Tarlatamab Remains Safe and Effective in Extensive-Stage SCLC

Results from the DeLLphi 303 trial showed sustained efficacy and safety with tarlatamab plus anti-PD-1 treatment for patients with extensive-stage SCLC.

Tarlatamab-dlle (Imdelltra) plus an anti-PD-1 therapy retained long-term durability in the first-line for patients with extensive-stage small cell lung cancer, according to results from the phase 1 DeLLphi 303 trial (NCT05361395) presented at the 2025 World Conference on Lung Cancer.¹

The median overall survival (OS) was 25.3 months (95% CI, 20.3-not evaluable [NE]) in the tarlatamab plus atezolizumab (Tecentriq) arm and NE (95% CI, 19.9-NE) in the tarlatamab plus durvalumab (Imfinzi) arm. Overall, the OS for tarlatamab plus anti-PD-L1 therapy was 25.3 months (95% CI, 20.3-NE). At 12 months, the OS rate was 82%. The median follow-up was 18.4 months.

The median progression-free survival (PFS) was 5.6 months (95% CI, 2.0-14.9) in the tarlatamab plus atezolizumab group and 5.3 months (95% CI, 3.5-11.2) in the tarlatamab plus durvalumab group. The overall PFS with tarlatamab plus anti-PD-L1 therapy was 5.6 months (95% CI, 3.5-9.0). The PFS rate at 12 months was 34%.

The overall response rate was 24%, with 2 complete responses (CRs) and 19 partial responses (PRs), and a median duration of 16.6 months (95% CI, 7.1-NE). The overall disease control rate (DCR) was 60% with 2 CRs, 19 PRs, and 32 patients with stable disease, and the median duration of DCR was 14.6 months (95% CI, 7.2-18.4). A total of 24% of patients remained on treatment at data cutoff, with 36% of patients having sustained disease control at 52 weeks or more.

“The addition of tarlatamab to anti-PD-L1 as [first line] maintenance therapy for [extensive-stage small cell lung cancer] demonstrates a manageable safety profile, sustained disease control, and unprecedented OS,” Kelly G. Paulson, MD, from Swedish Health Services, noted during the presentation.¹

The trial enrolled 88 patients, and they were given first-line maintenance of tarlatamab at 10 mg intravenously every 2 weeks plus atezalizumab at 1680 mg intravenously every 4 weeks, or tarlatamab plus durvalumab at 1500 mg intravenously every 4 weeks. Patients were included in the trial if they had no disease progression after 4 to 6 cycles of first-line chemoradiotherapy, an ECOG performance status of 0 or 1, treated and asymptomatic brain metastases, and no active autoimmune disease or disease requiring immunosuppressive therapy.

The primary end point was dose-limiting toxicities, treatment-emergent, and treatment-related adverse effects. The secondary end points included PFS, OS, ORR, duration of response, and disease control.

In the tarlatamab/atezolizumab arm (n = 48), the median age was 64 years, 67% of patients were male, 71% were White, 63% had an ECOG performance status of 1, and 19% and 31%, respectively, had brain/liver metastases.

In the tarlatamab/durvalumab arm, the median age was 64, 58% of patients were male, 70% were White, 55% had an ECOG performance status of 1, and 33% and 43%, respectively, had brain/liver metastases.

The median duration of treatment for tarlatamab was 35 weeks, 28 weeks for atezolizumab, and 31 weeks for durvalumab. All grade treatment-emergent adverse effects (TEAEs) were noted in 100% of patients. Tarlatamab-related AEs were observed in 98% of patients, with grade 3/4 events occurring in 27%, 38% were serious, 23% led to dose interruption or reduction, and 6% led to discontinuation.

The most common TEAEs included cytokine release syndrome (CRS; 56%), dysgeusia (53%), fatigue (38%), headache (32%), decreased appetite (31%), nausea (31%), and pyrexia (28%). Immune effector cell-associated neurotoxicity syndrome occurred in 6% of patients, all at less than 3 months of treatment. CRS typically occurred after the first or second dose of tarlatamab in cycle 1, with all events being resolved.

Additionally, these results were simultaneously published in The Lancet Oncology.²

References

1. Paulson KG, Lau SCM, Ahn MJ, et al. Safety and survival update of tarlatamab with anti-PD-L1 as first-line maintenance after chemo-immunotherapy for extensive-stage small cell lung cancer: DeLLphi-303 ph1b trial. Presented at the 2025 World Conference on Lung Cancer; Barcelona, Spain; September 6-9, 2025. Abstract OA13.
2. Paulson KG, Lau SCM, Ahn MJ, et al. Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): a multicentre, non-randomised, phase 1b study. Lancet Oncol. September 8, 2025.