Regulatory Decision Summary for Libtayo

The purpose of this supplemental new drug submission (SNDS) was to seek market authorization for Libtayo (cemiplimab), in combination with platinum-based chemotherapy, for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with no Epithelial Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) or ROS proto-oncogene 1 (ROS1) genomic tumour aberrations. After evaluation of the submitted data package, Health Canada authorized the use of Libtayo, in combination with platinum-based chemotherapy, for the first-line treatment of adult patients with NSCLC whose tumours have no EGFR, ALK or ROS1 aberrations; with locally advanced NSCLC where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC.

Market authorization for the use of Libtayo (cemiplimab) in combination with platinum-based chemotherapy, was based on the results of a controlled, phase 3, multicenter, randomized, 2-part trial designed to assess Libtayo combination therapy in the first-line treatment of patients with locally advanced or metastatic, squamous or non-squamous non-small cell lung cancer (NSCLC). The focus of this submission was part 2 of the study. The study was double-blinded and designed to compare Libtayo in combination with platinum-based chemotherapy (Libtayo plus chemotherapy) versus placebo in combination with platinum-based chemotherapy (placebo plus chemotherapy) in the first-line treatment of adult patients with squamous or non-squamous NSCLC with locally advanced disease (patients with stage IIIB or IIIC disease who were not candidates for curative surgery, definitive chemoradiotherapy) or metastatic disease (stage IV disease).

The primary efficacy analysis compared overall survival (OS) in the intent to treat population (ITT). A total of 466 patients were randomized 2:1 to receive Libtayo plus chemotherapy (n = 312) or placebo plus chemotherapy (n = 154). At the time of the second pre-specified interim analysis, the study met its primary objective demonstrating both a statistically significant and clinically meaningful improvement in the primary endpoint of OS for Libtayo plus chemotherapy over placebo plus chemotherapy in the ITT population. The median OS was estimated as 21.9 months for the Libtayo arm and 13.0 months for the chemotherapy arm, with a hazard ratio (HR) of 0.71 representing a 29% reduction in the risk of death with Libtayo plus chemotherapy. The OS result was supported by the key secondary endpoints of progression-free survival, objective response rate and duration of response.

While the OS in the ITT population was significant, there were inconsistencies in the treatment effect observed across key patient subgroups. The inconsistencies with respect to the subgroup results by sex, smoking status and histology could not be fully understood. These inconsistencies with the use of Libtayo, in combination with platinum-based chemotherapy, in the first-line treatment of advanced or metastatic NSCLC are captured in the Product Monograph. The Sponsor has committed, as a post-notice of compliance commitment, to submit the results of the final prespecified OS analysis for Part 2 of study 16113 as a supplemental new drug submission (SNDS) to Health Canada.

The most common adverse reactions reported in at least 20% of the patients who received Libtayo plus platinum-based chemotherapy included, anaemia, alopecia and nausea. The most common immune-mediated adverse reactions that occurred in the Libtayo plus chemotherapy arm were, hypothyroidism, pneumonitis, hyperthyroidism and ALT increased. The safety findings were consistent with the known safety profile for Libtayo. The risks associated with Libtayo, and risk mitigation strategies are adequately captured in the Product Monograph.

The recommended dose of Libtayo is 350 mg every three (3) weeks administered as an intravenous infusion over 30 minutes until symptomatic disease progression or unacceptable toxicity.

Overall, based on the evidence, the anticipated benefit outweighs the potential risks for the use of Libtayo, in combination with platinum-based chemotherapy, in patients with locally advanced or metastatic NSCLC whose tumors have no EGFR, ALK, or ROS1 aberrations. A Notice of Compliance (NOC) was issued.

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

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