FDA Approves Tarlatamab-Dlle to Treat Adults With Extensive Stage Small Cell Lung Cancer

The FDA approved tarlatamab-dlle (Imdelltra; Amgen) for the treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. The approval is supported by positive efficacy findings from the phase 3 DeLLphi-304 (NCT05740566) clinical trial.^1,2

Tarlatamab is a bispecific delta-like ligand 3-directed T-cell engager immunotherapy that was evaluated in the DeLLphi-304 trial. In May 2024, tarlatamab received an accelerated approval for this indication.³

It is recommended that tarlatamab be initiated with a 1-mg dose on day 1 of cycle 1, then followed by 10-mg doses on days 8 and 15, and every 2 weeks thereafter until disease progression or unacceptable toxicity.¹

The Phase 3 DeLLphi-304 Clinical Trial Evaluating Tarlatamab

DeLLphi-304 is a multicenter, multinational, randomized, open-label clinical trial evaluating the second-line treatment of tarlatamab in patients with SCLC with disease progression following treatment with platinum-based chemotherapy with or without an anti–PD-L1 antibody. A total of 509 patients were randomly assigned to receive either tarlatamab (n = 254) or investigator’s choice of standard of care chemotherapy—either topotecan, lurbinectedin, or amrubicin—(n = 255) until disease progression or unacceptable toxicity.^1,2,4

The trial’s primary end point was overall survival (OS), which was assessed up to approximately 4 years. Key secondary end points were investigator-assessed progression-free survival (PFS) and patient-reported outcomes, among others. Results of the prespecified interim analysis (data-cutoff date: January 29, 2025) were published in The New England Journal of Medicine.^1,2,4

Results

The trial results demonstrated a significantly longer OS in patients treated with tarlatamab (median OS: 13.6 months [95% CI 11.1, not evaluable]) compared with the standard of care (median OS: 8.3 months [95% CI 7.0, 10.2]; HR 0.60 [95% CI: 0.47, 0.77]; P < .001). Median PFS was also superior in the tarlatamab group (4.2 months [95% CI 3.0, 4.4]) than in the standard of care group (3.2 months [95% CI 2.9, 4.2]; HR 0.72 [95% CI 0.59, 0.88]; P < .001). Further, the trial also demonstrated a statistically significant improvement in dyspnea at week 18 for patients who were randomly assigned to tarlatamab compared with standard of care.^1,4

During the trial, the incidence of adverse events (AEs) of grade 3 or higher was lower with tarlatamab (54%) than with chemotherapy (80%), as was the incidence of AEs that resulted in treatment discontinuation (5% vs 12%, respectively).⁴

What Should Pharmacists Know About Tarlatamab?

The prescribing information for tarlatamab includes a boxed warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. Additional warnings and precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity are also emphasized. Pharmacists should be aware of the FDA-recommended dosing for tarlatamab so they can accurately educate patients on the correct treatment regimen and guide them during the process.¹

REFERENCES

1. US Food & Drug Administration. FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. November 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer

2. Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer (DeLLphi-304). ClinicalTrials.gov identifier: NCT05740566. Updated October 3, 2025. Accessed November 19, 2025. https://www.clinicaltrials.gov/study/nct05740566

3. Ferruggia K. The FDA Grants Accelerated Approval to Tarlatamab-dlle in Small Cell Lung Cancer. Pharmacy Times. May 17, 2024. Accessed November 19, 2025. https://www.pharmacytimes.com/view/the-fda-grants-accelerated-approval-to-tarlatamab-dlle-in-small-cell-lung-cancer

4. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. N Engl J Med. 2025;393(4):349–361. doi:10.1056/NEJMoa2502099