The confirmed ORR was 40.0% in cohort 1A and 66.7% in cohort 1B of patients treated with sacituzumab tirumotecan/tagitanlimab for advanced NSCLC.
First-line sacituzumab tirumotecan (sac-TMT) plus tagitanlimab (KL-A167) showed promising efficacy and safety for patients with advanced or metastatic non–small cell lung cancer, according to results from the phase 2 OptiTROP-Lung01 trial (NCT05351788) published in Nature Medicine.
In cohort 1A (n = 40), the median best percentage change in target lesions from baseline was –30.6% (range, –91.8% to 13.0%) and –44.8% (range, –89.6% to 0%) in cohort 1B (n = 63). The confirmed overall response rate (ORR) was 40.0% (95% CI, 24.9%-56.7%) in cohort 1A and 66.7% (95% CI, 53.7%-78.0%) in arm B. The disease control rate (DCR) was 85.0% (95% CI, 70.2%-94.3%) in cohort 1A and 92.1% (95% CI, 82.4%-97.4%) in cohort 1B.
The median progression-free survival (PFS) in cohort 1A was 15.4 months (95% CI, 6.7-17.9). The 6-month PFS rate was 69.2% (95% CI, 51.2%-81.6%), and the 12-month PFS rate was 51.1% (95% CI, 33.5%-66.2%). In cohort 1B, the median PFS was not reached (95% CI, 9.6-not estimable [NE]). The 6-month PFS rate was 84.2% (95% CI, 71.8%-91.4%) and the 12-month PFS rate was 58.4% (95% CI, 44.2%-70.1%).
“In this phase 2 study, the combination of sac-TMT and tagitanlimab exhibited encouraging efficacy and a manageable safety profile in patients with advanced or metastatic NSCLC in the first-line setting,” the authors of the study wrote. “These findings provide a rationale for further investigation of sac-TMT plus immunotherapy in a broad spectrum of patients with NSCLC, as evidenced by the increasing number of phase 3 studies evaluating this combination therapy.”
A total of 103 patients were enrolled. In arms 1A and 1B, the median age was 63 years in both cohorts, most patients were male (85.0% vs 76.2%), and 72.1% vs 60.3% had a smoking history. An ECOG performance status of 1 was noted in 97.5% of patients in cohort 1A and 85.7% in cohort 1B, brain metastases were observed in 12.5% and 3.2%, liver metastases in 10.0% and 14.3%, and squamous cell carcinoma was documented in 55.0% and 46.0%.
The coprimary end points of the trial included safety and ORR. Secondary end points included PFS, duration of response, and DCR according to RECIST v1.1 criteria.
In cohort 1A, sac-TMT was given at 5 mg/kg every 3 weeks plus tagitanlimab at 1200 mg every 3 weeks in each 3-week cycle. In cohort 1B, patients were given sac-TMT at 5 mg/kg every 2 weeks plus tagitanlimab at 900 mg every 2 weeks in each 4-week cycle.
Treatment-related adverse effects (TRAEs) in cohort 1A were observed in 95.0% of patients and in 96.8% in cohort 1B. Grade 3 or higher TRAEs were noted in 42.5% of patients in cohort 1A and 58.7% in cohort 1B.
Dose reductions of sac-TMT due to TRAEs were observed in 17.5% of patients in cohort 1A and 42.9% in cohort 1B. Treatment discontinuations due to any drug were observed in 2.5% and 6.3%, and discontinuation of sac-TMT was noted in 2 patients in cohort 1B, while tagitanlimab discontinuation occurred in 2.5% in cohort 1A and 3.2% in cohort 1B.
Treatment-related serious AEs occurred in 10.0% of patients in cohort 1A and 20.6% in cohort 1B.
The most common TRAEs of grade 3 or higher in cohort 1A and 1B, respectively were decreased neutrophil count (30.0% and 34.9%), decreased white blood cell count (5.0% and 19.0%), anemia (5.0% and 19.0%), rash (5.0% and 7.9%), stomatitis (0% and 9.5%), and drug eruption (7.5% and 0%).
Immune-related AEs (irAEs) occurred in 25.0% of patients in cohort 1A and 39.7% in cohort 1B. Grade 3 or higher irAEs were noted in 7.5% of patients in cohort 1A and 12.7% in cohort 1B, with the most common between cohorts being rash (12.5% and 14.3%), increased alanine aminotransferase (ALT) (0% and 11.1%), hypothyroidism (2.5% and 7.9%), increased aspartate aminotransferase (AST) (0% and 6.3%) and hyperthyroidism (0% and 6.3%).
Reference
Hong S, Wang Q, Cheng Y, et al. First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial. Nat Med. Published online August 19, 2025. doi:10.1038/s41591-025-03883-5