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When combined with an anti–PD-L1 therapy, tarlatamab significantly improves overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC).
Research findings presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC) in Barcelona, Spain, demonstrated that a combination of tarlatamab (Imdelltra; Amgen) and an anti–PD-L1 therapy as a first-line maintenance treatment has an acceptable safety profile and resulted in unprecedented overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). The data are from the phase 1b DeLLphi-303 clinical trial (NCT05361395)2 and were simultaneously published in The Lancet Oncology.3
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Trial Name: First-Line Tarlatamab in Combination With Carboplatin, Etoposide, and PD-L1 Inhibitor in Subjects With Extensive Stage Small Cell Lung Cancer (ES-SCLC)
ClinicalTrials.gov ID: NCT05361395
Sponsor: Amgen
Completion Date (Estimated): August 28, 2028
ES-SCLC is an aggressive cancer with a poor long-term prognosis. Although most patients respond to first-line platinum-based chemotherapy that is administered alongside PD-L1 inhibitor therapy followed by a PD-L1 inhibitor in the first-line maintenance setting, relapse occurs quickly, with clinical trials reporting median progression-free survival (PFS) of about 5 months and median OS of 12 to 13 months from the time of randomization. Tarlatamab is a delta-like ligand 3-directed bispecific T-cell engager immunotherapy that has previously been shown to improve survival in patients with previously treated SCLC.3
In the multicenter, nonrandomized phase 1b clinical trial, DeLLphi-303, a total of 88 patients with ES-SCLC were enrolled from August 31, 2022, to January 30, 2024, and completed 4 to 6 cycles of platinum-etoposide chemotherapy and anti–PD-L1 without disease progression. Within 8 weeks following the initiation of their last chemoimmunotherapy cycle, patients began maintenance treatment with a tarlatamab regimen. For maintenance, patients received a 10-mg intravenous (IV) infusion of tarlatamab once every 2 weeks, after an initial 1-mg dose, with 1680 mg of IV atezolizumab (Tencentriq; Genentech) once every 4 weeks or 1500 mg of IV durvalumab (Imfinizi; AstraZeneca) once every 4 weeks as maintenance until disease progression.1-3
The trial’s primary objective was to evaluate safety and to determine the recommended phase 2 dose or maximum tolerated dose of tarlatamab in combination with a PD-L1 inhibitor through the assessment of dose-limiting toxicities, treatment-emergent adverse events (AEs), treatment-related AEs (TRAEs), and changes in vital signs, electrocardiograms, and clinical laboratory tests. At the time of the analysis, OS data were immature.2,3
The data show that after a median follow-up of 18.4 months, the median OS was about 25.3 months (95% CI, 20.3–not reached) and the median PFS was 5.6 months (95% CI, 3.5–9.0). The most common grades 3 and 4 AEs were hyponatremia (n = 9; 10%), anemia (n = 7; 8%), and neutropenia (n = 6; 7%). Serious AEs occurred in approximately 57% (n = 50) of patients, with the most common being cytokine release syndrome (n = 21; 24%), pyrexia (n = 6; 7%), immune effector cell-associated neurotoxicity syndrome (n = 4; 5%), and pneumonia (n = 4; 5%). Importantly, there were no observed deaths from TRAEs.1,3
“The combination of tarlatamab with anti–PD-L1 therapy as first-line maintenance demonstrates a manageable safety profile and unprecedented OS in this patient population,” lead DeLLphi-303 investigator KG Paulson, MD, Providence-Swedish Cancer Institute, Seattle, WA, said in a news release. “These results support further evaluation of this combination in the active phase 3 DeLLphi-305 trial (NCT06211036) as a promising therapeutic strategy in first-line ES-SCLC.”1
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