Sacituzumab Tirumotecan Plus Pembrolizumab Meets Phase III Endpoint in First-Line PD-L1-Negative Non-Squamous NSCLC
Kelun-Biotech has announced positive phase III results for sacituzumab tirumotecan, also known as sac-TMT or SKB264/MK-2870, in combination with pembrolizumab as first-line treatment for patients with PD-L1-negative locally advanced or metastatic non-squamous non-small cell lung cancer.
The phase III OptiTROP-Lung06 trial met its primary endpoint of progression-free survival at a prespecified interim analysis, according to the company. Sac-TMT plus pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in PFS compared with pembrolizumab plus pemetrexed and platinum-based chemotherapy. A positive trend in overall survival was also observed, although detailed survival data were not included in the announcement.
The company stated that no new safety signals were identified and that the safety profile of sac-TMT plus pembrolizumab was consistent with previously reported studies.
A Head-to-Head Test Against Standard First-Line Therapy
OptiTROP-Lung06 is a randomized, open-label, multicenter phase III trial evaluating whether replacing conventional pemetrexed/platinum chemotherapy with a TROP2-directed antibody-drug conjugate could improve outcomes when combined with pembrolizumab.
The trial enrolled patients with locally advanced or metastatic non-squamous NSCLC with PD-L1 tumor proportion score below 1%. The control arm received pembrolizumab with pemetrexed and platinum-based chemotherapy, a commonly used first-line approach for patients without actionable driver alterations.
The primary endpoint was PFS assessed by blinded independent central review. Secondary endpoints included overall survival, safety, and other measures.
Kelun-Biotech described OptiTROP-Lung06 as the first phase III clinical study of an ADC combined with an immune checkpoint inhibitor to meet its primary endpoint in the first-line treatment of driver gene-negative and PD-L1-negative non-squamous NSCLC.
Why the PD-L1-Negative Population Matters
PD-L1-negative non-squamous NSCLC remains a difficult first-line treatment setting.
Patients with PD-L1 TPS below 1% are generally less likely to benefit from immune checkpoint inhibitor monotherapy. For many of these patients, immunotherapy is used together with chemotherapy to increase the chance of disease control.
The OptiTROP-Lung06 strategy is different. Instead of pairing pembrolizumab with conventional chemotherapy, the investigational arm pairs pembrolizumab with sac-TMT, a TROP2-directed ADC designed to deliver a cytotoxic payload more selectively to tumor cells.
According to Kelun-Biotech, this approach may combine the targeted tumor-cell killing of an ADC with immune activation through pembrolizumab. The company suggested that this could help unlock immunotherapy benefit in patients with PD-L1-negative or limited immune responses.
What Is Sacituzumab Tirumotecan?
Sac-TMT is a human TROP2-directed antibody-drug conjugate developed by Kelun-Biotech. It is also known globally as MK-2870 through Merck’s development program outside Greater China.
The ADC uses a humanized anti-TROP2 monoclonal antibody linked to a belotecan-derivative topoisomerase I inhibitor payload. The company describes the linker as bifunctional, designed to maximize payload delivery through stable antibody connection and pH-sensitive cleavage in the lysosome.
Sac-TMT has a reported drug-to-antibody ratio of 7.4. After binding TROP2 on tumor cells, the ADC is internalized and releases its payload intracellularly. The payload induces DNA damage, leading to cell-cycle arrest and apoptosis. Because the payload is membrane permeable, sac-TMT may also produce a bystander effect in the tumor microenvironment.
Building on OptiTROP-Lung05
The positive OptiTROP-Lung06 announcement follows another phase III success for the same combination strategy.
Kelun-Biotech previously reported that OptiTROP-Lung05, a registrational phase III study of sac-TMT plus pembrolizumab as first-line treatment for PD-L1-positive NSCLC, met its primary endpoint. Those findings supported a new indication application to China’s Center for Drug Evaluation and were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in The Lancet, according to the company.
Together, OptiTROP-Lung05 and OptiTROP-Lung06 suggest that sac-TMT plus pembrolizumab is being developed across a broader first-line NSCLC population, including both PD-L1-positive and PD-L1-negative disease.
Regulatory and Development Context
Kelun-Biotech plans to communicate with China’s Center for Drug Evaluation of the National Medical Products Administration based on the OptiTROP-Lung06 results.
Sac-TMT is already approved and marketed in China for four indications, including triple-negative breast cancer, EGFR-mutant non-squamous NSCLC after prior therapies, and HR-positive/HER2-negative breast cancer after prior endocrine therapy and chemotherapy. The company also stated that sac-TMT is the world’s first TROP2 ADC approved for marketing in lung cancer.
In May 2022, Kelun-Biotech licensed exclusive rights to Merck & Co. to develop, manufacture, and commercialize sac-TMT outside Greater China. The drug is now being evaluated in multiple registrational studies in lung cancer, including trials led by Kelun-Biotech in China and global phase III studies led by Merck.
What Still Needs to Be Seen
The announcement is important, but full clinical interpretation will require detailed data.
The company did not report median PFS, hazard ratios, response rates, duration of response, overall survival maturity, subgroup outcomes, treatment exposure, or detailed adverse-event rates in the press release. These data will be needed to understand the magnitude of benefit and how the regimen compares with existing first-line standards.
Safety will also be important, especially because ADCs can carry risks related to cytopenias, gastrointestinal toxicity, stomatitis, fatigue, neuropathy, and interstitial lung disease depending on platform and payload. The company reported no new safety signals, but complete safety tables will be needed.
The Bottom Line
The phase III OptiTROP-Lung06 trial met its primary endpoint in first-line PD-L1-negative locally advanced or metastatic non-squamous NSCLC.
Sacituzumab tirumotecan plus pembrolizumab significantly improved PFS compared with pembrolizumab plus pemetrexed and platinum chemotherapy, with a positive overall survival trend reported by Kelun-Biotech.
The result supports continued development of TROP2 ADC plus immunotherapy strategies in first-line NSCLC, including populations historically less responsive to immunotherapy alone.
Full data presentation or publication will be essential to define the clinical magnitude, safety profile, and potential role of sac-TMT plus pembrolizumab in the first-line NSCLC treatment landscape.
References
- Kelun-Biotech. Kelun-Biotech announces phase III study of sacituzumab tirumotecan in combination with pembrolizumab as first-line treatment for PD-L1-negative non-squamous NSCLC met primary endpoint. Published July 14, 2026.