The B7-H3–targeting antibody-drug conjugate tambotatug pelitecan significantly improved overall survival compared with topotecan in patients with small cell lung cancer (SCLC) that had progressed after first-line platinum-based therapy, according to results of the phase III TAISHAN-302 trial reported by Zhao et al in The New England Journal of Medicine.
Study Details
TAISHAN-302 was a multicenter, open-label, randomized superiority trial conducted at 85 sites in China. The study enrolled adults aged 18 to 75 years with SCLC that had progressed or relapsed during or after first-line platinum-based therapy. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0 or 1 and at least one measurable lesion.
Between December 2024 and October 2025, a total of 451 patients were randomly assigned 1:1 to receive tambotatug pelitecan at 2.0 mg/kg on day 1 of each 3-week cycle (n = 225) or topotecan at 1.2 mg/m² on days 1 through 5 of each 3-week cycle (n = 226). The primary endpoint was overall survival.
The median patient age was 62 years, 96.2% of patients had systemic disease, and 34.4% had a history or presence of brain metastases. Previous anti–PD-1 or anti–PD-L1 therapy had been received by 87.1% of patients, and 48.8% had platinum-resistant disease, defined as progression after a chemotherapy-free interval of fewer than 90 days.
Key Results
At the data cutoff of May 20, 2026, median follow-up was 9.2 months (95% confidence interval [CI] = 8.8–10.2 months) with tambotatug pelitecan and 9.5 months (95% CI = 8.9–10.1 months) with topotecan. Median overall survival was 13.3 months (95% CI = 12.1 months to not estimable) with tambotatug pelitecan vs 9.4 months (95% CI = 7.7–10.5 months) with topotecan (hazard ratio [HR] for death = 0.46, 95% CI = 0.35–0.62, P < .001).
Median progression-free survival was 7.4 months (95% CI = 6.1–7.6 months) with tambotatug pelitecan vs 2.8 months (95% CI = 1.8–3.0 months) with topotecan (HR = 0.29, 95% CI = 0.23–0.37, P < .001). Confirmed objective responses occurred in 59.1% and 9.7% of patients, respectively (P < .001). Among patients with intracranial lesions at baseline, intracranial responses were reported in 32% of those receiving tambotatug pelitecan and 3% of those receiving topotecan; median intracranial progression-free survival was 6.1 and 4.2 months, respectively.
Grade 3 or higher adverse events occurred in 124 patients (55.4%) receiving tambotatug pelitecan and 169 (77.9%) receiving topotecan. The most common grade 3 or higher treatment-related events with tambotatug pelitecan included neutropenia (21.0%), leukopenia (19.2%), lymphopenia (13.4%), thrombocytopenia (12.5%), and anemia (10.7%). Interstitial lung disease or pneumonitis occurred in 11 patients (4.9%) in the tambotatug pelitecan group and 3 (1.4%) in the topotecan group. No grade 4 or 5 events were reported.
The investigators concluded: “Among patients with relapsed [SCLC] after platinum-based therapy, treatment with tambotatug pelitecan resulted in longer overall survival, longer progression-free survival, and a higher percentage of patients with an objective response than treatment with topotecan, with a lower incidence of adverse events of grade 3 or higher.”
Li Zhang, MD, of the Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was supported by the Innovative Drug Research and Development National Science and Technology Major Project and by MediLink Therapeutics. For full disclosures of the study authors, visit nejm.org.
