This evaluation was facilitated through Project Orbis, an initiative of the United States (US) Food and Drug Administration (FDA) Oncology Center of Excellence (OCE). Under this project, the FDA, Health Canada (HC) and the TGA collaboratively reviewed the application. This innovative evaluation process provided a framework for process alignment and management of evaluation issues in real-time across jurisdictions.
Each regulator agency maintained its regulatory process to make independent decisions about the approval (market authorisation).
|Designation (Provisional) |
|7 January 2021 |
10 November 2020
|Submission dossier accepted and first round evaluation commenced||1 March 2021|
|First round evaluation completed||30 July 2021|
|Sponsor provides responses on questions raised in first round evaluation||31 August 2021|
|Second round evaluation completed||13 December 2021|
|Delegate's overall benefit-risk assessment and request for Advisory Committee advice||3 November 2021 and |
10 January 2022
|Sponsor's pre-Advisory Committee response||16 November 2021 and |
24 January 2022
|Advisory Committee meeting||2 and 3 December 2021 and |
3 and 4 February 2022
|Registration decision (Outcome)||28 March 2022|
|Completion of administrative activities and registration on ARTG||30 March 2022|
|Number of working days from submission dossier acceptance to registration decision*||244|
*Statutory timeframe for standard applications is 255 working days
The recommended dose of Lumakras is 960 mg (as 8 x 120 mg tablets) orally once daily until disease progression or unacceptable toxicity.
For further information refer to the Product Information.
Lumakras (sotorasib) was approved for the following therapeutic use:
Lumakras has provisional approval in Australia for the treatment of adult patients with KRASG12C mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy for advanced disease.
The decision to approve this indication has been made on the basis of the objective response rate (ORR) and the duration of response (DOR). Continued approval of this indication depends on the verification and description of benefit in confirmatory trials.
- Lumakras (sotorasib) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Lumakras must include the black triangle symbol and mandatory accompanying text for the products entire period of provisional registration.
- The Lumakras European Union (EU) risk management plan (RMP) (version 0.2, dated 25 June 2021, data lock point 1 September 2020), with Australian specific annex (version 2.0, dated 18 August 2021), included with Submission PM 2021 00026 1 4, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
Unless agreed separately between the supplier who is the recipient of the approval and the TGA, the first report must be submitted to TGA no later than 15 calendar months after the date of the approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report until the period covered by such reports is not less than three years from the date of the approval letter, or the entire period of provisional registration, whichever is longer.
The reports are to at least meet the requirements for periodic safety update reports (PSURs) as described in the European Medicines Agency's guideline on Good Pharmacovigilance Practices (GVP) Module VII periodic safety update report (revision 1), Part VII.B structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration. Each report must have been prepared within ninety calendar days of the data lock point for that report.
- Confirmatory trial data (as identified in the sponsor's plan to submit comprehensive clinical data on the safety and efficacy of the medicine before the end of the 6 years that would start on the day that registration would commence) must be provided.
Specifically, the sponsor must conduct studies as described in the clinical study plan in version x 2.0 (dated 18 August 2021) of the Australia specific annex.
The following study report should be submitted to TGA:
- Study 20190009 by 28 March 2028
- Sponsor to conduct and submit results of a multi center, randomised clinical trial to further characterise serious adverse events, including gastro intestinal toxicity and compare the safety and efficacy of sotorasib 960 mg daily versus a lower daily dose in patients with locally advanced or metastatic, KRASG12C mutated, non-small cell lung cancer who have received at least one prior systemic therapy.
- Sponsor to conduct and submit results of a hepatic impairment clinical trial to determine a safe and appropriate dose of sotorasib in patients with moderate and severe hepatic impairment. Design and conduct the trial in accordance with the Food and Drug Administration (FDA) guidance for industry titled 'Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling'.
- Sponsor to conduct and submit results of a clinical drug interaction study to assess the effect of concomitant sotorasib administration on the systemic exposure of Breast Cancer Resistance Protein (BCRP) transporter substrates. Refer to FDA guidance for industry for additional details: 'Clinical Drug Interaction Studies - Cytochrome P450 Enzyme and Transporter Mediated Drug Drug Interactions.'
- Sponsor to conduct and submit results of clastogenicity studies (to be assessed by an in vitro or in vivo clastogencity study, preferably by in vivo chromosome aberration assay) of impurities [Studies] 3379613, 3379620, 3368167, 3396902, 3412607, 3413168, 3422551, 3422536 and 3422547; these results will need to be submitted before full registration of sotorasib is granted.