FDA Grants Full Approval to Tarlatamab in Small Cell Lung Cancer

The FDA has granted full approval to tarlatamab-dlle (Imdelltra) for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.¹

The approval is based on findings from the phase 3 DeLLphi-304 trial (NCT05740566), in which the bispecific T-cell engager tarlatamab reduced the risk of death by 40% vs investigator's choice of standard chemotherapy (HR, 0.60; 95% CI, 0.47-0.77; P <.001). The median overall survival (OS) was 13.6 months vs 8.3 months, respectively. Tarlatamab also reduced the risk of disease progression or death by 28% vs chemotherapy (median progression-free survival [PFS], 4.2 vs 3.2 months, respectively; HR, 0.72; 95% CI, 0.59-0.88; P <.001).

Tarlatamab was previously granted an accelerated approval in this setting. Continued approval of the treatment was contingent upon a confirmatory trial that would convert the accelerated approval into a full approval.

"Due to its distinctive biology and aggressive nature, small cell lung cancer has long been particularly challenging to treat, with limited progress compared to many other cancers. After years of research efforts, DeLLphi-304 was the first global Phase 3 trial to demonstrate a significant survival benefit over chemotherapy in its setting, leading to NCCN Guidelines Category 1 status for tarlatamab and further demonstrating the validity of this treatment approach in small cell lung cancer," Charles M. Rudin, MD, PhD, deputy director, Memorial Sloan Kettering Cancer Center, and principal investigator, stated in a news release.² "Importantly, data from DeLLphi-304 reflected in today's approval also equip physicians with a greater understanding of managing treatment with bispecific T-cell engager therapy."

Safety data for tarlatamab in the DeLLphi-304 trial were similar to previously reported safety results with the treatment in other trials. Fewer patients receiving tarlatamab experienced grade 3 or higher adverse events vs those receiving chemotherapy at 54% vs 80%, respectively. Among patients receiving tarlatamab, the most common grade 3 or higher treatment-related adverse events (TRAEs) were neutropenia (4%) and lymphopenia (4%). With chemotherapy, the most common TRAEs were anemia (28%) and neutropenia (22%).

Regarding cytokine release syndrome (CRS) in patients receiving tarlatamab, incidents occurred primarily following the first 2 doses and were generally low grade. Grade 1 CRS occurred in 42% of patients, grade 2 occurred in 13%, and grade 3 occurred in 1%. There were no reported grade 4 or grade 5 CRS events.

Also of note, compared with patients randomized to chemotherapy, patients receiving tarlatamab experienced a statistically significant improvement in dyspnea at week 18.

Overall, the open-label, randomized DeLLphi-304 trial enrolled patients 18 years and older who had histologically or cytologically confirmed SCLC with disease progression after a first-line, platinum-based regimen with or without an immune checkpoint inhibitor. Patients had to have an ECOG performance status of 0 or 1.³

Patients were randomized in a 1:1 ratio to receive tarlatamab (n = 254) or investigator's choice of chemotherapy consisting of lurbinectedin (n = 47), topotecan (n = 185), or amrubicin (n = 23).

The primary end point of the trial was OS. Secondary end points included PFS, patient-reported outcomes, objective response rate, duration of response, disease control rate, and safety.

The FDA label for tarlatamab-dlle includes a boxed warning for life-threatening or fatal CRS and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome. It also lists warnings and precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity.

REFERENCES

1. FDA grants traditional approval to tarlatamab-dlle for extensive-stage small-cell lung cancer. FDA. November 19, 2025. Accessed November 19, 2025. https://tinyurl.com/ycy7hety

2. FDA grants full approval to Amgen’s Imdelltra in extensive stage small cell lung cancer. News release. Amgen. November 19, 2025. Accessed November 19, 2025. https://www.amgen.com/newsroom/press-releases/2025/11/fda-grants-full-approval-to-amgens-imdelltra-in-extensive-stage-small-cell-lung-cancer

3. 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