Kelun-Biotech’s Phase III OptiTROP-Lung06 trial met its primary endpoint, showing sacituzumab tirumotecan plus pembrolizumab significantly improved progression-free survival over standard first-line chemoimmunotherapy in PD-L1-negative non-squamous NSCLC.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Kelun-Biotech reported positive Phase III results from the OptiTROP-Lung06 study, showing that its TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870) combined with Keytruda (pembrolizumab) significantly improved progression-free survival (PFS) compared with the current first-line standard of care in patients with PD-L1-negative, driver gene-negative, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).
The findings position the ADC-immunotherapy combination as a potential new frontline treatment option for a patient population that has historically derived limited benefit from immunotherapy alone.
ADC-Immunotherapy Strategy Expands Frontline Treatment Options
Sacituzumab tirumotecan is a TROP2-targeted antibody-drug conjugate that delivers a topoisomerase I inhibitor directly to tumor cells while also producing a bystander effect against neighboring cancer cells. Combining the ADC with pembrolizumab aims to enhance both direct tumor cell killing and anti-tumor immune responses.
Patients with PD-L1 tumor proportion score (TPS) below 1% typically receive pembrolizumab with platinum-based chemotherapy as first-line treatment. Despite improvements in survival, outcomes remain suboptimal, creating a need for more effective chemotherapy-sparing approaches.
Phase III OptiTROP-Lung06 Met Its Primary Endpoint
OptiTROP-Lung06 (NCT06711900) is a randomized, open-label, multicenter Phase III study comparing sacituzumab tirumotecan plus pembrolizumab with pembrolizumab plus pemetrexed and platinum chemotherapy in previously untreated patients with PD-L1-negative locally advanced or metastatic non-squamous NSCLC.
At a prespecified interim analysis, an Independent Data Monitoring Committee determined that the study met its primary endpoint. The investigational combination demonstrated a statistically significant and clinically meaningful improvement in progression-free survival based on blinded independent central review. Investigators also observed a positive trend in overall survival, although final overall survival data remain immature.
The safety profile was consistent with previous studies of sacituzumab tirumotecan, and investigators reported no new safety signals. Based on these findings, Kelun-Biotech plans to engage China’s Center for Drug Evaluation (CDE) regarding a potential regulatory submission.
Builds on Earlier Phase III Success
The positive OptiTROP-Lung06 results follow the earlier success of the OptiTROP-Lung05 Phase III trial (NCT06448312), which evaluated the same combination in PD-L1-positive first-line NSCLC. That study also met its primary endpoint, supporting a regulatory application in China.
Together, the two Phase III studies suggest that sacituzumab tirumotecan plus pembrolizumab could benefit a broad spectrum of patients with first-line non-squamous NSCLC regardless of PD-L1 expression, potentially reducing reliance on conventional platinum-based chemotherapy.
Investigators Highlight Clinical Significance
Lead investigator Professor Caicun Zhou said the study represents an important advance for patients with PD-L1-negative NSCLC, where durable survival improvements remain limited despite current immunotherapy-based regimens. He noted that the results provide strong clinical evidence supporting the combination of a TROP2-directed ADC with immune checkpoint inhibition as a new frontline treatment strategy.
Kelun-Biotech CEO Dr. Michael GE said the consistent Phase III results across both PD-L1-positive and PD-L1-negative populations reinforce the complementary activity of sacituzumab tirumotecan and pembrolizumab and support broader clinical use across first-line NSCLC.
Regulatory Path Forward
Sacituzumab tirumotecan is already approved in China for four indications, including advanced breast cancer and EGFR-mutated NSCLC, and is the first TROP2 ADC approved for lung cancer. Kelun-Biotech has licensed global development and commercialization rights outside Greater China to Merck & Co., Inc. (MSD).
The company is evaluating the ADC in 10 registrational lung cancer studies, while MSD is conducting 17 global Phase III trials across multiple tumor types. The latest Phase III success strengthens the case for expanding ADC-immunotherapy combinations into earlier lines of treatment for NSCLC and could influence future first-line treatment standards if regulatory reviews confirm the clinical benefit.
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About the Writer
Shaik Yasmeen (LinkedIn) is a PharmD graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.