Regulatory Decision Summary for Lumakras

The purpose of this Supplement to a New Drug Submission (SNDS) Comparative Studies/Chemistry and Manufacturing (Comp-C&M) – Response to Notice of Deficiency (NOD) was to propose a new 240 mg strength tablet for Lumakras, filed by the sponsor. Lumakras is currently authorized in Canada as a 120 mg tablet.

Pivotal phase 3 safety and efficacy studies were not conducted with the proposed 240 mg tablet. Instead, the sponsor’s strategy was to bridge the safety and efficacy data from the currently marketed 120 mg tablet to the proposed 240 mg tablet.

At the time of initial review, the submission was not considered to meet the requirements of the Food and Drugs Act and Regulations due to concerns related to comparative bioavailability between the currently marketed 120 mg tablet and the proposed 240 mg tablet, as well as other quality issues. A Notice of Deficiency was issued on January 8, 2024. The sponsor submitted responses to the Notice of Deficiency (NOD), which were reviewed and found acceptable with respect to quality and comparative bioavailability.

The drug product is manufactured by dry granulation via roller compaction and coated with a cosmetic coating with a 32 percent weight-to-weight drug loading. The approved 120 mg and proposed 240 mg tablets are not proportional in composition, with lactose monohydrate content differing at 19 percent and 7 percent respectively, exceeding limits outlined in Appendix 6 of Health Canada’s guidance Post-Notice of Compliance Changes: Quality Document. Both strengths are manufactured at the same site, Patheon Inc., Canada. Bioequivalence Study 20210088 was submitted to support the addition of the 240 mg strength. The formulation and manufacturing process used for the biolot CHZGG were found to be representative of those proposed for commercial lots. No changes were proposed to the approved indication. As per the original New Drug Submission, the International Council for Harmonisation S9 guideline remained applicable. Proposed impurity limits for the drug substance and drug product were considered acceptable and unchanged for the new strength. All quality concerns were resolved satisfactorily.

Study 20210088 demonstrated comparable sotorasib bioavailability between the proposed 240 mg tablet and the currently marketed 120 mg tablet administered as a single 240 mg dose under fasting conditions. The study also showed a food effect on the 240 mg tablet similar to that previously observed with the 120 mg tablet. It was considered that the safety and efficacy profiles clinically characterized at the 240 mg dose from the 120 mg tablet formulation could be extrapolated to the proposed 240 mg tablet. The similar food effect between tablet strengths supported dosing instructions for the 240 mg tablet that were consistent with those previously accepted and currently recommended in the Product Monograph for Lumakras 120 mg tablets, that is, with or without food.

The information submitted in response to the NOD supported the approval of the 240 mg strength. A Notice of Compliance with Conditions was recommended, as the new strength is to be used within the approved indication for Lumakras authorized under the Notice of Compliance with Conditions Guidance. For more information on the conditions issued, please refer to the Notice of Compliance with Conditions (NOC/c) website.

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