FDA Grants Full Approval to Tarlatamab for Second-Line Treatment of Small Cell Lung Cancer
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Tarlatamab Receives Full Approval in SCLC
For extensive-stage small cell lung cancer (ES-SCLC) progressing after platinum-based chemotherapy, the FDA granted Tarlatamab (Imdelltra) traditional (full) approval. The DeLLphi-304 trial demonstrated that, compared with standard chemotherapy, it reduced mortality risk by 40% .
On 19 November 2025, the US Food and Drug Administration (FDA) granted, for adults with extensive-stage small cell lung cancer ((ES-SCLC) progressing during or after platinum-based chemotherapy, tarlatamab-dlle (Imdelltra, Amgen Inc.) traditional approval (full approval). Tarlatamab-dlle had received accelerated approval for this indication in 2024.
A Challenging Target: SCLC
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers but is the most aggressive type. It grows rapidly and metastasizes early. Most patients are diagnosed at the ‘extensive stage’, and options after platinum-based chemotherapy are limited (Topotecan, etc.).
Tarlatamab is one of the most important innovations in this field to offer a survival advantage after many years.
🔬 How It Works: BiTE Technology
Tarlatamab is a DLL3 (Delta-like ligand 3) -targeted bispecific T-cell engager (BiTE).
- One arm: Binds to DLL3 protein on the cancer cell surface (present in 85–96% of SCLC cells).
- The other arm: Binds to CD3 on the patient’s own T cell.
It thereby draws the T cell right next to the cancer cell, allowing the immune system to destroy the tumor.
The Evidence: DeLLphi-304
Efficacy was evaluated in a randomized, open-label study enrolling 509 patients whose disease progressed after platinum-based chemotherapy: DeLLphi-304 (NCT05740566) . Patients were assigned 1:1 to receive Tarlatamab or standard care (Topotecan, Lurbinectedin or Amrubicin).
Overall Survival (OS) Results
Average survival of patients in the Tarlatamab arm (8.3 months in the standard arm).
Compared with standard chemotherapy, Tarlatamab reduced mortality risk by 40% (p<0.001).
Time without disease progression was statistically longer than in the standard arm (3.2 months).
🏃 Quality of Life: The trial also showed that patients receiving Tarlatamab had, at week 18, shortness of breath (dyspnea) symptoms improve significantly compared with standard care.
Safety and Administration
⚠️ Boxed Warning
The prescribing information contains the strongest warning for the following:
- Cytokine Release Syndrome (CRS): May be life-threatening.
- Neurological Toxicity: Including immune effector cell-associated neurotoxicity syndrome (ICANS).
💊 Recommended Dosage (Step-Up Dosing)
The dose is increased gradually to reduce the risk of CRS:
- Cycle 1, Day 1: 1 mg
- Cycle 1, Days 8 and 15: 10 mg
- Thereafter: 10 mg every 2 weeks until disease progression.
🌍 Project Orbis
This review was conducted concurrently with regulatory agencies in Australia (TGA), Canada (HC) and the United Kingdom (MHRA) through Project Orbis, the international collaboration initiative of the FDA Oncology Center of Excellence.
- FDA. FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. 19 November 2025. [FDA Announcement]
- ClinicalTrials.gov. A Study of Tarlatamab in Patients With Small Cell Lung Cancer (DeLLphi-304). NCT05740566. [Clinical Trial Details]
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