The European Commission has approved Amgen’s IMDYLLTRA® (tarlatamab), the first T‑cell engager for extensive‑stage small cell lung cancer in Europe, delivering a 40% survival benefit over chemotherapy in the Phase 3 DeLLphi‑304 trial.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
The European Commission has granted marketing authorization for IMDYLLTRA® (tarlatamab) as monotherapy for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has progressed following platinum-based chemotherapy.
The approval applies across all 27 EU member states and the European Economic Area, marking the first T-cell engager authorized for small cell lung cancer in Europe.
Phase 3 Trial Delivers Significant Survival Benefit
Approval was supported by the pivotal Phase 3 DeLLphi-304 trial (NCT05740566), which enrolled 509 patients with relapsed ES-SCLC. Tarlatamab reduced the risk of death by 40% compared with chemotherapy, extending median overall survival to 13.6 months versus 8.3 months (HR 0.60; 95% CI: 0.47–0.77; p<0.001). Progression-free survival also favored tarlatamab, while patient-reported outcomes indicated improved quality of life relative to standard regimens.
Mechanism of Action
Tarlatamab is a first-in-class bispecific T-cell engager targeting DLL3, which is expressed on up to 96% of SCLC tumors, and CD3 on T cells. By bridging T cells to tumor cells, the therapy triggers targeted cancer cell destruction while largely sparing healthy tissues, addressing a long-standing therapeutic gap in SCLC.
Comparator Context
Patients in the control arm received regionally accepted chemotherapy, including topotecan, lurbinectedin, or amrubicin. These treatments have historically delivered limited benefit, highlighting the clinical significance of tarlatamab’s survival advantage in a disease where relapse commonly occurs within months of first-line therapy.
Safety Profile Remains Consistent
The safety profile was consistent with earlier studies. The most common adverse events included cytokine release syndrome (CRS), pyrexia, decreased appetite, dysgeusia, constipation, anemia, fatigue, and nausea. CRS and pyrexia were the most frequent serious adverse reactions and occurred predominantly after the first two doses.
Most CRS events were manageable. Current prescribing guidance recommends monitoring patients for 6 to 8 hours following infusion on Cycle 1 Day 1 and Cycle 1 Day 8 to ensure early detection and management of treatment-related reactions.
Future Development
Amgen continues to expand the tarlatamab clinical program through multiple DeLLphi studies evaluating the therapy in earlier lines of treatment, maintenance settings, and combination regimens. Ongoing Phase 1, 2, and 3 trials are assessing whether the DLL3-targeted T-cell engager can improve outcomes across broader SCLC populations and move into earlier stages of disease.
Transforming Second-Line Therapy
Small cell lung cancer remains one of the most aggressive solid tumors, with most patients experiencing rapid relapse after first-line treatment and few effective options available thereafter. By delivering the first Phase 3 survival benefit over chemotherapy in this setting, tarlatamab introduces a new treatment class to the European market and has the potential to reshape second-line treatment for patients with relapsed ES-SCLC.
Reference
About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.