Tarlatamab Receives Standard FDA Approval in Extensive-Stage SCLC

The FDA has converted its 2024 accelerated approval of tarlatamab-dlle (Imdelltra) for the treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) with disease progression during or after platinum-based chemotherapy to a standard one.

The efficacy of tarlatamab in this patient population was evaluated in the multicenter, randomized, open-label phase 3 DeLLphi-304 (NCT05740566). Patients (n = 509) were randomized 1:1 to receive treatment with either tarlatamab or investigator’s choice of standard-of-care (SOC) chemotherapy (either topotecan, lurbinectedin, or amrubicin).

Overall survival (OS) was the primary efficacy measure, with progression-free survival (PFS) and certain patient-reported outcomes (PROs) being secondary measures. Tarlatamab was shown to reduce the risk of death by 40%, with patients in this patient population who received tarlatamab having a median OS of 13.6 months (95% CI, 11.1-not evaluable [NE]) vs 8.3 months (95% CI, 7.0-10.2) in the SOC arm (hazard ratio [HR], 0.60; 95% CI, 0.47-0.77; P < .001).

Further, tarlatamab reduced the risk of disease progression or death by 38%, with a median PFS of 4.2 months (95% CI, 3.0-4.4) in the tarlatamab arm compared with 3.2 months (95% CI, 2.9-4.2) in the SOC arm (HR, 0.72; 95% CI, 0.59-0.88; P < .001).

Patient-Reported Outcomes in Patients Receiving Tarlatamab

Notably, tarlatamab made significant improvements to dyspnea at week 18 to a statistically significant degree. Data from the primary analysis of DeLLphi-304 were presented at the 2025 American Society of Clinical Oncology Annual Meeting, reflecting that the mean improvement in dyspnea score from baseline to week 18 was 1.94 in the tarlatamab arm vs –7.20 in the chemotherapy arm (difference, –9.14; 95% CI, –12.64 to –5.64; P < .001).^2,3

Additionally, 16.1% of patients in the tarlatamab has improved cough scores at week 18 vs 9.0% of patients in the control group (odds ratio [OR], 2.04; 95% CI, 1.17-3.55; P = .012). Likewise, 8.7% and 3.5% of patients in each group, respectively, reported improvements in chest pain at week 18 (OR, 1.84; 95% CI, 0.89-3.81; P = .100); differences in chest pain improvement did not reach statistical significance.

In patients who were monitored for cytokine release syndrome (CRS) for at least 6 to 8 hours in the first 2 cycles of treatment with tarlatamab (n = 43), 37% of patients had CRS, at grade 1 in 28% and at grade 2 in 9% of patients had grade 2 CRS. CRS cases were serious in 7%, but none resulted in treatment discontinuation. The median time to intervention was 17 hours.

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 99% of patients in the experimental arm compared with all patients in the chemotherapy arm. The rates of any-grade treatment-related AEs (TRAEs) were 93% and 91%, respectively.

Grade 3 TRAEs occurred in 27% of patients in the tarlatamab group vs 62% of patients in the chemotherapy group, and respective rates of serious TRAEs were 28% and 31%. Dose interruption and/or reduction was caused by TRAEs in 19% of patients treated with tarlatamab and 55% given chemotherapy. Treatment discontinuation was caused by TRAEs in 3% and 6% of patients, respectively. One patient (0.4%) experienced a grade 5 TRAE in the tarlatamab arm compared with 4 patients (2%) in the chemotherapy arm.

At baseline, the median age was 64 years (range, 20-86) in the tarlatamab arm vs 66 years (range, 26-84) in the chemotherapy arm.

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://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
2. 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
3. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med. Published online June 2, 2025. doi:10.1056/NEJMoa2502099