Kelun's Sac-TMT Plus Keytruda Cuts Progression Risk 51% in PD-L1-Negative First-Line Lung Cancer

Sichuan Kelun-Biotech Biopharmaceutical said on Oct. 25 that its TROP2-directed antibody-drug conjugate sacituzumab tirumotecan, given with Merck's Keytruda, cut the risk of disease progression or death by 51% compared with Keytruda plus platinum chemotherapy in patients with untreated, PD-L1-negative advanced non-squamous non-small cell lung cancer. The Chengdu-based company reported the Phase III OptiTROP-Lung06 results in an oral presentation at the European Society for Medical Oncology Congress in Madrid, with simultaneous publication in The New England Journal of Medicine.

Disease and treatment background

Non-squamous NSCLC without a targetable driver mutation is usually treated in the first line with a PD-1 inhibitor such as pembrolizumab, either alone or with platinum-based chemotherapy, depending on PD-L1 expression. Patients whose tumors express little or no PD-L1 tend to benefit less from immunotherapy alone, so the chemotherapy-immunotherapy combination used as the comparator in OptiTROP-Lung06 has been the standard regimen for this group.

Sac-TMT is an antibody-drug conjugate that targets TROP2, a protein found on the surface of many epithelial cancers, and delivers a cytotoxic payload into tumor cells. The trial tested whether replacing platinum doublet chemotherapy with the ADC, while keeping pembrolizumab, would improve outcomes in the PD-L1-negative population. Kelun first disclosed in mid-July that the study had met its primary endpoint; the Madrid presentation is the first full public readout of the data.

The drug is already approved in China for four indications, including two lung cancer settings in EGFR-mutant non-squamous NSCLC after progression on EGFR tyrosine kinase inhibitors, as well as triple-negative and HR-positive, HER2-negative breast cancer. Two of those indications are on China's National Reimbursement Drug List.

Industry implications

The result extends a pattern of TROP2 ADCs moving from late-line monotherapy into first-line combinations with checkpoint inhibitors. Kelun had already reported an earlier first-line win in PD-L1-positive disease in its OptiTROP-Lung05 study, and China's National Medical Products Administration has granted priority review to a filing for sac-TMT plus pembrolizumab in first-line NSCLC with PD-L1 expression of 1% or higher. OptiTROP-Lung06 now covers the PD-L1-negative segment, which would give the regimen data across the PD-L1 spectrum in China.

For drug developers, the trial is notable because the ADC replaced chemotherapy rather than being added to it. If confirmed in global studies, a chemotherapy-free first-line approach in PD-L1-negative disease would change how oncologists sequence platinum doublets and could shift chemotherapy use into later lines.

The data come with limits. OptiTROP-Lung06 was conducted only in China, the analysis is an interim one, overall survival is not mature and the safety comparison has so far been described only qualitatively. Regulators outside China will look for confirmation from multiregional trials.

Competitive and supply chain implications

Kelun granted Merck, known as MSD outside the U.S. and Canada, exclusive rights in May 2022 to develop, manufacture and commercialize sac-TMT outside Greater China. Kelun says Merck is running 18 global Phase III studies of the drug, alone or with pembrolizumab and other agents. Merck has already reported a positive Phase III result for sac-TMT in previously treated endometrial cancer in its TroFuse-005 trial, and its lung program includes studies in EGFR-mutant disease, PD-L1-high first-line disease and the adjuvant setting.

The TROP2 class is crowded. Gilead Sciences markets sacituzumab govitecan as Trodelvy, and AstraZeneca and Daiichi Sankyo market datopotamab deruxtecan as Datroway, with both companies running lung cancer programs. Bispecific antibodies that combine PD-1 and VEGF blockade are also competing for first-line NSCLC. Pairing sac-TMT with Keytruda, the most widely used checkpoint inhibitor in lung cancer, gives Merck a combination it controls end to end outside China, which could matter as Keytruda's main patents approach expiry later this decade.

On the manufacturing side, ADCs require antibody production, linker-payload chemistry and conjugation capacity, typically split across specialized facilities and contract manufacturers. Broader first-line use would raise demand for highly potent payload handling and conjugation capacity in both Chinese and Western supply networks.

Regional implications

In China, the readout strengthens Kelun's domestic position. The company reports six Breakthrough Therapy Designations from the NMPA for sac-TMT and nine registrational studies in the country, and it previously said it would share the OptiTROP-Lung06 data with the regulator. A first-line PD-L1-negative label would add to the NSCLC indications already under review.

For the U.S., Europe and Japan, the result is supportive evidence rather than a filing basis on its own. Approvals in those regions will likely depend on Merck's global trials, which enroll more diverse populations and use standards of care common in Western practice. The OptiTROP-Lung06 data also add to the growing number of oncology assets licensed out of China whose first pivotal evidence comes from Chinese trials.

What comes next

• Publication details in The New England Journal of Medicine, including per-arm safety data, will be scrutinized by clinicians and regulators.
• Kelun is expected to pursue a Chinese regulatory filing for the PD-L1-negative first-line indication after sharing the data with the NMPA.
• NMPA decisions on the priority-review filings for PD-L1-positive first-line NSCLC and first-line triple-negative breast cancer are pending.
• Further overall survival analyses from OptiTROP-Lung06 will determine whether the early survival trend holds.
• Readouts from Merck's global TroFuse program, including lung cancer studies, will decide the path to approvals outside China.

Sources

• Kelun-Biotech: Results of Phase III OptiTROP-Lung06 study presented at ESMO and published in NEJM (Oct. 25, 2026)
• ClinicalTrials.gov: OptiTROP-Lung06 (NCT06711900)

Image: Histopathology of poorly differentiated lung adenocarcinoma, by Mikael Häggström, M.D., via Wikimedia Commons, CC0. Cropped and edited by Credence Research.