Amgen’s Imdylltra becomes first EU approved TCE for SCLC

Edited by Robert McTiernan··3 min read

The European Commission has granted marketing authorization for Imdylltra (tarlatamab), making Amgen (Nasdaq: AMGN) the first company to win approval for a T-cell engager therapy in small cell lung cancer in Europe. The approved indication covers adults with extensive-stage disease who have progressed on or after first-line platinum-based chemotherapy.

The European authorization follows tarlatamab’s earlier regulatory success in the US, where the DLL3-targeting bispecific T-cell engager received FDA accelerated approval in May 2024 based on results from the Phase II DeLLphi-301 study. The agency subsequently converted that decision to full approval in November 2025 after the Phase III DeLLphi-304 trial confirmed a significant overall survival benefit over standard chemotherapy, making tarlatamab the first T-cell engager approved for a solid tumor.

The Amgen Imdylltra approval rests on results from the DeLLphi-304 trial (NCT05740566), a global Phase III, randomized, open-label study that enrolled 509 patients with extensive-stage small cell lung cancer who had progressed following at least one platinum-based regimen. The trial’s primary endpoint was overall survival (OS), and the DeLLphi-304 trial results were unambiguous: tarlatamab reduced the risk of death by 40% compared to investigator’s-choice chemotherapy, extending median OS from 8.3 months to 13.6 months (hazard ratio 0.60; 95% CI: 0.47, 0.77; P < 0.001).

Those figures are significant in a disease where second-line survival is typically measured in single-digit months. The comparator arms reflected current practice — topotecan in most countries, lurbinectedin in the US, Canada, Australia, Singapore, and South Korea, and amrubicin in Japan.

Tarlatamab is engineered as a bispecific T-cell engager (TCE) that binds DLL3, a protein expressed in 96% of SCLC tumors, and CD3 on T cells, pulling cytotoxic lymphocytes into proximity with tumor cells and triggering a targeted killing response. The DLL3 target is biologically well-suited to SCLC. Unlike many solid tumors where target expression is heterogeneous, DLL3 is broadly and consistently expressed across the SCLC population, which removes the need for prospective biomarker selection in the approved indication. No DLL3 expression threshold is required for patient eligibility under the EU label.

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The most clinically significant adverse reaction associated with Imdylltra is cytokine release syndrome (CRS), which occurred in 56.7% of patients in pooled safety data from 473 SCLC patients. The majority of CRS events were low-grade — 39.3% grade 1 and 15.4% grade 2 — though serious CRS was reported in 19.7% of patients, and fatal cases have been documented in the post-marketing setting.

To reduce CRS risk, the EU label specifies a step-up dosing schedule: an initial 1 mg dose on day 1, followed by 10 mg on days 8 and 15, then every two weeks thereafter. Patients must be monitored for six to eight hours following the first two infusions in an appropriate healthcare setting and are required to remain within proximity of a facility for 24 hours after each of those doses.

Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 4.7% of patients, with a median onset of nine days from first dose and a median resolution time of four days. Neutropenia, infections, hepatotoxicity, and hypersensitivity reactions are also documented risks. The requirement for supervised infusion and post-dose monitoring reflects a safety profile that, while manageable, demands institutional infrastructure.

The EC authorization covers second-line and later disease, but Amgen is also evaluating tarlatamab in earlier-stage settings. Ongoing Phase III studies are testing the therapy in first-line ES-SCLC and following chemoradiotherapy in limited-stage disease, while additional studies are exploring alternative dosing approaches and combination regimens.

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