Tambotatug Pelitecan Significantly Improves Overall Survival in Patients With Relapsed Small Cell Lung Cancer

Clinical Summary:

• Design/Population: The multicenter, open-label phase 3 TAISHAN-302 trial compared tambotatug pelitecan, a B7-H3-directed antibody drug conjugate, with topotecan in patients with small cell lung cancer (SCLC) who experienced disease progression after first-line platinum-based therapy.
• Key Outcomes: Tambotatug pelitecan significantly improved overall survival, progression-free survival, and objective response compared with topotecan, reducing the risk of death by 54% and the risk of disease progression or death by 71%. Grade ≥3 adverse events were less frequently reported with tambotatug pelitecan. 
• Clinical Relevance: The findings provide phase 3 evidence supporting tambotatug pelitecan as a potential treatment option for patients with relapsed SCLC following platinum-based therapy. The survival benefit and lower incidence of severe adverse events support further consideration of this B7-H3-targeted approach in the second-line treatment setting. 

Interim results from the phase 3 TAISHAN-302 trial demonstrated that tambotatug pelitecan significantly improved overall survival (OS), progression-free survival (PFS), and objective response compared with topotecan in patients with relapsed small-cell lung cancer (SCLC) following first-line treatment with platinum-based therapy. 

In this multicenter, open-label trial, 451 patients were randomized 1:1 to receive either tambotatug pelitecan (n = 225) or topotecan (n = 226). The primary end point was OS. Key secondary end points included investigator-assessed PFS, confirmed objective response rate (ORR), and safety. 

At analysis, median OS was 13.3 months in the tambotatug pelitecan arm and 9.4 months in the topotecan arm. Tambotatug pelitecan reduced the risk of death by 54% (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.35 to 0.62; P < .001).

Median PFS was 7.4 months and 2.8 months, respectively, corresponding to a 71% reduction in the risk of disease progression or death (HR, 0.29; 95% CI, 0.23 to 0.37; P < .001). The confirmed ORR was 59.1% in the tambotatug pelitecan arm and 9.7% in the topotecan arm (P < .001).

The overall incidence of grade ≥3 adverse events was lower with tambotatug pelitecan than with topotecan, with grade ≥3 events occurring in 55.4% and 77.9% of patients, respectively.

Tambotatug pelitecan is an investigational antibody-drug conjugate designed to target B7-H3, an immune-checkpoint molecule. Earlier clinical studies had demonstrated antitumor activity with the agent in patients with relapsed extensive-stage SCLC, providing the rationale for its evaluation in the phase 3 setting.

The findings from TAISHAN-302 demonstrate that targeting B7-H3 with tambotatug pelitecan can improve survival and tumor response compared with topotecan in patients whose disease has progressed after platinum-based treatment.

Source:

Zhao Y, Liu H, Meng X, et al. Tambotatug pelitecan in small-cell lung cancer after platinum-based therapy. N Engl J Med. Published online: September 12, 2026. doi: 10.1056/nejmoa2610229