Tarlatamab-dlle Approved for Relapsed Extensive-Stage Small Cell Lung Cancer
Expert Perspectives
By Lyn Brook
Published
The FDA granted traditional approval to the DLL3-directed bispecific T-cell engager tarlatamab-dlle (Imdelltra®, Amgen) for adults with extensive-stage small cell lung cancer (ES‑SCLC) with disease progression on or after platinum-based chemotherapy.
Tarlatamab-dlle previously received accelerated approval for this indication in 2024; the current decision converts this to full approval based on confirmatory overall survival (OS) benefit.
Why This Approval Matters
ES-SCLC is an aggressive malignancy characterized by high initial chemosensitivity but rapid development of resistance and frequent, early relapse. After progression on platinum-based chemotherapy, with or without prior anti–PD-(L)1 therapy, treatment options are limited and outcomes are poor. The traditional approval of tarlatamab-dlle is supported by a randomized phase 3 trial demonstrating a clinically meaningful and statistically significant OS advantage over standard chemotherapy options. This establishes tarlatamab-dlle as an important new standard of care in the post-platinum relapsed ES-SCLC setting.
Breaking Down DeLLphi-304
Efficacy was evaluated in DeLLphi-304 (NCT05740566), a phase 3, multicenter, randomized, open-label trial in patients with SCLC and disease progression after platinum-based chemotherapy, with or without prior anti–PD-(L)1 therapy. A total of 509 patients were randomized 1:1 to receive either tarlatamab-dlle or investigator’s choice of standard of care (SOC) chemotherapy (topotecan, lurbinectedin, or amrubicin) until disease progression or unacceptable toxicity.
The key primary efficacy end point was OS; key secondary end points included progression-free survival (PFS) by investigator assessment per RECIST v1.1 and selected patient-reported outcomes (PROs). Results were as follows:
- Median OS: 13.6 months with tarlatamab-dlle vs 8.3 months with SOC chemotherapy
- Median PFS: 4.2 months in the tarlatamab-dlle arm vs 3.2 months in the SOC arm
- The trial showed a statistically significant improvement in dyspnea at Week 18 for patients treated with tarlatamab-dlle compared with SOC, supporting symptomatic benefit in addition to survival gains
Managing Adverse Events
The prescribing information includes a Boxed Warning for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS). Additional warnings and precautions address cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity.
Dosing and Administration
The recommended maintenance dosing schedule of tarlatamab-dlle should be administered as follows: 1 mg on Cycle 1, Day 1; 10 mg on Days 8 and 15; then 10 mg every two weeks until disease progression or unacceptable toxicity.