FDA Grants Approval to Tarlatamab in Small Cell Lung Cancer

• The FDA has given accelerated approved to tarlatamab-dlle (Imdelltra), a bispecific T-cell engager (BiTE) for the treatment of small cell lung cancer (SCLC) that has progressed on or after platinum-based chemotherapy.
• The approval is based on findings from the phase 2 DeLLphi-301 study (NCT05060016).
• This marks the first BiTE therapy to be approved for the treatment of a major solid tumor.

The FDA granted accelerated approval to tarlatamab for the treatment of patients with SCLC that has progressed on or after platinum-based chemotherapy, making it the first BiTE approved for a major solid tumor and the first therapeutic option for the treatment of extensive-stage SCLC.¹

The approval is supported by data from the phase 2 DeLLphi-301 trial that were published in the New England Journal of Medicine and presented at the 2023 European Society of Medical Oncology Congress. The objective response rate for patients treated with 10 mg of tarlatamab was 40% (97.5% CI, 29%-52%) vs 32% (97.5% CI, 21%-44%) with the 100-mg dose. Fifty-eight percent of patients in the 10-mg group responded to tarlatamab for at least 6 months compared with 61% in the 100 mg group.²

Among patients treated with either dose level, the median progression-free survival was 4.9 months (95% CI, 2.9-6.7) and 3.9 months (95% CI, 2.6-4.4), respectively, and the median overall survival (OS) was 14.3 months (95% CI, 10.8-not estimable [NE]) and NE (95% CI, 12.4-NE). While OS data were not mature, at the last follow-up, 57% of patients in the 10 mg group and 51% of those in the 100 mg group were still alive.

“Tarlatamab has shown manageable safety profile and activity,” Luis Paz-Ares, MD, PhD, chair of the medical oncology department at the Hospital Doce de Octubre, associate professor at the Universidad Complutense, and head of the lung cancer unit at the CNIO in Madrid, Spain, said during the presentation of the data. “We have chosen 10 mg to go to further development.”

The most common treatment-emergent adverse event (TEAE) was cytokine release syndrome (CRS), which occurred in 49% of patients in the 10-mg group and 61% in the 100-mg group. CRS primarily occurred during the first cycle and was mostly grade 1 or 2. Grade 3 CRS was seen in 5.7% of patients treated with the 100 mg dose.

TEAEs that led to either dose interruption or reduction were reported in 14% of patients treated with the 10 mg dose and 29% in those treated with the 100 mg dose.

In December 2023, the FDA granted priority review to the biologics license application of tarlatamab. In October 2023, tarlatamab was granted breakthrough therapy designation.³

“Tarlatamab represents a new immunotherapeutic approach for small cell lung cancer, a tumor type that is characterized by an immunosuppressive microenvironment,” the researchers wrote in the simultaneous publication of the findings in the New England Journal of Medicine.⁴

REFERENCES:

1. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. US FDA. May 16, 2024. Accessed May 16, 2024. https://tinyurl.com/bddwjpk2

2. Paz-Ares L, Ahn M, Felip E, et al. Tarlatamab for patients (pts) with previously treated small cell lung cancer (SCLC): Primary analysis of the phase II DeLLphi-301 study. Presented at: European Society for Medical Oncology Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA92.

3. FDA grants priority review to Amgen’s tarlatamab application for advanced small cell lung cancer. News release. Amgen. December 13, 2023. Accessed April 19, 2024. https://tinyurl.com/4zrvyfrk

4. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389(22):2063-2075. doi:10.1056/NEJMoa2307980