Tarlatamab Demonstrates Positive Benefit-Risk Profile in SCLC
Tarlatamab showed a positive benefit-risk profile in small cell lung cancer, per the phase 2 DeLLphi-301 study.
Small cell lung cancer : © Ekaterina- stock.adobe.com
Treatment with tarlatamab-dlle (Imdelltra) had a positive benefit-risk profile when used in previously treated patients with small cell lung cancer (SCLC), according to patient-reported outcomes (PROs) from the phase 2 DeLLphi-301 study (NCT05060016).1
In a cohort of 100 PRO-evaluable patients receiving the target dose of 10 mg tarlatamab, the agent demonstrated manageable and sustained tolerability. Clinically meaningful reductions in dyspnea symptom burden (≥ 10-point improvement) were observed, particularly in later treatment cycles. Chest pain and cough symptoms remained stable. Further, the median time to deterioration (TTD) surpassed 6 months for both cough and dyspnea, while TTD for chest pain was not estimable.
Most patients reported minimal or no bother from treatment-related adverse events (AEs) after baseline. Patient-reported AEs were predominantly mild to moderate in severity and occurred infrequently or occasionally, suggesting a favorable tolerability profile for tarlatamab in this patient population.
In the phase 2 trial, patients were given tarlatamab intravenously every 2 weeks at a dose of 10 mg, which is the regulatory approved dose, or 100 mg until progression or loss of benefit.
PROs were assessed using several validated instruments, including the European organization for research and treatment of cancer 30-item quality of life questionnaire (EORTC-QLQ-C30), the 13-item lung cancer-specific module (QLQ-LC13), the patient-reported outcomes version of the common terminology criteria for AEs, and the GP5 question from the functional assessment of cancer therapy - general form. PRO data were collected at specific timepoints, including on days 1, 8, and 22 of cycle 1, days 1 and 15 of cycle 2, and every 6 weeks starting from cycle 3 onward.
Descriptive summaries of PROs were generated, including the extent and reasons for missing data. Statistical analysis was performed using a mixed model for repeated measures. Additionally, the median TTD for symptom and functional scales was evaluated.
Completion rates for the EORTC-QLQ-C30 and QLQ-LC13 remained consistently high (>80%) throughout the study period. Analysis of least square mean changes from baseline revealed a trend toward improvement in global health status and stabilization in physical functioning.
Previously, extended follow-up data from the phase 2 DeLLphi-301 study showed that tarlatamab led to sustained anticancer activity and manageable safety in patients with extended-stage SCLC previously treated with platinum-based chemotherapy.2
These data, which were presented at the 2024 World Conference on Lung Cancer,2,3 demonstrated that at a median follow-up of 13.6 months (range, 0.1-20.9) for efficacy evaluation, the overall response rate (ORR) was 40.4% among patients treated at the 10 mg dose. The median duration of response was not estimable among these patients.
Responses were ongoing in 47.5% (n = 19) of responders, the median progression-free survival was 4.3 months, and the median overall survival (OS) was 15.2 months in this group of patients. The 6- and 12-month estimated OS rates were 73.4% and 56.7%, respectively.
No new safety signals were identified, and the most common AE was cytokine release syndrome (CRS; 56.8%). Most AEs were grade 1 or 2, and there were no grade 4 or 5 AEs. Only 2.7% of patients discontinued treatment due to treatment-related AEs.
In May 2024, the FDA granted approval to the bispecific T-cell engager (BiTE) tarlatamab in this patient population based on the DeLLphi-301 study, making it the first BiTE therapy to be approved for the treatment of a major solid tumor.3
REFERENCES:
Hummel HD, Ahn MJ, Blackhall F, et al. Patient-reported outcomes for patients with previously treated small cell lung cancer receiving tarlatamab: results from the DeLLphi-301 phase 2 trial. Adv Ther. Published online March 3, 2025. doi:10.1007/s12325-025-03136-4
Sands J, Cho BC, Ahn MJ, et al. Tarlatamab sustained clinical benefit and safety in previously treated SCLC: DeLLphi-301phase 2 extended follow-up. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract OA10.03.
Amgen presents new data for first-in-class IMDELLTRA™ (tarlatamab-dlle) in small cell lung cancer at WCLC 2024. News release. Amgen. September 9, 2024. Accessed March 13, 2025. https://tinyurl.com/mpn27pa7
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