Tepmetko
Registration timeline
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).
| Description | Date |
|---|---|
| Designation (Orphan) | 2 July 2021 |
| Determination (Provisional) | 2 July 2021 |
| Submission dossier accepted and first round evaluation commenced | 31 August 2021 |
| First round evaluation completed | 31 August 2021 |
| Sponsor provides responses on questions raised in first round evaluation | 31 August 2021 |
| Second round evaluation completed | 10 January 2022 |
| Delegate's Overall benefit-risk assessment and request for Advisory Committee advice | 1 November 2021 |
| Sponsor's pre-Advisory Committee response | 15 November 2021 |
| Advisory Committee meeting | 2 and 3 December 2021 |
| Registration decision (Outcome) | 11 January 2022 |
| Completion of administrative activities and registration on ARTG | 17 January 2022 |
| Number of working days from submission dossier acceptance to registration decision* | 88 |
*Statutory timeframe for standard applications is 255 working days
Tablet core: mannitol, colloidal anhydrous silica, crospovidone, magnesium stearate, microcrystalline cellulose
Film coating: hypromellose, lactose monohydrate, macrogol 3350, triacetin, iron oxide red, titanium dioxide
Treatment should be initiated and supervised by a physician experienced in the treatment of cancer.
The recommended dose of Tepmetko is 450 mg (two 225 mg tablets) orally once daily with food. Treatment should continue as long as clinical benefit is observed.
For further information refer to the Product Information.
Tepmetko (tepotinib) was approved for the following therapeutic use:
Tepmetko has provisional approval in Australia for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.
The decision to approve this indication has been made on the basis of overall response rate (ORR) and duration of response (DOR). Continued approval of this indication depends on verification and description of benefit in confirmatory trial(s).
- Tepmetko (tepotinib) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Tepmetko must include the black triangle symbol and mandatory accompanying text for the products entire period of provisional registration.
- 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 inversion 2.1 (dated 27 July 2021) of the Australia specific annex. The following study report should be submitted to TGA:
Study MS200095-0022, VISION, by date 1 November 2027
Further guidance for sponsors is available on the TGA website.
- The Tepmetko Core-risk management plan (RMP) (version 3.0 dated 10 May 2021; data lock point (DLP) 1 July 2020) and Australian specific annex version 2.1 (dated 27 July 2021) included with submission PM-2021-03109-1-4, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).
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 PSURs as described in the European Medicines Agency's Guideline on Good Pharmacovigilance Practices (GVP) Module VII-periodic safety update report (Rev 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.
- Submit final reports including datasets from clinical studies to confirm and further characterise the clinical benefit of tepotinib for the treatment of patients with non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations who are treatment-naïve and who have previously received systemic therapy, by providing a more precise estimation of the blinded independent central review-assessed overall response rate and duration of response.
- Conduct a drug interaction study to evaluate the effect of itraconazole on the single dose pharmacokinetics of tepotinib to assess the magnitude of increased drug exposure and determine appropriate dosing recommendations when tepotinib is administered concomitantly with a strong CYP3A4 and P-gp inhibitors.
- Conduct a drug interaction study to evaluate the effect of carbamazepine on the single dose pharmacokinetics of tepotinib to assess the magnitude of decreased drug exposure and determine appropriate dosing recommendations when tepotinib is administered concomitantly with a strong CYP3A4 inducer and moderate CYP2C8 inducer.