The Food and Drug Administration (FDA) has granted accelerated approval to tarlatamab-dlle (Imdelltra, Amgen, Inc.) for the treatment of extensive stage small cell lung cancer (ES-SCLC) in patients with disease progression following platinum-based chemotherapy. Tarlatamab-dlle is an innovative bi-specific T-cell engager designed to direct the body’s immune response specifically towards cancer cells. This mechanism allows for targeted treatment of SCLC, potentially improving outcomes for patients who have exhausted other treatment options.
Image Source: Vinoth Khandelwal
Tarlatamab-dlle has been approved under the FDA’s accelerated approval program, based on data from clinical trials demonstrating efficacy in treating ES-SCLC. This accelerated approval is contingent upon further verification of clinical benefits in ongoing studies. Additionally, tarlatamab-dlle was reviewed through several expedited FDA programs, including priority review, breakthrough designation, and orphan drug designation.
The approval was based on results from the DeLLphi-301 study (NCT05060016), an open-label, multicenter, multi-cohort clinical trial evaluating the efficacy and safety of tarlatamab-dlle. The study included 99 patients with relapsed or refractory ES-SCLC who had experienced disease progression after platinum-based chemotherapy. Exclusion criteria included symptomatic brain metastases, interstitial lung disease, non-infectious pneumonitis, and active immunodeficiency. Patients received tarlatamab-dlle until disease progression or unacceptable toxicity.
The major efficacy outcomes measured were overall response rate (ORR) and duration of response (DOR), assessed by blinded independent central review. The ORR was 40% (95% CI: 31, 51), and the median DOR was 9.7 months (range 2.7 to 20.7+ months). Among 69 patients with known platinum sensitivity status, the ORR was 52% (95% CI: 32, 71) for those with platinum-resistant SCLC (progression within 90 days of last platinum dose) and 31% (95% CI: 18, 47) for those with platinum-sensitive SCLC (progression ≥ 90 days post-treatment).
This application was reviewed under Project Orbis, an initiative of the FDA Oncology Center of Excellence, allowing for concurrent submission and review among international regulatory partners. Collaborators included the Brazilian Health Regulatory Agency (ANVISA), Health Canada (HC), Israel’s Ministry of Health (IMoH), and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). Additionally, the Real-Time Oncology Review (RTOR) pilot program and the Assessment Aid facilitated a more efficient review process, leading to approval one month ahead of the FDA’s goal date.
The accelerated approval of tarlatamab-dlle marks a significant advancement in the treatment of ES-SCLC, offering new hope for patients with limited options. Continued studies will be essential to confirm its clinical benefits and ensure long-term safety and efficacy. Healthcare professionals are encouraged to report serious adverse events associated with this medication to the FDA’s MedWatch Reporting System.
Dr. Vinoth Khandelwal, Ph.D.
