Sac-TMT Combo Meets PFS End Point in PD-L1–Negative NSCLC Trial

Sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870) plus pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) compared with chemotherapy plus pembrolizumab as first-line treatment for patients with PD-L1–negative locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 OptiTROP-Lung06 trial at a prespecified interim analysis, according to a news release from Kelun-Biotech.¹

What did OptiTROP-Lung06 show?

At a prespecified interim analysis, sac-TMT plus pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in PFS as assessed by blinded independent central review (BICR) compared with pembrolizumab plus pemetrexed and platinum-based chemotherapy. A positive trend in overall survival (OS) was also observed with the sac-TMT combo.

The safety profile of the combination appeared consistent with previously reported studies, with no new safety signals identified. According to the developers, this is the first phase 3 study of an antibody-drug conjugate (ADC) combined with an immune checkpoint inhibitor to meet its primary end point in the first-line treatment of driver gene–negative and PD-L1–negative nonsquamous NSCLC.

“For patients with driver gene‑negative and PD‑L1‑negative NSCLC, immunotherapy combined with chemotherapy remains the current standard first-line treatment and has improved patient outcomes to some extent. However, long-term survival benefit remains limited. The achievement of positive results in the phase 3 OptiTROP-Lung06 study represents an important breakthrough in the first-line treatment of PD-L1–negative NSCLC,” said national lead principal investigator Caicun Zhou, MD, PhD, professor at Shanghai East Hospital, Tongji University, in the press release.¹ “These results not only provide robust clinical evidence supporting the ‘ADC plus immunotherapy’ strategy of sac-TMT in combination with pembrolizumab, but also have the potential to offer these patients a new first-line treatment option beyond the current standard of care, with the promise of improved survival outcomes.”

What is the OptiTROP-Lung06 trial design?

OptiTROP-Lung06 is a randomized, open-label, multicenter phase 3 study evaluating sac-TMT plus pembrolizumab vs chemotherapy plus pembrolizumab as first-line treatment for patients with locally advanced or metastatic non–squamous NSCLC who have a PD-L1 tumor proportion score of less than 1%. The primary end point is PFS by BICR assessment; secondary end points include OS and safety. The comparator arm consisted of pembrolizumab plus pemetrexed and platinum-based chemotherapy, the current first-line standard of care in this setting.

The company plans to communicate these results with the Center for Drug Evaluation of China’s National Medical Products Administration.

What is sac-TMT, and how is it being developed?

Sac-TMT is a TROP2-directed ADC composed of a humanized anti-TROP2 monoclonal antibody that harnesses a bifunctional linker to a belotecan-derivative topoisomerase I inhibitor payload, with a drug-to-antibody ratio of 7.4. With its KL610023 payload, the drug can create a bystander effect on adjacent tumor cells.

Sac-TMT plus pembrolizumab previously met the primary end point of the phase 3 OptiTROP-Lung05 study (NCT06448312) in first-line PD-L1–positive NSCLC, with results presented at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO) and published in The Lancet.^2,3 Sac-TMT is approved for several indications in China, including triple-negative breast cancer and EGFR-mutant nonsquamous NSCLC. It is the first TROP2 ADC approved for lung cancer.

“The positive results of both the OptiTROP-Lung05 and OptiTROP-Lung06 studies confirm the strong synergetic effect of sac-TMT combined with pembrolizumab, supporting the potential of this combination regimen to benefit the broad first-line NSCLC population and bringing new treatment opportunities to patients with different PD-L1 expression levels,” Michael Ge, chief executive officer at Kelun-Biotech, concluded.¹

References

1. Kelun-Biotech announces phase III study of sacituzumab tirumotecan (sac-TMT) in combination with pembrolizumab as first-line treatment for PD-L1-negative non-squamous NSCLC met primary endpoint. News release. Sichuan Kelun-Biotech Biopharmaceutical Co, Ltd. July 14, 2026. Accessed July 15, 2026. https://tinyurl.com/4hrwvafs
2. Zhou C, Xiong A, Yao W, et al. Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab versus pembrolizumab as first-line treatment for PD-L1–positive advanced non-small cell lung cancer (NSCLC): results from the randomized phase 3 OptiTROP-Lung05 study. J Clin Oncol. 2026;44(suppl 16):8506. doi:10.1200/JCO.2026.44.16_suppl.8506
3. Xiong A, Yao W, Zheng W, et al. Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial. Lancet. May 29, 2026. doi:10.1016/S0140-6736(26)00968-2