Sac-TMT Combo Shows Benefit in Advanced Lung Cancer Treatment

Sacituzumab tirumotecan (sac-TMT), in combination with Keytruda (pembrolizumab), as a first-line treatment for PD-L1-positive advanced non-small cell lung cancer, has demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, the study's primary endpoint, according to a news release from Kelen-Biotech Biopharmaceutical.

Results come from the phase 3 OptiTROP-Lung05 study in which a positive trend in overall survival was also observed.

This marks the first phase 3 clinical trial of antibody-drug conjugate combined with immune checkpoint inhibitor to reach its primary endpoint in the first-line treatment of non-small cell lung cancer.

What is the phase 3 OptiTROP-Lung05 study design?

The OptiTROP-Lung05 study is a randomized, open-label phase 3 trial taking place at multiple centers to understand whether combining sac-TMT with Keytruda can help people with locally advanced or metastatic non-small cell lung cancer whose tumors have PD-L1 levels of 1% or higher. Researchers are comparing this combination with Keytruda alone to see which option works better and stays safe for patients.

During a planned early look at the results, the combination of sac-TMT and Keytruda showed a meaningful improvement in the time patients lived without their cancer growing. Because of these findings, the company developing sac-TMT plans to speak with China’s Center for Drug Evaluation about submitting a supplemental new drug application so the treatment can be reviewed for potential approval.

A supplemental new drug application, or sNDA, is a request asking a drug agency to approve a new use or update for a medicine that is already on the market.

What is sac-TMT and its previous indications?

Sac-TMT is an antibody-drug conjugate designed to target TROP2, a protein found on many solid tumors including lung, breast, gastric and gynecologic cancers. Once sac-TMT binds to TROP2 on tumor cells, it is taken inside the cell and releases its chemotherapy payload, KL610023. This drug causes DNA damage that leads to cell-cycle arrest and apoptosis, and some of the drug also enters the tumor’s surrounding space. Because KL610023 can pass through cell membranes, it may also kill nearby cancer cells, known as a bystander effect.

In 2022, the company developing sac-TMT granted Merck the exclusive rights to develop and commercialize the treatment outside Greater China.

In China, sac-TMT is already approved for three uses in adult patients: unresectable locally advanced or metastatic triple negative breast cancer after at least two prior systemic therapies, EGFR mutation-positive locally advanced or metastatic non-squamous non-small cell lung cancer after EGFR-targeted therapy and platinum chemotherapy, and EGFR mutation-positive locally advanced or metastatic non-squamous lung cancer after EGFR-targeted therapy. It is the first TROP2 antibody-drug conjugate approved for lung cancer anywhere in the world.

A supplemental new drug application for unresectable locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer after prior endocrine and other systemic therapies has been accepted by China’s drug regulator and granted priority review.

So far, the company has launched nine registrational studies in China. Merck has 15 ongoing phase 3 global trials studying sac-TMT alone or in combination with Keytruda or other cancer therapies in several tumor types.

What is PD-L1 advanced non-small cell lung cancer?

According to the National Cancer Institute’s website, PD-L1–positive advanced non-small cell lung cancer refers to disease in which tumors show higher-than-normal levels of PD-L1, a protein that can suppress the immune system when it binds to PD-1 on T cells. Immune checkpoint inhibitors block this interaction, helping T cells attack cancer cells.

“Advanced” means the cancer has spread or is unlikely to be cured, though treatment can often control it for years and ease symptoms. Non-small cell lung cancer, the most common type of lung cancer, includes adenocarcinoma, squamous cell carcinoma and large cell carcinoma.

Reference

1. “Kelun-Biotech Announces Phase III Trial of Sac-TMT in Combination with KEYTRUDA® (pembrolizumab) as First-Line Treatment for PD-L1-Positive NSCLC Met Primary Endpoint.” Kelun-Biotech. News Release. Nov. 24, 2025

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