On November 19, 2025, the U.S. Food and Drug Administration (FDA) granted traditional approval to tarlatamab-dlle (Imdelltra, Amgen) for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed after platinum-based chemotherapy.
On the same day, the FDA granted accelerated approval to sevabertinib (Hyrnuo, Bayer) for adults with locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) harboring HER2 (ERBB2) TKD activating mutations.
Tarlatamab-dlle Full Approval: A New Standard for SCLC
Tarlatamab is a DLL3-targeted CD3×DLL3 bispecific T-cell engager (TCE). Its full approval is based on results from the DeLLphi-304 trial (NCT05740566) enrolling 509 patients randomized to tarlatamab or standard-of-care chemotherapy.
- Median OS: 13.6 months vs 8.3 months (HR=0.60; p<0.001)
- PFS: 4.2 vs 3.2 months (HR=0.72)
- PROs: Statistically significant improvement in dyspnea at week 18
Boxed warnings include cytokine release syndrome (CRS) and ICANS. Dosing: 1 mg on C1D1 → 10 mg on D8, D15 → then 10 mg every 2 weeks.
Sevabertinib Accelerated Approval: Targeting HER2 TKD Mutations
Sevabertinib is a selective inhibitor for HER2 TKD activating mutations. Efficacy was evaluated in the SOHO-01 trial (NCT05099172).
HER2-TKD mutated, prior therapy (ADC-naïve), n=70:
- ORR: 71%
- Median DOR: 9.2 months
- 54% with DOR ≥6 months
HER2 ADC–pretreated, n=52:
- ORR: 38%
- Median DOR: 7.0 months
Warnings include diarrhea, hepatotoxicity, ILD/pneumonitis, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.
Dosing: 20 mg orally twice daily with food.
Clinical Significance
Tarlatamab’s full approval marks the first DLL3-targeted TCE to demonstrate a clear overall survival benefit in ES-SCLC — a transformational milestone for this historically difficult-to-treat cancer.
Sevabertinib expands options for HER2-mutated NSCLC, particularly notable for ADC-pretreated patients who still demonstrate meaningful response.
Both approvals were conducted within Project Orbis, reflecting global collaboration to accelerate treatments for high-unmet-need cancers.
This article was produced by the Morningglorysciences Editorial Team.
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