Trial Overview
- Design & Participants
- Global, open-label, randomized Phase III study (NCT05740566)
- 509 patients with extensive-stage SCLC who progressed after first-line platinum-based chemotherapy (with or without PD-1/PD-L1 therapy)
- Randomized 1:1 to:
- Tarlatamab (Imdelltra): a bispecific T-cell engager targeting DLL3 and CD3
- Physician’s choice chemotherapy: Topotecan, lurbinectedin, or amrubicin
- ~17% of participants had brain metastases; DLL3 expression prevalence was >90% across both arms
Efficacy Results
- Overall Survival (OS)
- Median OS: 13.6 months (tarlatamab) vs. 8.3 months (chemotherapy)
- Hazard Ratio (HR) for death: 0.60 (95% CI: 0.47–0.77; P < 0.001)
- 6-month OS rates: 76% vs. 62%; 12-month OS: 53% vs. 37%
- Progression-Free Survival (PFS)
- Median PFS: ~4.2 months (tarlatamab) vs. ~3.2–3.7 months (chemotherapy)
- HR for progression: ~0.71–0.72 (P < 0.001)
- Response Rates
- Overall response rate (ORR): 35% vs. 20%
- Median duration of response: 6.9 months vs. 5.5 months
- Disease control rate (DCR): 68% vs. 64%
Safety & Patient Experience
- Adverse Events (AEs)
- Grade ≥3 AEs: 27% (tarlatamab) vs. 62% (chemotherapy)
- Discontinuation due to AEs: 3% vs. 6%
- Unique Safety Considerations
- Cytokine release syndrome (CRS) reported in 56% of patients (mostly grade 1–2 and manageable)
- Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in ~6%
- One treatment-related death in the tarlatamab arm (due to ICANS); four in chemotherapy arm (various causes)
- Symptom Relief
- Tarlatamab showed significant improvements in patient-reported outcomes:
- Dyspnea scores improved
- Higher rates of cough and chest pain relief compared to chemotherapy
- Tarlatamab showed significant improvements in patient-reported outcomes:
Clinical Impact
- Established new standard of care:
- DeLLphi-304 marks the first randomized evidence in small-cell lung cancer where a bispecific T-cell engager demonstrated superior OS over chemotherapy in the second-line setting ILCN.org (ILCN/WCLC)Daily Reporter
- Regulatory Support:
- The FDA granted accelerated approval to tarlatamab (Imdelltra®) in May 2024 for extensive-stage SCLC post–platinum chemotherapy, based on earlier DeLLphi-301 Phase II data; DeLLphi-304 provides confirmatory evidence