TAISHAN-302: B7-H3 ADC Tambotatug Pelitecan Cuts Death Risk 54% in Relapsed SCLC

The phase III TAISHAN-302 trial has established B7-H3 (搜索)搜索该靶点 as a therapeutic target in small-cell lung cancer (搜索)搜索该疾病, showing that the antibody-drug conjugate tambotatug pelitecan (搜索)搜索该药品 (Tam-Peli) significantly improved overall survival, progression-free survival and objective response compared with topotecan查看药品详情 in patients whose disease progressed after first-line platinum-based therapy. Results were published in The New England Journal of Medicine on September 12, 2026.

Median overall survival reached 13.3 months with Tam-Peli versus 9.4 months with topotecan查看药品详情, a hazard ratio for death of 0.46 (95% CI, 0.35-0.62; P<0.001), corresponding to a 54% reduction in the risk of death. At the prespecified interim analysis, 200 deaths had occurred.

Trial Design and Patient Population

TAISHAN-302 was a phase III, open-label, randomized superiority trial conducted across 85 clinical sites in China. Eligible patients had SCLC that had progressed or relapsed during or after first-line platinum-based therapy, with ECOG performance status 0-1, measurable disease and adequate organ function. Selected patients with stable asymptomatic brain metastases were eligible.

A total of 451 patients were randomized 1:1 to Tam-Peli 2.0 mg/kg intravenously every three weeks or topotecan查看药品详情 1.2 mg/m² intravenously on days 1-5 every three weeks. The primary endpoint was overall survival, with investigator-assessed progression-free survival and objective response as key secondary endpoints. Crossover between treatment groups was not permitted. In the trial population, 87.1% had received a first-line anti-PD-(L)1 antibody, approximately 34% had a history or presence of brain metastases, almost half had platinum-resistant disease, and patients were not selected on the basis of B7-H3 (搜索)搜索该靶点 expression.

Progression-Free Survival and Response

Median progression-free survival was 7.4 months with Tam-Peli versus 2.8 months with topotecan查看药品详情, a hazard ratio of 0.29 (95% CI, 0.23-0.37; P<0.001), translating into a 71% reduction in the risk of progression or death. Confirmed objective response was observed in 59.1% of patients receiving Tam-Peli compared with 9.7% receiving topotecan. Median duration of response was 6.3 months with Tam-Peli and 7.8 months with topotecan, although the investigators caution that this comparison is difficult to interpret because far fewer patients responded to topotecan.

Among the 434 patients with systemic disease, median overall survival was 12.8 months with Tam-Peli versus 8.8 months with topotecan查看药品详情, an unstratified hazard ratio of 0.49. The investigators reported an overall survival benefit across most prespecified subgroups.

Intracranial Activity

A total of 143 patients had intracranial lesions at baseline. Investigator-assessed intracranial response was 32% with Tam-Peli versus 3% with topotecan查看药品详情, and median intracranial progression-free survival was 6.1 versus 4.2 months. These results are exploratory rather than formally multiplicity-controlled primary outcomes.

Safety Profile

Grade 3 or higher adverse events occurred in 55.4% of patients receiving Tam-Peli versus 77.9% receiving topotecan查看药品详情, and serious adverse events occurred in 38.8% and 43.3%, respectively. Topotecan produced markedly higher rates of severe hematologic toxicity, including grade 3 or higher thrombocytopenia at 54.8% versus 12.5%, anemia at 23.5% versus 10.7%, leukopenia at 32.3% versus 19.2% and neutropenia at 35.5% versus 21.0%.

Tam-Peli still produced substantial myelosuppression, so hematologic surveillance remains necessary. Interstitial lung disease and pneumonitis occurred in 4.9% of patients receiving Tam-Peli compared with 1.4% receiving topotecan查看药品详情. Among the 11 Tam-Peli cases, nine were grade 1-2 and two were grade 3, with no grade 4 or 5 events. All affected patients received systemic glucocorticoids and six permanently discontinued Tam-Peli. The investigators note that this ILD incidence appeared lower than that reported with some other investigational B7-H3 (搜索)搜索该靶点 ADCs, while stating that cross-trial comparisons remain inappropriate.

