Background
Phase 3, multicenter, open-label, randomized (1:1), 85 sites in China. N=451. SCLC progressed/relapsed during or after 1L platinum-based therapy; ECOG 0–1; stable asymptomatic brain mets allowed. ~34% brain mets, ~48% platinum-resistant, 87% prior PD-(L)1. No B7-H3 selection. Tambotatug pelitecan (Tam-Peli, YL201) = anti-B7-H3 IgG1 ADC with tripeptide linker and camptothecin-derived TOP1 inhibitor payload (YL0010014). No crossover.
Results
Interventions and follow up: Arm A: Tambotatug pelitecan 2.0 mg/kg IV q3w (n=225)
Arm B: Topotecan 1.2 mg/m² IV D1–5 q3w (n=226)
Primary endpoint: OS
Key secondary: PFS, ORR (investigator-assessed)
mFollow up: 9.4 mo (prespecified interim analysis, 200 deaths)
Results: OS: 13.3 vs 9.4 mo, HR 0.46 (95% CI 0.35–0.62), P<.001
PFS: 7.4 vs 2.8 mo, HR 0.29 (95% CI 0.23–0.37), P<.001
ORR: 59.1% vs 9.7%, P<.001
mDOR: 6.3 vs 7.8 mo
Intracranial ORR (n=143, exploratory): 32% vs 3%; intracranial PFS 6.1 vs 4.2 mo
OS benefit consistent across prespecified subgroups
Arm B: Topotecan 1.2 mg/m² IV D1–5 q3w (n=226)
Primary endpoint: OS
Key secondary: PFS, ORR (investigator-assessed)
mFollow up: 9.4 mo (prespecified interim analysis, 200 deaths)
Results: OS: 13.3 vs 9.4 mo, HR 0.46 (95% CI 0.35–0.62), P<.001
PFS: 7.4 vs 2.8 mo, HR 0.29 (95% CI 0.23–0.37), P<.001
ORR: 59.1% vs 9.7%, P<.001
mDOR: 6.3 vs 7.8 mo
Intracranial ORR (n=143, exploratory): 32% vs 3%; intracranial PFS 6.1 vs 4.2 mo
OS benefit consistent across prespecified subgroups
Adverse events
Grade ≥3 (any): 55.4% vs 77.9%
Serious AEs: 38.8% vs 43.3%
Hematologic G≥3: thrombocytopenia 12.5% vs 54.8%, neutropenia 21.0% vs 35.5%, leukopenia 19.2% vs 32.3%, anemia 10.7% vs 23.5%
ILD/pneumonitis: 4.9% vs 1.4% (Tam-Peli: 9 G1–2, 2 G3, no G4–5; 6 discontinued)
Serious AEs: 38.8% vs 43.3%
Hematologic G≥3: thrombocytopenia 12.5% vs 54.8%, neutropenia 21.0% vs 35.5%, leukopenia 19.2% vs 32.3%, anemia 10.7% vs 23.5%
ILD/pneumonitis: 4.9% vs 1.4% (Tam-Peli: 9 G1–2, 2 G3, no G4–5; 6 discontinued)
Conclusions
In relapsed SCLC after platinum, the B7-H3 ADC tambotatug pelitecan improved OS by ~4 mo (HR 0.46), PFS (HR 0.29) and ORR (59% vs 10%) over topotecan, with fewer grade ≥3 AEs. Second phase 3 OS win in 2L SCLC after DeLLphi-304 (tarlatamab), establishing B7-H3 as a validated target and a mechanistically distinct chemo-free alternative to topotecan.
Key Limitations
Open-label; PFS/ORR investigator-assessed (no BICR). Interim analysis with short follow-up (9.4 mo). Enrolled entirely in China (predominantly male, high proportion of never-smokers) — generalizability to Western populations unproven. Topotecan comparator (not lurbinectedin or tarlatamab). No biomarker (B7-H3) selection or predictive analysis. Sequencing vs tarlatamab unknown.
Clinical Context
Prior 2L SCLC standard: topotecan or lurbinectedin; tarlatamab (DeLLphi-304: OS 13.6 vs 8.3 mo) is the NCCN-preferred 2L option in the US. Tam-Peli offers similar OS magnitude via a different mechanism (ADC vs DLL3 T-cell engager) and toxicity profile (myelosuppression/ILD vs CRS/ICANS). Not yet FDA/EMA approved as of Sep 2026 (MediLink/Roche-partnered); NMPA filing expected. Phase 3 of Tam-Peli + PD-1 inhibitor in 1L SCLC ongoing. Other B7-H3 ADCs (ifinatamab deruxtecan, IDeate-Lung02) in phase 3.