The U.S. Food and Drug Administration (FDA) has granted approval for Imdelltra (tarlatamab) as a treatment option for adult patients grappling with extensive-stage small cell lung cancer (ES-SCLC) who have seen disease progression following platinum-based chemotherapy.
This accelerated approval comes on the heels of promising response rates and duration of response observed in clinical trials, although further confirmation of clinical benefit may be required for continued approval in this indication.
Imdelltra stands out as the pioneering DLL3-targeting Bispecific T-cell Engager therapy, designed to activate the patient's own T cells to combat DLL3-expressing tumor cells.
The FDA's accelerated approval of Imdelltra stems from findings in the Phase 2 DeLLphi-301 clinical trial, which assessed the therapy in SCLC patients who had undergone two or more prior lines of treatment, receiving the 10 mg every two weeks dosing (Q2W) regimen.
Results unveiled a robust objective response rate (ORR) of 40% and a median duration of response (DoR) reaching 9.7 months. Median overall survival (mOS) hit 14.3 months, with comprehensive survival data still pending maturation.
Imdelltra's label carries a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity, encompassing immune effector cell-associated neurotoxicity syndrome (ICANS), along with cautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity. Among reported adverse reactions, CRS, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea topped the list. Permanent discontinuations due to treatment-emergent adverse events (TEAEs) were rare at 7%. CRS incidents were largely confined to the first and second dose, predominantly grade 1 or 2, and typically managed with supportive care. Further details regarding Important Safety Information are provided below.
Imdelltra represents a groundbreaking immunotherapy designed to target DLL3 on tumor cells and CD3 on T cells simultaneously. By activating T cells to attack DLL3-expressing SCLC cells, Imdelltra fosters the formation of a cytolytic synapse, ultimately leading to cancer cell lysis. DLL3, a protein found on the surface of SCLC cells in approximately 85-96% of patients with SCLC, is minimally expressed on healthy cells, making it a particularly promising target for therapeutic intervention.
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