Mechanism and Target Rationale

B7-H3 (搜索)搜索该靶点, also known as CD276 (搜索)搜索该靶点, is an immune-regulatory member of the B7 family that is highly expressed across several malignancies with more limited expression in many normal tissues. In SCLC, earlier quantitative immunofluorescence studies detected B7-H3 in approximately 65% of tumor specimens, and more recent molecular profiling has demonstrated substantial expression across broader SCLC populations. This makes B7-H3 attractive in SCLC, where classic actionable genomic drivers remain uncommon.

Tam-Peli, previously known as YL201查看药品详情, is a B7-H3 (搜索)搜索该靶点-targeting ADC consisting of a human IgG1 anti-B7-H3 antibody linked through a tripeptide-based linker to YL0010014查看药品详情, a camptothecin-derived topoisomerase I inhibitor payload. The therapeutic concept differs from checkpoint inhibition or DLL3 (搜索)搜索该靶点-directed T-cell engagement: B7-H3 serves as the tumor-associated delivery address, allowing a potent cytotoxic payload to be transported preferentially into B7-H3-expressing cancer cells.

Positioning Relative to Tarlatamab

The TAISHAN-302 investigators explicitly discuss how Tam-Peli should eventually be positioned relative to tarlatamab查看药品详情, the DLL3 (搜索)搜索该靶点×CD3 bispecific T-cell engager that has also demonstrated an overall survival benefit in previously treated SCLC. In DeLLphi-304, median overall survival was 13.6 months with tarlatamab versus 8.3 months with chemotherapy, compared with 13.3 months versus 9.4 months in TAISHAN-302. The investigators state these figures should not be used for indirect efficacy ranking because patient populations, control regimens, subsequent therapies, geography and study designs differed.

The two therapies use fundamentally different biology, with tarlatamab查看药品详情 relying on DLL3 (搜索)搜索该靶点×CD3 T-cell engagement and Tam-Peli on B7-H3 (搜索)搜索该靶点-directed delivery of a topoisomerase I payload. Their toxicity profiles also differ, with tarlatamab associated predominantly with cytokine-release syndrome and immune effector cell-associated neurotoxicity, while Tam-Peli is characterized more by myelosuppression and ADC-associated pulmonary toxicity.

Biomarker Questions and Limitations

Because treatment did not require prospective B7-H3 (搜索)搜索该靶点 biomarker selection, an open question for future development is whether the level, distribution or heterogeneity of B7-H3 expression predicts response. The trial establishes B7-H3 as a therapeutic entry point but does not establish B7-H3 expression as a validated predictive biomarker.

The authors identify several limitations. TAISHAN-302 was open label, which can influence treatment management and adverse-event reporting, and progression-free survival and response were assessed by investigators rather than blinded independent central review, although the primary endpoint of overall survival is not affected by radiographic interpretation. Enrollment occurred entirely in China, the study included a relatively high proportion of never-smokers and was predominantly male, and the authors state that validation in more geographically and demographically diverse populations is required before the findings can be fully generalized worldwide. Median follow-up was still relatively short at approximately nine months at this prespecified interim analysis.

Development Moving Into First Line

The authors report that a phase III trial evaluating tambotatug pelitecan (搜索)搜索该药品 combined with a PD-1 (搜索)搜索该靶点 inhibitor as first-line therapy for SCLC is ongoing. The TAISHAN-302 data position B7-H3 (搜索)搜索该靶点-directed ADC therapy as a new component of the relapsed SCLC landscape, alongside DLL3 (搜索)搜索该靶点-directed T-cell engagement, and raise sequencing as the next major research question.