Profile
General Information
Imdelltra (tarlatamab-dlle) is a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager.
Imdelltra is specifically indicated for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
Dosing/Administration
Imdelltra is supplied as an injection for intravenous use only.
Administer Imdelltra according to the step-up dosing schedule in the drug label to reduce the incidence and severity of cytokine release syndrome (CRS).
For Cycle 1, administer recommended concomitant medications per the drug label before and after Cycle 1 Imdelltra infusions to reduce the risk of CRS reactions
Imdelltra should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and 4 of 30 neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS).
Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the Imdelltra infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting
Recommend that patients remain within 1-hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with Imdelltra following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.
Prior to administration of Imdelltra evaluate complete blood count, liver enzymes and bilirubin before each dose, and as clinically indicated
Ensure patients are well hydrated prior to administration of Imdelltra.
Administer Imdelltra as an intravenous infusion over one hour . After step-up dosing schedule, administer Imdelltra biweekly (every 2 weeks) until disease progression or unacceptable toxicity.
Mechanism of Action
Imdelltra (tarlatamab-dlle) is a bispecific T-cell engager that binds to DLL3 expressed on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. Tarlatamab-dlle causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells. Tarlatamab-dlle had anti-tumor activity in mouse models of SCLC.
Side Effects
Adverse effects associated with the use of Imdelltra may include, but are not limited to, the following:
- cytokine release syndrome
- fatigue
- pyrexia
- dysgeusia
- decreased appetite
- musculoskeletal pain
- constipation
- anemia
- nausea
- Grade 3 or 4 laboratory abnormalities (≥2%): decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, decreased potassium, increased aspartate aminotransferase, decreased white blood cells, decreased platelets, and increased alanine aminotransferase.
The Imdelltra drug label comes with the following Black Box Warning:
- Cytokine release syndrome (CRS), including serious or life threatening reactions, can occur in patients receiving Imdelltra. Initiate treatment with the Imdelltra using step-up dosing schedule to reduce the incidence and severity of CRS. Withhold Imdelltra until CRS resolves or permanently discontinue based on severity.
- Neurologic toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including serious or life threatening reactions, can occur in patients receiving Imdelltra. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold Imdelltra until ICANS resolves or permanently discontinue based on severity.
Clinical Trial Results
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The FDA accelerated approval of Imdelltra is based on results from the Phase 2 DeLLphi-301 clinical trial that evaluated Imdelltra in patients with SCLC who had failed two or more prior lines of treatment, and who had received the 10 mg every two weeks dosing (Q2W) regimen. Results from the study found that Imdelltra at the 10 mg Q2W dose (N=99) demonstrated a robust objective response rate (ORR) of 40% and median DoR of 9.7 months. The median overall survival (mOS) was 14.3 months, with final and complete survival data yet to mature at the time of approval.