EMA Backs Amgen's Tarlatamab as First-in-Class BiTE Therapy for Advanced Small Cell Lung Cancer

Key Takeaways

• The EMA CHMP adopted a positive opinion for tarlatamab Imdylltra on March 26, 2026, with the European Commission expected to issue final marketing authorization within 67 days.
• Phase 3 clinical data demonstrated a 40% reduction in the risk of death compared to standard care, with median overall survival of 13.6 months versus 8.3 months.
• Imdylltra targets DLL3-expressed tumor cells and CD3 on T-cells, representing the first BiTE therapy approved for a solid tumor indication.
• The therapy carries a boxed warning for cytokine release syndrome (CRS) and requires specialized monitoring protocols.
• Following FDA accelerated approval in May 2024, EU approval would mark the second major regulatory validation for Amgen's BiTE platform in oncology.

What Did the EMA Committee Recommend?

The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion on March 26, 2026. The applicant, Amgen Europe B.V., submitted data from the Phase 3 DeLLphi-304 trial. This trial supported the indication for adult patients with ES-SCLC who had progressed after first-line platinum-based chemotherapy.

This positive opinion represents the penultimate step before final marketing authorization in the European Union. The European Commission typically adopts CHMP recommendations within 67 days, suggesting EU market access could be achieved by mid-2026.

How Does Tarlatamab Work?

Tarlatamab is a bispecific T-cell engager (BiTE). It targets DLL3 on small cell lung cancer cells and CD3 on T-cells. This mechanism redirects the immune system to attack tumor cells. DLL3 is highly expressed in about 85% of SCLC tumors.

The BiTE platform represents a novel approach in solid tumor immunotherapy, as previous BiTE therapies were primarily approved for hematologic malignancies. Tarlatamab's approval would mark the first validated application of this technology in a solid tumor indication.

What Clinical Evidence Supported the Opinion?

The EMA positive opinion was based on data from the Phase 3 DeLLphi-304 trial, which demonstrated statistically significant improvements in overall survival. According to the EMA's clinical assessment, patients receiving tarlatamab experienced a 40% reduction in the risk of death compared to standard chemotherapy.

Key efficacy results included:

• Median overall survival: 13.6 months (tarlatamab) versus 8.3 months (standard care)
• Statistically significant improvement in survival outcomes
• Consistent benefit across patient subgroups

Additionally, earlier Phase 2 data from the DeLLphi-301 trial (NCT05060016) showed an overall response rate of 40% with a median duration of response of 9.7 months in heavily pretreated patients, which supported the FDA accelerated approval in May 2024.

What Are the Safety Considerations?

Tarlatamab carries important safety risks. Patients need careful monitoring. The most common side effects include:

• Cytokine release syndrome (CRS) — can be severe and requires immediate intervention
• Decreased appetite
• Fever and pyrexia
• Immune-related reactions

The therapy must be given in settings that can manage CRS and neurological side effects. Providers use step-up dosing and monitoring protocols.

How Does This Compare to Current Treatment Options?

Treatment options for extensive-stage small cell lung cancer have remained largely unchanged for decades, with most patients seeing disease progression within months of initial platinum-based chemotherapy. Current second-line choices include:

Current ES-SCLC Second-Line Treatment Options

Therapy	Mechanism	Median OS (months)
Lurbinectedin	RNA polymerase II inhibitor	~8-9
Topotecan	Topoisomerase I inhibitor	~6-8
Tarlatamab (Imdylltra)	BiTE anti-DLL3/CD3	13.6*

*From Phase 3 DeLLphi-304 trial versus standard care.

Previous attempts to develop targeted therapies for SCLC, including the DLL3-targeting antibody-drug conjugate Rova-T, failed in late-stage development due to efficacy and toxicity concerns, highlighting the significance of tarlatamab's success.

What Happens Next in the Regulatory Process?

Following the CHMP positive opinion, the formal regulatory pathway proceeds as follows:

1. European Commission review and decision (typically within 67 days)
2. Publication of the marketing authorization in the Official Journal of the European Union
3. National-level pricing and reimbursement negotiations in EU member states
4. Healthcare system readiness planning for administration and monitoring infrastructure

The European approval would complement existing authorizations and expand patient access beyond the United States, where the therapy is already commercially available following FDA accelerated approval.

Frequently Asked Questions

Primary Sources

• EMA CHMP Summary of Positive Opinion for Imdylltra (March 26, 2026): ema.europa.eu
• EMA News: New treatment for relapsed extensive-stage small cell lung cancer: ema.europa.eu
• FDA Approval Letter for Tarlatamab (May 16, 2024): accessdata.fda.gov
• FDA Drug Approval Announcement: fda.gov
• ClinicalTrials.gov: DeLLphi-301 Study (NCT05060016): clinicaltrials.gov

Related profiles

• tarlatamab
• Amgen
• EMA
• small cell lung cancer

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