Sacituzumab Tirumotecan Plus Pembrolizumab Improves PFS in NSCLC

The phase 3 OptiTROP-Lung05 trial (NCT06448312) evaluating the efficacy and safety profile of sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870) in combination with pembrolizumab (Keytruda) vs pembrolizumab monotherapy as first-line treatment of patients with PD-L1–positive, locally advanced or metastatic non–small cell lung cancer (NSCLC) has demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), meeting its primary end point.^1,2

This is the first phase 3 clinical trial of an antibody-drug conjugate (ADC) combined with an immune checkpoint inhibitor to achieve its primary end point in the first-line treatment of NSCLC.

The OptiTROP-Lung05 study is a randomized, open-label, multicenter trial. At a prespecified interim analysis, the sac-TMT combination therapy demonstrated a statistically significant and clinically meaningful improvement in PFS. Based on the results from the interim analysis, Sichuan Kelun-Biotech Biopharmaceutical Co plans to pursue a supplemental new drug application with the Center for Drug Evaluation of the National Medical Products Administration of China.

OptiTROP-Lung05 Trial

The OptiTROP-Lung05 trial has an estimated total enrollment of 406 patients and an estimated completion date of November 2026.

Patient inclusion criteria include but are not limited to having locally advanced stage 3b/3c NSCLC, or metastatic stage 4 NSCLC that is not amenable to radical surgery, and/or radical radiotherapy regardless of concurrent chemotherapy, no prior systemic anticancer therapy for locally advanced or metastatic disease, participants whose tumors are PD-L1 tumor proportion score of at least 1%, and being aged 18 to 75 years.

Patient exclusion criteria include, but are not limited to, having an active second malignancy, uncontrolled or clinically significant cardiovascular disease, a history of noninfectious pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD, and active infection requiring systemic therapy within 2 weeks of randomization.

Sac-TMT is already approved in China for the treatment of patients with EGFR-mutant NSCLC in the second-line and later settings and has achieved dual benefits in PFS and overall survival (OS) in the EGFR–tyrosine kinase inhibitor (TKI)-resistant lung cancer population. Sac-TMT is the first ADC to show clinically meaningful benefits in both PFS and OS compared with platinum doublet chemotherapy, according to results published in The New England Journal of Medicine and BMJ from the OptiTROP-Lung04 and OptiTROP-Lung03 trials, respectively.

OptiTROP-Lung04 Trial

In the phase 3 OptiTROP-Lung04 trial (NCT05870319),³ patients were randomly assigned 1:1 to receive sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. A total of 376 patients were enrolled, with 188 patients in each arm. After a median follow-up of 18.9 months, the median PFS was 8.3 months in the sac-TMT arm vs 4.3 months in the chemotherapy arm (HR, 0.49; 95% CI, 0.39-0.62). OS was longer in the sac-TMT arm vs the chemotherapy arm (HR, 0.60; 95% CI, 0.44-0.82; P =.001). Treatment-related adverse events of grade 3 or less occurred in 58% of patients in the sac-TMT arm vs 53.8% of patients in the chemotherapy arm.

OptiTROP-Lung03 Trial

The objective of the OptiTROP-Lung03 trial (NCT05631262)⁴ was to compare the efficacy and safety of sac-TMT with docetaxel in patients with locally advanced or metastatic EGFR-mutated NSCLC after previous treatment failure with EGFR-TKI and platinum-based chemotherapy. The median follow-up was 12.2 months. The objective response rate was significantly higher in the sac-TMT arm vs the docetaxel arm (45% vs 16%). The median PFS was 6.9 months in the sac-TMT arm vs 2.8 months in the docetaxel arm.

Sac-TMT is currently being evaluated in 10 registrational studies for lung cancer, including 5 studies in China and 5 global, multicenter, phase 3 studies.¹

REFERENCES

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. News release. Kelun Biotech. November 24, 2025. Accessed November 25, 2025. https://tinyurl.com/nhc2c6kt

2.A study of SKB264 in combination with pembrolizumab versus pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated May 30, 2025. Accessed November 25, 2025. https://clinicaltrials.gov/study/NCT06448312

3.Fang W, Wu L, Meng X et al. Sacituzumab tirumotecan in EGFR-TKI-resistant, EGFR-mutated advanced NSCLC. N Engl J Med. Published online October 19, 2025. doi:10.1056/NEJMoa2512071.

4.Fang W, Li X, Wang Q et al. Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial. BMJ. 2025;389:e085680. doi:10.1136/bmj-2025-085680