The B7-H3–directed antibody-drug conjugate (ADC) tambotatug pelitecan (tam-peli; YL201) significantly improved overall survival (OS) versus topotecan in patients with small cell lung cancer (SCLC) that progressed after 1 prior line of platinum-based therapy, according to interim analysis data from the phase 3 TAISHAN-302 trial (NCT06612151) presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).1
At a data cutoff of May 20, 2026, the median OS was 13.3 months (95% CI, 12.1 - not estimable [NE]) with tam-peli (n = 225) vs 9.4 months (95% CI, 7.7 - 10.5) with topotecan (n = 226), for a stratified HR of 0.46 (95% CI, 0.35 - 0.62; P <.0001). OS events had occurred in 33.8% and 54.9% of patients, respectively, and median follow-up for OS was 9.2 and 9.5 months.
The investigator-assessed median progression-free survival (PFS) was 7.4 months (95% CI, 6.1 - 7.6) with tam-peli versus 2.8 months (95% CI, 1.8 - 3.0) with topotecan (HR, 0.29; 95% CI, 0.23 - 0.37; P <.0001), and the confirmed objective response rate (ORR) was 59.1% (95% CI, 52.4%-65.6%) vs 9.7% (95% CI, 6.2%-14.4%), respectively (P <.0001).
Investigators reported that the OS benefit was consistent across all prespecified subgroups, including patients with baseline brain metastases and those with a chemotherapy-free interval of less than 90 days.1,2
"TAISHAN-302 is among the first phase 3 studies of an antibody-drug conjugate to demonstrate statistically significant and clinically meaningful improvements in overall survival, progression-free survival and objective response rate compared with topotecan in relapsed small-cell lung cancer," lead study author Li Zhang, MD, professor of medical oncology at Sun Yat-sen University Cancer Center, said in a news release issued by the IASLC.2 "Together with a generally favorable and manageable safety profile, these results support Tam-Peli as a potential new standard-of-care option for second-line SCLC and may reshape the treatment landscape for this challenging disease."
Rationale for TAISHAN-302
Topotecan has long served as a standard second-line option for relapsed SCLC, but its survival benefit is modest, and outcomes after first-line chemoimmunotherapy remain poor. Tam-peli comprises a fully human IgG1 antibody targeting B7-H3 conjugated to a topoisomerase I inhibitor payload (YL0010014) via a tumor microenvironment–activable cleavable linker, at a drug-to-antibody ratio of 8; investigators noted that the payload is 5 - 10 times more potent than deruxtecan. The agent demonstrated activity in relapsed SCLC in preclinical and phase 1/2 studies.1
B7-H3 has become an active target in SCLC through other findings presented at WCLC 2026. First data from the phase 1b/2 BNT324-01 trial (NCT06892548) showed that the B7H3-directed ADC elfetabart drozuntecan plus the PD-L1 x VEGF-A bispecific antibody pumitamig generated a 70.4% ORR across lines of therapy in SCLC.3 In the DLL3-directed T-cell engager class, the randomized phase 2 DeLLphi-309 trial (NCT06745323) reported ORRs of 27% to 40% with standard and extended-interval tarlatamab-dlle (Imdelltra) regimens in SCLC after platinum-based chemotherapy.4
TAISHAN-302 Trial Design
The multicenter, open-label study was conducted at 85 sites in China and enrolled patients with histologically or cytologically confirmed SCLC that progressed after 1 prior line of platinum-based therapy, at least 1 measurable lesion, and an ECOG performance status of 0 or 1.
Patients were randomly assigned 1:1 to intravenous tam-peli at 2.0 mg/kg on day 1 of each 3-week cycle, to a maximum dose of 200 mg, or topotecan at 1.2 mg/m2 on days 1 - 5 of each 3-week cycle per the Chinese prescribing information. Randomization was stratified by disease stage at enrollment (local vs systemic), brain metastasis (yes vs no), and chemotherapy-free interval (<90 vs ≥90 days). Treatment continued until disease progression or intolerable toxicity, and crossover was not permitted.1
The primary end point was OS; key secondary end points were investigator-assessed PFS and ORR, tested hierarchically after OS. Other secondary end points included disease control rate (DCR), duration of response (DOR), time to response, safety, pharmacokinetics, and immunogenicity, and intracranial efficacy was an exploratory end point.
The design called for 285 OS events at the final analysis, with 1 interim analysis at 190 events at a one-sided α of .006; 200 OS events had occurred at the data cutoff.1
Baseline characteristics were balanced. Median age was 62 years in both arms, 81.3% and 84.5% of patients were male, and 82.7% and 88.1% had an ECOG performance status of 1 in the tam-peli and topotecan arms, respectively. Prior immunotherapy had been received by 86.2% and 88.1% of patients, 48.9% and 48.7% had a chemotherapy-free interval of less than 90 days, 34.7% and 34.1% had brain metastases, and 32.0% and 35.4% had liver metastases.
