing TROP2 ADC.

The competitive picture

The TROP2 ADC space is crowded. AstraZeneca and Daiichi Sankyo’s Datroway (datopotamab deruxtecan) is the most direct competitor, with the Avanzar trial ongoing in first-line NSCLC. The sac-TMT readout puts competitive pressure on that program. The OptiTROP-Lung05 trial in PD-L1-positive NSCLC was also positive, and together the two trials suggest sac-TMT plus Keytruda may benefit a broad first-line NSCLC population regardless of PD-L1 expression.

What to watch

The key caveat: this is a China-only trial, and Merck has not confirmed it will replicate globally. Full data will be presented at ESMO in October 2026. Jefferies analysts noted the results support sac-TMT plus Keytruda beating standard of care in NSCLC regardless of PD-L1 expression, with the caveat that it is a China-only study. Watch for Merck’s decision on a global registrational trial. For more on the ADC class and its competitive dynamics, see our coverage of the Enhertu CHMP positive opinion and the Trodelvy plus Keytruda CHMP recommendation.

Sources: Kelun-Biotech press release, ClinicalTrials.gov (OptiTROP-Lung06: NCT06711900).