The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended granting a marketing authorization in the European Union for the use of tarlatamab (Imdylltra) monotherapy for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) who experience disease relapse during or after initial treatment with platinum-based chemotherapy.1
The positive CHMP recommendation was based on data from the phase 3 DeLLphi-304 study (NCT05740566), in which patients who received tarlatamab (n = 254) achieved a median overall survival (OS) of 13.6 months (95% CI, 11.1-not evaluable) vs 8.3 months (95% CI, 7.0-10.2) in those who received standard-of-care (SOC) therapy with topotecan, lurbinectedin (Zepzelca), or amrubicin (n = 255), translating to a 40% reduction in the risk of death (HR, 0.60; 95% CI, 0.47-0.77; P < .001).1,2 Additionally, the median progression-free survival (PFS) was 4.2 months (95% CI, 3.0-4.4) in the tarlatamab arm vs 3.2 months (95% CI, 2.9-4.2) in the SOC arm, translating to a 28% reduction in the risk of disease progression or death (HR, 0.72; 95% CI, 0.59-0.88; P < .001).
Highlighting the CHMP Recommendation for Tarlatamab in Relapsed ES-SCLC
- The EMA’s CHMP has recommended granting marketing authorization for tarlatamab to treat adult patients with ES-SCLC who have relapsed after platinum-based chemotherapy.
- Results from the DeLLphi-304 study showed that tarlatamab increased median OS to 13.6 months (95% CI, 11.1-not evaluable) compared with 8.3 months (95% CI, 7.0-10.2) with SOC treatments, which represents a 40% reduction in the risk of death (HR, 0.60; 95% CI, 0.47-0.77; P < .001).
- Tarlatamab also demonstrated clinical superiority over SOC therapy by providing a higher ORR of 35% (95% CI, 29%-41%) and significant improvements in patient-reported outcomes, such as cough and dyspnea.
What was the design of the DeLLphi-304 trial?
The randomized, open-label study enrolled 509 patients with ES-SCLC whose disease had relapsed after being treated with platinum-based chemotherapy with or without a PD-(L)1 inhibitor.
OS served as the primary end point. PFS and patient-reported outcomes (PROs) were key secondary end points. Other secondary end points included overall response rate (ORR), disease control rate, duration of response (DOR), and safety.2
What additional efficacy findings were seen in the DeLLphi-304 trial?
In the tarlatamab arm, the ORR was 35% (95% CI, 29%-41%) vs 20% (95% CI, 16%-26%) in the chemotherapy arm. Treatment with tarlatamab induced best responses of complete response (1%), partial response (PR; 34%), stable disease (SD; 33%), and progressive disease (PD; 22%). Treatment with SOC generated best responses of PR (20%), SD (44%), and PD (20%).
Patients who received tarlatamab had a median DOR of 6.9 months, including 6- and 12-month DOR rates of 56% and 41%, respectively. These respective values in the SOC arm were 5.5 months, 29%, and 13%. The median times to response were 1.5 months vs 1.4 months in these respective arms. At the data cutoff, 47% of patients in the tarlatamab arm remained in ongoing response vs 15% of those in the SOC arm.
What PROs have been seen with tarlatamab in ES-SCLC?
In DeLLphi-304, notable PRO outcomes included a mean improvement in dyspnea score from baseline to week 18 of 1.94 in the tarlatamab arm compared with –7.20 in the SOC arm (difference, –9.14; 95% CI, –12.64 to –5.64; P < .001). Furthermore, cough score improvements at week 18% were noted in 16.1% of patients who received tarlatamab vs 9.0% of those who received SOC (odds ratio [OR], 2.04; 95% CI, 1.17-3.55; P = .012). Additionally, the rates of chest pain improvements at week 18 were 8.7% and 3.5% in these respective arms (OR, 1.84; 95% CI, 0.89-3.81; P = .100).
What is the safety profile of tarlatamab?
Common adverse effects experienced by patients who received tarlatamab in DeLLphi-304 included cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, decreased appetite, fever, dysgeusia, constipation, anemia, fatigue, nausea, asthenia, neutropenia, hyponatremia, headache, and lymphopenia.1,2
What is the regulatory history of tarlatamab in SCLC?
On January 12, 2024, the EMA designated tarlatamab as an orphan medicinal product for the treatment of patients with SCLC.1
In the US, tarlatamab-dlle (Imdelltra) received FDA approval on November 19, 2025, for the treatment of patients with ES-SCLC who experience disease progression on or after treatment with platinum-based chemotherapy.3
References
- New treatment for relapsed extensive-stage small cell lung cancer. EMA. March 27, 2026. Accessed March 27, 2026. https://www.ema.europa.eu/en/news/new-treatment-relapsed-extensive-stage-small-cell-lung-cancer
- Rudin C, Mountzios G, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304. J Clin Oncol. 2025;43(suppl 17):LBA8008. doi:10.1200/JCO.2025.43.17_suppl.LBA8008
- FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. November 19, 2025. Accessed March 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
