NewsFlash – Imdelltra Approved for Small Cell Lung Cancer

Amgen received Accelerated Approval from the U.S. Food and Drug Administration (FDA) on May 16, 2024, for Imdelltra^™ (tarlatamab-dlle). It is indicated to treat adults who have extensive-stage small cell lung cancer (ES-SCLC) that is advancing either during or after treatment with a platinum-containing chemotherapy (chemo) regimen. The first drug in its class, Imdelltra is bispecific for delta-like ligand 3 (DLL3) proteins on SCLC cells and for a cluster of differentiation 3 (CD3) receptors on T-cells. Its initial dose is 1mg and then it increases to 10mg once a week for the first two-week cycle. Subsequent 10mg doses are scheduled once every two weeks. It is administered by intravenous (IV) infusions, which must be given in healthcare facilities where the patient can be watched for side effects. Observation periods gradually decrease from 24 hours after the first two doses to two hours following the fourth cycle of treatment. After an estimated wholesale acquisition cost (WAC) of $31,500 for the first cycle, each infusion will cost $30,000. One year of treatment is estimated to cost $781,500 according to Amgen. Launch and distribution plans have not yet been announced. Full prescribing information is here.

At a Glance

• Brand (Generic) Name: Imdelltra (tarlatamab-dlle)
• Manufacturer: Amgen
• Date Approved: May 16, 2024
• Indication: to treat adults who have ES-SCLC with disease progression on or after platinum-based chemo
• Dosage Forms Available: single-dose vials that contain 1mg or 10mg of powder for reconstitution and dilution
• Launch Date: to be determined
• Estimated Annual Cost: WAC is $781,500 for the first year
• Less common but typically more aggressive than non-small cell lung cancer (NSCLC), SCLC accounts for about 15% of lung cancer cases or around 35,000 new patients in the U.S. each year. Many patients have advanced SCLC at diagnosis. DLL3 is present on up to 96% of SCLC cells, but not on normal cells.
• The five-year survival rate for patients who have ES-SCLC averages less than 3%.
• Imdelltra is known as a Bispecific T-cell engager (BiTE). It attaches to DLL3 on the cancer cells and triggers CD3 on T-cells, causing the cancer cells to disintegrate.
• In the open-label, phase II DeLLphi-301 clinical study, 40% of the patients using Imdelltra responded to treatment for an average of 9.7 months. The median overall survival (OS) was 14.3 months.
• More than one-half of patients treated with Imdelltra developed cytokine release syndrome (CRS), a potentially severe inflammatory response that can cause organ dysfunction. Most cases were not severe, most happened during the first cycle and all the patients recovered. Labeling for Imdelltra has a boxed warning about the possibility of CRS and another possibly fatal adverse effect, immune effector cell-associated neurotoxicity syndrome (ICANS).
• Other frequent side effects in the clinical trial included anemia, constipation, fatigue, fever, musculoskeletal pain, and nausea. Some blood and electrolyte abnormalities also were seen.
• In addition to chemo, currently labeled drug treatment for ES-SCLC is limited to immunotherapy with the programmed death ligand 1 (PD-L1) antibodies, Imfinzi^® (durvalumab), or Tecentriq^® (atezolizumab).
• Approved under Priority Review, Imdelltra also has both Breakthrough and Orphan Drug status. Additionally, it was considered using Assessment Aid, Project Orbis, and Real-Time Oncology Review (RTOR) — some of the FDA’s procedures that speed up approvals for drugs that may fill critical unmet needs.
• Additional positive data from clinical trials will be needed before the FDA grants full approval for Imdelltra.