According to the American Cancer Society, more than 234,000 people will be diagnosed with lung cancer and 160,000 die from the disease every year, making it the leading cause of cancer death. SCLC primarily is associated with smoking and accounts for about 10 to 15 percent of all lung cancers. The survival for most SCLC patients is less than a year and there have been few recent advances in its treatment.
In 2024, the Food and Drug Administration granted accelerated approval to Imdelltra (tarlatamab-dlle) for the treatment of extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
In 2025, the FDA has converted tarlatamab-dlle (Imdelltra) to a traditional approval for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has worsened after platinum-based chemotherapy. In the phase 3 DeLLphi-304 trial, 509 patients were randomly assigned to receive either tarlatamab or standard chemotherapy (topotecan, lurbinectedin, or amrubicin); people who received tarlatamab lived a median of 13.6 months compared with 8.3 months on standard treatment, and also had a modest improvement in the time before their cancer worsened, along with better shortness of breath at 18 weeks.
Tarlatamab carries important safety risks, including a boxed warning for life-threatening cytokine release syndrome and neurologic side effects (such as ICANS), and other warnings for low blood counts, infections, liver problems, allergic reactions, and potential harm to an unborn baby, so patients should discuss benefits and risks carefully with their oncology team and review the full prescribing information.
About Imdelltra (tarlatamab)
Imdelltra is a bispecific T-cell engager (BiTE) that targets a Delta-like ligand 3 (DLL3) that activates a patient’s own T cells to attack DLL3-expressing tumor cells. Bispecific’s represent an innovative immunotherapy approach that help the body’s immune system target cancer cells. Bispecific antibodies or BiTE which is short for “bispecific T cell engager” are antibodies with two arms. One arm of the drug attaches to a specific protein on the cancer cell. The other arm of the BiTE activates immune cells in the patient to kill the cancer cells.
The FDA approval of Imdelltra was based on a trial in 99 patients with relapsed/refractory ES-SCLC who experienced disease progression following platinum-based chemotherapy. Imdelltra produced an overall response rate of 40% with a median duration of response of 9.7 months with some responses exceeding 20 months. Of the 69 patients with available data regarding platinum sensitivity status, the ORR was 52% (95% CI 32, 71) in 27 patients with platinum-resistant SCLC (defined as progression < 90 days after last dose of platinum therapy) and 31% (95% CI 18, 47) in 42 patients with platinum-sensitive SCLC (defined as progression ≥ 90 days after last dose of platinum therapy).
Patients with symptomatic brain metastases, interstitial lung disease or non-infectious pneumonitis, and active immunodeficiency were excluded. Patients received tarlatamab until disease progression or unacceptable toxicity.
References
- https://www.amgen.com/newsroom/press-releases/2024/05/fda-approves-imdelltra-tarlatamabdlle-the-first-and-only-tcell-engager-therapy-for-the-treatment-of-extensivestage-small-cell-lung-cancer
- Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Clin Cancer Res. 2021;27:1526-1537.
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
