Promising Trial Results for New Drug Under Investigation for Small Cell Lung Cancer

The FDA has granted priority review to Amgen's application for tarlatamab, an investigational therapy for advanced small cell lung cancer (SCLC). The FDA's priority review designation indicates the need for new treatment options in this patient population.

SCLC is a particularly aggressive form of lung cancer with a 5-year relative survival rate of 7%. Current treatments have limited success in advanced stages of the disease.

Tarlatamab is a type of immunotherapy drug called a bispecific T-cell engager (BiTE). The drug molecule has two “arms” that attach to SCLC cells and T cells at the same time, bringing them within close proximity. This helps the patient’s own immune system recognize and destroy the cancer cells. One of tarlatamab's arms attaches to a specific protein called DLL3, which is often present at high levels on the surface of SCLC cells.

The priority review application follows the results of the DeLLphi-301 phase 2 clinical trial, which demonstrated encouraging survival outcomes in patients with previously treated SCLC. In this trial, tarlatamab treatment successfully reduced tumor size in approximately one-third of participants. The results were published on November 30th in the New England Journal of Medicine.

The phase 2 trial was conducted to assess the effectiveness and safety of tarlatamab in patients with previously treated small-cell lung cancer (SCLC). The primary goal of the study was to assess participants’ complete or partial response, as evaluated by independent review using established evaluation criteria for solid tumor response.

The trial included over 200 patients with advanced SCLC whose cancer had progressed after at least two previous treatments. The trial participants received intravenous administration of tarlatamab every 2 weeks at a dose of either 10 milligrams (mg) or 100 mg.

Tumors shrank in 40% of patients who received the 10-mg dose and in about 32% of those who received the 100-mg dose. In more than half of the patients whose tumors shrank, the cancer did not progress for at least 6 months. The lower dose of tarlatamab will be used in future clinical trials based on these results.

The side effects were generally manageable, with only about 3% of participants stopping treatment due to side effects. The most common side effect was cytokine release syndrome. Other side effects included decreased appetite, fever, and anemia. Serious cases of cytokine release syndrome and immune effector cell−associated neurotoxicity syndrome (ICANS) were observed.

Note that the trial did not directly compare tarlatamab to standard therapy for SCLC. Additionally, researchers are still investigating biomarkers that may help predict which patients are more likely to respond to tarlatamab.

The FDA’s target action date is June 12, 2024. If approved, tarlatamab would become the first BiTE therapy indicated for a major solid tumor.