At the data cutoff, 71 patients remained on tam-peli vs 8 on topotecan; median duration of exposure was 31.1 weeks (range, 3-72.9) vs 10.1 weeks (range, 3-70.4).1
TAISHAN-302 Highlights
- Median OS was 13.3 months vs 9.4 months (HR, 0.46; 95% CI, 0.35 - 0.62), meeting the primary end point at the interim analysis.
- Median PFS was 7.4 months vs 2.8 months (HR, 0.29), and confirmed ORR was 59.1% versus 9.7%.
- In patients with brain metastases, intracranial ORR was 32.4% versus 2.9% and median intracranial PFS was 6.1 vs 4.2 months (HR, 0.43).
- Grade 3 or higher TRAEs occurred in 46.4% versus 74.7% of patients; ILD/pneumonitis occurred in 4.9% vs 1.4%, with no grade 4 or 5 events.
Additional Efficacy Data
Best overall response with tam-peli comprised partial responses in 59.1% of patients, stable disease in 32.0%, and progressive disease in 6.7%. With topotecan, the rates were 9.7%, 41.2%, and 35.4%, respectively, and no complete responses occurred in either arm.
The DCR was 91.1% (95% CI, 86.6 - 94.5) versus 50.9% (95% CI, 44.2 - 57.6). Median DOR was 6.3 months (95% CI, 6.0 - 8.0) with tam-peli versus 7.8 months (95% CI, 3.3 - 9.9) with topotecan, and median time to response was 1.5 months (range, 1.1 - 4.5) versuss 2.6 months (range, 1.4 - 4.8). PFS events had occurred in 59.6% and 79.2% of patients, respectively, at a median PFS follow-up of 7.8 and 8.4 months; investigators reported a consistent PFS benefit across all subgroups.1
Among patients with baseline brain metastases (n = 74 vs n = 69), intracranial efficacy assessed by investigators favored tam-peli. Median intracranial PFS was 6.1 months (95% CI, 5.7 - 7.8) versus 4.2 months (95% CI, 2.8 - 5.6; HR, 0.43; 95% CI, 0.27 - 0.68; nominal P = .0002), the intracranial confirmed ORR was 32.4% (95% CI, 22.0 - 44.3%) versuss 2.9% (95% CI, 0.4 - 10.1; nominal P< .0001), and the intracranial DCR was 90.5% (95% CI, 81.5 - 96.1) versus 59.4% (95% CI, 46.9 - 71.1; nominal P < .0001).
Safety Profile of Tam-Peli vs Topotecan
In the safety population (n = 224 vs n = 217), any-grade treatment-related adverse events (TRAEs) occurred in 98.7% of patients receiving tam-peli and 99.5% receiving topotecan. Grade ≥3 TRAEs occurred in 46.4% versus 74.7%, serious TRAEs in 25.9% versus 36.4%, TRAEs leading to dose interruption in 34.8% versus 36.9%, TRAEs leading to dose reduction in 25.9% versus 36.9%, and TRAEs leading to discontinuation in 5.8% versus 2.8%.
No treatment-related deaths occurred with tam-peli; 1 (0.5%) occurred with topotecan. The most common grade ≥3 TRAEs in both arms were hematologic, with lower incidence in the tam-peli arm.
Treatment-emergent interstitial lung disease (ILD)/pneumonitis occurred in 4.9% of patients receiving tam-peli versuss 1.4% receiving topotecan; grade 3 events occurred in 0.9% of patients in each arm, and no grade 4 or 5 events were reported. Investigators concluded that the safety profile was generally favorable and manageable with no new or unexpected signals, and that the results establish tam-peli as a potential new standard of care for relapsed SCLC.1
References
- Zhang L, Zhao Y, Liu H, et al. Tam-Peli, an anti-B7-H3 antibody-drug conjugate, versus topotecan in relapsed small cell lung cancer (SCLC): a randomized, open-label, phase 3 study (TAISHAN-302). Presented at: International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract PL02.03.
- Phase III TAISHAN-302 trial shows Tam-Peli significantly improves survival in relapsed small-cell lung cancer. News release. International Association for the Study of Lung Cancer. September 13, 2026. Accessed September 13, 2026.
- Pumitamig Plus Elfetabart Drozuntecan Elicits 70% ORR Across Lines of Therapy in SCLC. OncLive. Published September 12, 2026. Accessed September 13, 2026. https://www.onclive.com/view/pumitamig-elfetabart-drozuntecan-orr-sclc
- Extended-Interval Tarlatamab Yields Comparable Exposure, Survival to Q2W Dose in Previously Treated SCLC. OncLive. Published September 12, 2026. Accessed September 13, 2026. https://www.onclive.com/view/extended-interval-tarlatamab-exposure-survival-q2w-dose-previously-treated-sclc
