Sac-TMT Plus Keytruda Extends Progression-Free Survival in PD-L1+ NSCLC

Treatment with sac-TMT (sacituzumab tirumotecan) plus Keytruda (pembrolizumab) significantly improved progression-free survival compared with Keytruda alone when used as a first-line treatment for patients with PD-L1–positive advanced non-small cell lung cancer (NSCLC), according to findings from the phase 3 OptiTROP-Lung05 trial presented at the 2026 ASCO Annual Meeting.

Findings were presented by Dr. Caicun Zhou, of Shanghai East Hospital and Tongji University School of Medicine in Shanghai, China.

Key Efficacy and Survival Outcomes

At a median follow-up of 10.5 months, patients who received Keytruda alone experienced a median progression-free survival of 5.7 months. In the sac-TMT plus Keytruda group, median progression-free survival had not yet been reached at the time of the analysis, indicating many patients were still benefiting from treatment without disease progression.

Researchers reported that the combination reduced the risk of disease progression or death by 65% compared with Keytruda alone.

The benefit was seen across multiple patient groups, including those with different levels of PD-L1 expression and different tumor types.

The objective response rate, which measures how many patients experienced tumor shrinkage, was 70.2% with sac-TMT plus Keytruda compared with 42.0% with Keytruda alone.

Additionally, nearly half of patients receiving the combination treatment experienced deep responses, defined as at least a 50% reduction in tumor size. Deep responses occurred in 49.0% of patients treated with sac-TMT plus Keytruda compared with 25.9% of patients who received Keytruda alone.

Although overall survival data are still early, researchers observed a trend favoring the combination. At 12 months, 80.4% of patients who received sac-TMT plus Keytruda were alive compared with 68.9% of those treated with Keytruda alone.

Trial Design and Patient Population

OptiTROP-Lung05 was a phase 3 clinical trial that evaluated sac-TMT, a TROP2-directed antibody-drug conjugate, in combination with Keytruda.

The study enrolled 413 patients with locally advanced or metastatic NSCLC who had not received prior systemic treatment for their disease. Patients were required to have PD-L1 expression of at least 1%, an ECOG performance status of 0 or 1, and no EGFR or ALK alterations.

Participants were randomly assigned to receive either sac-TMT plus Keytruda (208 patients) or Keytruda alone (205 patients).

The primary goal of the study was to compare progression-free survival, which is the length of time patients live without their cancer growing or spreading.

Safety

Researchers reported that the safety profile of sac-TMT plus Keytruda was manageable and consistent with what has previously been seen with each treatment individually. No new safety concerns were identified.

Serious treatment-related side effects occurred more frequently with the combination than with Keytruda alone.

The most common side effects seen with sac-TMT plus Keytruda included:

• Anemia
• Low neutrophil counts
• Low white blood cell counts
• Hair loss
• Mouth sores

Researchers also reported eye-related side effects in some patients receiving sac-TMT as well as infusion-related reactions.

Among immune-related side effects commonly associated with Keytruda, hypothyroidism and pneumonitis occurred slightly more often in patients who received the combination.

Clinical Implications and Next Steps

For many patients with PD-L1–positive advanced NSCLC, first-line treatment with immunotherapy alone can result in progression-free survival of approximately 5 to 8 months.

The findings from OptiTROP-Lung05 suggest that adding sac-TMT to Keytruda may offer a more effective first-line treatment option by helping patients live longer without disease progression while also increasing the likelihood of tumor shrinkage.

"The safety profile was manageable and consistent with the known profiles of the individual agents, with no new safety signals observed. The results of the OptiTROP-Lung05 study support sac-TMT plus Keytruda as a potential new first-line treatment option for patients with PD-L1–positive advanced non-small cell lung cancer," said Zhou, during the presentation.

However, researchers noted that overall survival data remain immature, meaning additional follow-up will be needed to determine whether the progression-free survival benefit ultimately translates into a longer life expectancy for patients receiving the combination.

References

1. “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” by Dr. Caicun Zhou, et al., presented at the 2026 ASCO Annual Meeting.
2. “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” by Dr. Aizhong Xiong, et al., The Lancet.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.