Tarlatamab Receives EU Approval in Extensive-Stage Small Cell Lung Cancer

The European Commission has granted marketing authorization to tarlatamab-dlle (Imdylltra) as a treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) who have progressed on or after frontline care with platinum-containing chemotherapy, according to a press release from the developer, Amgen.¹

Supporting data for the regulatory decision came from the phase 3 DeLLphi-304 trial (NCT05740566), which assessed the safety and efficacy of tarlatamab vs standard chemotherapy among patients with SCLC and progression on or after platinum-based chemotherapy.² Previous data revealed a median overall survival (OS) of 13.6 months (11.1-not reached) with tarlatamab vs 8.3 months (95% CI, 7.0-10.2) with chemotherapy, reflecting a 40% reduction in the risk of death (HR, 0.60; 95% CI, 0.47-0.77; P <.001). Additionally, the median progression-free survival (PFS) was 4.2 months (95% CI, 3.4-4.5) and 3.7 months (95% CI, 2.9-4.2) in each respective arm. The confirmed objective response rate (ORR) was 35% (95% CI, 29%-41%) vs 20% (95% CI, 16%-26%), respectively (risk ratio, 1.73; 95% CI, 1.29-2.33).

The safety profile of tarlatamab in the DeLLphi-304 trial was comparable with prior reports of the agent. The most common adverse effects (AEs) among those who received tarlatamab included cytokine release syndrome (CRS; 56.7%), decreased appetite (36.4%), pyrexia (31.9%), dysgeusia (31.3%), constipation (30.4%), and anemia (30.0%). Additionally, CRS (19.7%) and pyrexia (4.7%) were the most frequent serious AEs.

“Patients with [SCLC] have historically [had] a hard road when they progress after initial treatment, surviving only a few months,” Debra Montague, president of Lung Cancer Europe, stated in the press release.¹ “Approval of a novel treatment option for [patients] in Europe living with this challenging cancer represents meaningful progress and underscores the urgent need for innovation in lung cancer care.”

Developers engineered tarlatamab to bind to both DLL3 on tumor cells as well as CD3 on T cells. This design facilitates T cells to target SCLC cells that express DLL3.

In the international phase 3 DeLLphi-304 study, 509 patients were randomly assigned 1:1 to receive tarlatamab (n = 254) or standard-of-care chemotherapy (n = 255). In the experimental arm, patients received tarlatamab at 1 mg on day 1 of cycle 1 followed by 10 mg on days 8 and 15 of cycle 1 and then 10 mg every 2 weeks afterwards in each 28-day cycle. Patients in the comparator arm received topotecan or lurbinectedin (Zepzelca).

The trial’s primary end point was OS. Key secondary end points included investigator-evaluated PFS and patient-reported outcomes.

Patients 18 years and older with SCLC who had progressed during or after frontline platinum-based therapy and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Those with brain metastases were permitted to enroll if they were asymptomatic and clinically stable.

The FDA previously granted traditional approval to tarlatamab for those with previously treated ES-SCLC in November 2025 based on data from the DeLLphi-304 trial.³

“[SCLC] is one of the most aggressive solid tumors, with high rates of relapse following first-line treatment and limited treatment options. The European Commission's approval of [tarlatamab], the first and only T-cell engager therapy approved to treat [SCLC], marks an important step forward for patients in Europe and reflects our commitment to advancing innovative medicines that can meaningfully improve outcomes for people living with this devastating disease,” Jean-Charles Soria, senior vice president of Oncology at Amgen, concluded.¹

References

1. European Commission approves Amgen’s Imdylltra® for the treatment of extensive-stage small cell lung cancer. News release. Amgen. June 1, 2026. Accessed June 5, 2026. https://tinyurl.com/mtndpuma
2. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cel lung cancer after platinum-based chemotherapy. N Engl J Med. 2025;393(4):349-361. doi:10.1056/NEJMoa2502099
3. FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. November 19, 2025. Accessed June 5, 2026.. https://tinyurl.com/yc7b96fw