Ripretinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ripretinib: From Gastrointestinal Stromal Tumour (GIST) to Multiple Endocrine Neoplasia
One-Sentence Summary
Ripretinib is an oral switch-control tyrosine kinase inhibitor that targets KIT and PDGFRA, and it is used in advanced gastrointestinal stromal tumour (GIST). The TxGNN model predicts it may be effective for multiple endocrine neoplasia, but there are 0 clinical trials and 0 publications directly supporting this prediction. This is a model prediction only, and the mechanistic link is speculative.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Advanced gastrointestinal stromal tumour (GIST). The Singapore licence record contains no indication text, so this is based on the published literature compiled for this report. |
| Predicted New Indication | Multiple endocrine neoplasia |
| TxGNN Prediction Score | 98.84% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. From the literature, ripretinib is a broad KIT/PDGFRA switch-control kinase inhibitor. It blocks both primary and secondary activating mutations, and it is used in advanced GIST. It also inhibits other receptor tyrosine kinases, such as VEGFR2 and TIE2.
Multiple endocrine neoplasia (MEN) syndromes are driven mainly by RET gain-of-function (MEN2) or MEN1 loss-of-function. No direct ripretinib activity against RET or the menin pathway is documented in the data compiled for this report. The connection between GIST and MEN is therefore speculative. It rests on the general idea that kinase inhibition might affect neoplastic signalling, not on specific evidence.
The score is high, but it should be read as a hypothesis to test, not as evidence of efficacy.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for multiple endocrine neoplasia.
Note: Publications on ripretinib in GIST exist (for example, the Phase 3 INTRIGUE trial, PMID 38182785). They concern a different disease and do not support this predicted indication.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16769P | QINLOCK TABLET 50 MG | Tablet | Not listed in the licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (tyrosine kinase inhibitor), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The interaction screening identified 90 potential interacting drugs. Examples of major-level interactions are:
- Clarithromycin
- Cobicistat
Both are CYP3A4-related inhibitors. Examples of moderate-level interactions include:
- Aprepitant
- Dexamethasone
- Cimetidine
- Miconazole
- Clotrimazole
- Pioglitazone
- Rosiglitazone
- Repaglinide
- Canagliflozin
- Deferasirox
Pharmacokinetic studies in the literature also indicate that ripretinib exposure is sensitive to CYP3A4 and P-glycoprotein modulators.
For warnings and contraindications, please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on model score alone (Evidence Level L5). There are no clinical trials or relevant publications, and the mechanistic link to the RET and MEN1 drivers of MEN is speculative. The package insert safety data has not been obtained.
To proceed, the following is needed:
- Preclinical data showing ripretinib activity against RET or other MEN-relevant targets in appropriate cell or animal models
- Detailed mechanism of action data (MOA)
- The HSA package insert, including warnings and contraindications, for safety screening
- A literature and trial search specific to MEN
- A review of the other predicted indications, most of which have even weaker plausibility (for example, veterinary viral diseases and amenorrhea)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.