Regulatory Decision Summary for Imdelltra

The purpose of this submission was to seek marketing authorization with conditions for Imdelltra (tarlatamab), a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager, for the treatment of adult patients with small cell lung cancer (SCLC) with disease progression on or after at least two prior lines of therapy.

After evaluation, Imdelltra was authorized with conditions for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after at least two prior lines of therapy including platinum-based chemotherapy.

This submission was filed under the Notice of Compliance with Conditions (NOC/c) Guidance.

The submission was classified as a Project Orbis Type B submission and Health Canada collaborated with the United States Food and Drug Administration (FDA), Brazilian Health Regulatory Agency (Anvisa), UK Medicines and Healthcare Products Regulatory Agency (MHRA), Singapore Health Sciences Authority (HSA), and Israel Ministry of Health (MoH) for the review.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Authorization was based on the results of a phase 2, open-label, single arm trial in 99 patients with extensive-stage small cell lung cancer (SCLC) who had disease progression following 2 prior lines of treatment including platinum-based chemotherapy. Patients received intravenous infusions of 1 mg tarlatamab on Day 1 of Cycle 1, followed by 10 mg on Days 8 and 15 of Cycle 1 and thereafter 10 mg every 2 weeks until disease progression or intolerable toxicity.

The primary efficacy outcome was the objective response rate (ORR) as determined by a Blinded Independent Review Committee (BIRC). The reported ORR was 40.4% and the median duration of response was not reached after 8.3 months of follow-up. An improvement in survival has not been established. The benefit of Imdelltra in terms of overall survival will be evaluated in an ongoing randomized Phase 3 clinical trial which is required as a commitment to the Notice of Compliance with conditions.

The safety of Imdelltra was evaluated in 187 patients with relapsed or refractory SCLC. The most commonly reported adverse events (≥20%) were cytokine release syndrome (CRS), fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia and nausea. Key safety concerns include CRS, neurologic toxicities (including Immune Effector Cell-Associated Neurotoxicity Syndrome [ICANS]), tumour lysis syndrome, infections, cytopenias, and hepatotoxicity. The safety findings and applicable risk mitigation and management measures are described in the Imdelltra Product Monograph (PM).

An updated Risk Management Plan (RMP) for Imdelltra was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Imdelltra has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Health Canada granted this submission advanced consideration in accordance with the Notice of Compliance with conditions (NOC/c) policy.

For more information on the conditions issued, please refer to the Notice of Compliance with conditions (NOC/c) Website.

Overall, the benefit-harm-uncertainty profile was favourable for Imdelltra, 1 mg/vial and 10 mg/vial, for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Imdelltra, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.