Qualifying Notice - Lumakras

Therapeutic Products Directorate
Holland Cross, Tower "B"
6th Floor, 1600 Scott Street
Address Locator #3106B
Ottawa, Ontario
K1A 0K9

Dossier ID: e230960

[employee name removed]
[employee's title removed]
[name of company removed]

Dear [employee name removed]:

This Notice of Compliance with Conditions-Qualifying Notice (NOC/c-QN), issued in accordance with the Health Canada Guidance Document: Notice of Compliance with Conditions (NOC/c), is to advise you that information submitted in support of the New Drug Submission for Lumakras (sotorasib), control number 248435, for the indication of the treatment of adult patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C-mutated locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy, qualifies to be considered for authorization in accordance with the NOC/c Guidance. In keeping with the provision outlined in the NOC/c Guidance, the following additional information is required to complete the assessment:

1. A letter, signed by the Chief Executive Officer, or designated signing authority of [name of company removed], indicating that you agree to have this submission considered under the NOC/c Guidance. Please be reminded that in agreeing to accept a Notice of Compliance (NOC) under the NOC/c Guidance, [name of company removed] consents to the posting of this NOC/c-QN on Health Canada's website once market authorization has been received.
2. A Letter of Undertaking signed by the Chief Executive Officer, or designated signing authority of [name of company removed] having a form and content satisfactory to Health Canada, as indicated in NOC/c Guidance, including commitments to provide the following:

Confirmatory studies

1. Submit the final report, as a Supplemental New Drug Submission-Confirmatory (SNDS-C), from the 126 NSCLC patients with a KRAS-G12C mutation enrolled in the Phase 2 portion of the [trial identifier removed] study to verify and describe the clinical benefit and further characterize the duration of response in patients who achieved a complete or partial response to sotorasib. All responding patients will be followed for at least 2 years from the onset of response or until disease progression, whichever comes first.
2. Submit the final report, as a SNDS-C, from the randomized dose-optimization sub-study [trial identifier removed]. The study should further characterize serious adverse events, including gastro-intestinal toxicity and compare the safety and efficacy of sotorasib 960mg daily (RP2D) versus a lower daily dose in patients with locally advanced or metastatic, KRAS G12C mutated, non-small cell lung cancer who have received at least one prior systemic therapy.
3. Submit the final report, as a SNDS-C, from the multicenter, randomized clinical trial and submit the final progression-free survival (PFS) results that verifies and describes the clinical benefit of sotorasib in patients with locally advanced or metastatic non-small cell lung cancer with a history of prior systemic therapy for advanced disease and whose tumors harbor Kirsten rat sarcoma (KRAS) G12C mutation [trial identifier removed].

Additional studies

4. Submit the final report of the clinical drug interaction study to assess the effect of concomitant sotorasib administration on the systemic exposure of BCRP transporter substrates.
5. Submit the final report, as a Supplemental New Drug Submission (SNDS), of the hepatic impairment clinical trial to determine a safe and appropriate dose of sotorasib in patients with moderate and severe hepatic impairment.

Post market safety monitoring studies

1. Provision of annual Periodic Benefit-Risk Evaluation Reports (PBRER-Cs) or Periodic Safety Update Reports (PSUR-Cs) in a manner deemed consistent with E2C ICH Guidelines, until such time as all conditions for market authorization under the NOC/c Guidance have been removed. The annual PBRER-Cs or PSUR-Cs should include cumulative data on relevant unlisted Adverse Reactions (ARs) from the date of marketing to the time of the report.
2. Notification and reporting on specific issues of concern, as outlined in Section 3.4.4, Post-Market Commitments: Notification and Reporting of Specific Issues of Concern, of the Health Canada NOC/c Guidance.
3. Report(s) of all serious adverse drug reactions (ADRs) that occurred in Canada and all serious unexpected ADRs that occurred outside of Canada should be forwarded within 15 days to the Marketed Health Products Directorate, in accordance with the current Food and Drug Regulations (C.01.017) and guidance documents.

Labels

1. A draft of the Product Monograph (PM) that is consistent with the requirements outlined in section 5.2.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). Please note that boxed text should appear on the cover page as well as at the beginning of each major section of the Product Monograph (Parts I, and III, as applicable), disclosing the nature of the authorization granted for Lumakras for the indication of the treatment of adult patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C-mutated locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy.
2. A final mock-up of the Package Insert (if applicable), in line with the requirements outlined in Health Canada's Guidance Document, Questions and Answers: Plain Language Labelling Regulations (Q&A: PLL), containing boxed text disclosing the nature of the authorization granted for Lumakras for the indication of the treatment of adult patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C-mutated locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy.

I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada's guidance documents on the Management of Drug Submissions and Applications and Notice of Compliance with Conditions. Sponsors are instructed to submit a complete response [refer to Guidance Document: Notice of Compliance with Conditions (NOC/c)] with the requested information within 30 calendar days of the date of this letter.

In order to facilitate and to ensure proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to the Office of Submissions and Intellectual Property, Therapeutic Products Directorate, Finance Building, 101 Tunney's Pasture Driveway, Address Locator 0201A1, Tunney's Pasture, Ottawa, Ontario, K1A 0K9.

Yours sincerely,

[employee name removed]
[employee title removed]
Therapeutic Products Directorate
JPS/oh