Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus chemotherapy (chemo) plus pembrolizumab (P) as first-line (1L) treatment for PD-L1-negative advanced non-squamous (nsq) NSCLC: Randomized phase 3 OptiTROP-Lung06 study

doi:10.1056/nejmoa2611280

OptiTROP-Lung06

Patient / Population Intervention / Exposure Comparison Outcome

In patients with previously untreated PD-L1-negative advanced non-squamous NSCLC, sacituzumab tirumotecan plus pembrolizumab improved progression-free survival compared with chemotherapy plus pembrolizumab.

N

455patients

Design

Randomised 1:1 phase 3 trial in treatment-naïve locally advanced or metastatic non-squamous NSCLC without EGFR/ALK alterations and PD-L1 TPS <1% (22C3 assay), comparing sacituzumab tirumotecan plus pembrolizumab with chemotherapy plus pembrolizumab (NCT06711900).

Endpoint

Progression-free survival per RECIST 1.1 assessed by blinded independent central review.

ResultMedian PFS by BICR 15.0 vs 5.7 mo with sacituzumab tirumotecan plus pembrolizumab vs chemotherapy plus pembrolizumab (HR 0.49; 95% CI 0.36-0.65; P<0.0001) at a median follow-up of 9.7 mo. OS was immature (HR 0.58; 95% CI 0.38-0.88). ORR by BICR 50.2% vs 47.3%. Median DoR 13.6 vs 6.8 mo (HR 0.47; 95% CI 0.29-0.77). Grade ≥3 TEAEs 47.6% vs 60.6%, including neutrophil count decreased 19.7% vs 28.8%, white blood cell count decreased 9.6% vs 16.4%, anaemia 6.1% vs 20.4% and platelet count decreased 3.9% vs 14.6%. Grade ≥3 stomatitis occurred in 2.2%.

Zhou F, Meng X, Ding Q, et al. N Engl J Med. 2026; published online 25 October. 10.1056/nejmoa2611280

Discussion & critique

This preplanned interim analysis shows a large progression-free survival benefit by blinded central review, together with fewer grade 3 or higher haematological adverse events than chemotherapy plus pembrolizumab. With a median follow-up of 9.7 months the overall survival data are immature and no P value is given for them, so the benefit rests on a surrogate endpoint for now. Response rates were similar between the arms, which suggests the PFS gain comes mainly from more durable responses. The abstract does not say whether treatment was open label, does not name the chemotherapy regimen, and gives no subgroup, quality-of-life or discontinuation data; the trial was funded by Sichuan Kelun-Biotech.