Trametinib
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Trametinib: Choroideremia
One-Sentence Summary
Trametinib is a MEK inhibitor originally used to treat metastatic melanoma. The TxGNN model’s top-ranked prediction is Choroideremia, but this rests on a computational score alone, with 0 clinical trials and 0 publications supporting it.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Choroideremia |
| TxGNN Prediction Score | 0.9931 |
| Evidence Level | L5 (choroideremia); L2 (non-cutaneous melanoma) |
| Canada Market Status | Marketed (marketed DINs: 3 of 3) |
| Number of DINs | 3 (marketed: 3) |
| Recommended Decision | Hold (choroideremia); the melanoma-subtype predictions are better framed as research questions |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From the pharmacology records, trametinib inhibits MEK1 (MAP2K1) and MEK2 (MAP2K2) in the MAPK pathway. It is used for BRAF V600-mutant melanoma, and in combination with dabrafenib for other BRAF V600E-mutant cancers such as anaplastic thyroid cancer.
Choroideremia (rank 1): This is an X-linked retinal degeneration caused by loss of function of the CHM gene, which impairs Rab prenylation. No clear mechanistic link to MEK inhibition is evident. The high score is a model output only, and the prediction should be treated with scepticism.
Melanoma subtypes (ranks 2–10): Most of the other predictions are melanoma variants. Here the mechanistic rationale is much stronger:
- Non-cutaneous melanoma (mucosal, uveal, acral) often has MAPK pathway activation (BRAF, NRAS, NF1). MEK inhibition is plausible, though uveal melanoma is usually GNAQ/GNA11-driven and less BRAF-dependent.
- Superficial spreading melanoma is frequently BRAF V600-mutant, but it overlaps with the approved melanoma indication, so it is largely not true repurposing.
- Acral lentiginous melanoma has fewer BRAF V600 mutations, which weakens the rationale.
- Lentigo maligna melanoma has more NRAS/NF1/KIT alterations, so trametinib is plausible in NRAS/NF1-mutant disease.
- CDK4-linked melanoma acts on the cell cycle, so the link to MAPK inhibition is indirect.
Clinical Trial Evidence
Choroideremia has no registered clinical trials. The table below covers the trials listed for non-cutaneous melanoma (rank 2), the most evidence-rich prediction.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02296112 | Phase 2 | Completed | 9 | Trametinib in melanoma with BRAF non-V600 mutations; directly relevant but very small |
| NCT04439292 | Phase 2 | Active, not recruiting | 44 | NCI-MATCH Subprotocol H: dabrafenib + trametinib in BRAF V600-mutant tumours, tumour-agnostic |
| NCT05907304 | Phase 1 | Active, not recruiting | 86 | Naporafenib + trametinib in RAS Q61X solid tumours |
| NCT02974725 | Phase 1 | Terminated | 241 | LXH254 combinations (including trametinib) in KRAS/BRAF-mutant NSCLC or NRAS-mutant melanoma |
| NCT02872259 | Phase 1/2 | Completed | 74 | BGB324 with pembrolizumab or dabrafenib/trametinib in advanced melanoma; trametinib is part of the backbone |
| NCT02410863 | Phase 2 | Terminated | 10 | Biopsy-driven targeted therapy optimisation in BRAF-mutant melanoma; too small to be informative |
| NCT03944356 | N/A | Completed | 232 | Observational study of adjuvant dabrafenib + trametinib in clinical practice |
| NCT03340506 | Phase 4 | Recruiting | 100 | Roll-over study for long-term safety of dabrafenib and/or trametinib |
| NCT07440290 | Phase 2/3 | Recruiting | 30 | DETERMINE platform trial: dabrafenib + trametinib in BRAF V600-mutant cancers |
| NCT05275374 | Phase 1/2 | Not yet recruiting | 221 | XP-102 with trametinib in BRAF V600-mutant solid tumours; no data yet |
Most of these trials test trametinib in combination or across tumour types, so they do not isolate its effect in non-cutaneous melanoma.
Literature Evidence
No literature was identified for choroideremia. The table below covers the melanoma-subtype predictions, where only indirect evidence exists.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40853557 | 2025 | Review | JAMA | General review of cutaneous melanoma (epidemiology and management); indirect evidence |
| 31361915 | 2020 | Case report/Review | Clin Exp Dermatol | Two BRAF-mutated conjunctival melanomas of epithelioid type, treated with vemurafenib, plus literature review |
| 31747798 | 2019 | Case report/Review | J Investig Med High Impact Case Rep | Lacrimal sac melanoma in 15 Japanese patients (case report and review) |
| 41209431 | 2026 | Case report | Oncol Lett | Combined BRAF/MEK inhibition for BRAF-mutant melanoma brain metastases in pregnancy |
| 37756677 | 2025 | Case report | Retin Cases Brief Rep | Rapid resolution of choroidal metastasis of cutaneous melanoma after combined targeted therapy |
| 42583475 | 2026 | Case report | Ann Med Surg | Early metastatic BRAF V600E-mutant melanoma without a known primary lesion |
All of this is case-level or general review evidence. No RCTs were found.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02409658 | MEKINIST | Not specified | Not specified |
| 02409623 | MEKINIST | Not specified | Not specified |
| 02539993 | MEKINIST | Not specified | Not specified |
All three licences are valid single-ingredient products.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (MEK1/2 kinase inhibitor), not a conventional cytotoxic agent |
| 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: 17 records were retrieved. Fifteen are interactions rated Moderate:
- Fostamatinib
- Elagolix
- Apalutamide
- Brigatinib
- Dabrafenib
- Encorafenib
- Isavuconazonium
- Lasmiditan
- Midostaurin
- Sarecycline
- Enzalutamide
- Erdafitinib
- Gilteritinib
- Idelalisib
- Tucatinib
The other two records are target-pharmacology entries (MEK1 and MEK2), not interactions.
Package insert warnings and contraindications were not available, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, choroideremia)
Rationale:
- Choroideremia is supported only by a model score, with no trials, no literature, and no plausible mechanistic link between MEK inhibition and CHM-related Rab prenylation defects.
- The remaining melanoma subtypes are supported only by case reports or general reviews, and several are mostly covered by the existing indication.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada (a blocking gap for safety screening)
- Detailed mechanism of action data (MOA)
- Trials or studies that isolate trametinib’s effect in specific non-cutaneous melanoma subtypes, stratified by mutation (BRAF, NRAS, NF1, GNAQ/GNA11)
- Any preclinical or mechanistic evidence for MEK inhibition in choroideremia, before this prediction is pursued further
- Approved indication text for the Canadian MEKINIST licences, to confirm the label scope
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.