Dabrafenib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Dabrafenib: From Metastatic Melanoma to Non-Cutaneous Melanoma
One-Sentence Summary
Dabrafenib is a BRAF kinase inhibitor, originally used to treat metastatic melanoma. The TxGNN model predicts it may be effective for non-cutaneous melanoma (mucosal, uveal, conjunctival and similar types), with 8 clinical trials supporting this direction. These trials are mostly early-phase, mixed-tumour or access/roll-over studies, so the evidence is moderate and no study isolates non-cutaneous melanoma.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastatic melanoma (the Singapore licence entries contain no indication text) |
| Predicted New Indication | Non-cutaneous melanoma |
| TxGNN Prediction Score | 98.48% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Proceed with Guardrails |
Note on the top-ranked prediction: The highest-scoring prediction is choroideremia (98.63%). It has no clinical or literature support and no plausible mechanistic link to BRAF inhibition, so it is rated L5 / Hold. This report focuses on non-cutaneous melanoma, the highest-ranked prediction with meaningful evidence, and it is also the closest to the original indication.
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not currently available in the data compiled for this report. Based on known information, dabrafenib is a BRAF V600 kinase inhibitor, usually combined with the MEK inhibitor trametinib. Its efficacy in BRAF V600-mutant metastatic melanoma is established.
A subset of non-cutaneous melanomas (mucosal, uveal, conjunctival and others) carry BRAF V600 mutations. This maps directly onto dabrafenib's target. The mutation is less frequent than in cutaneous melanoma, so molecular selection (BRAF V600 positivity) would be essential.
Related melanoma subtypes also show BRAF-directed activity in case-level reports. These include BRAF-mutated conjunctival (epithelioid) melanoma, scrotal melanoma and eyelid melanoma. They support plausibility but not efficacy.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04439292 | Phase 2 | Active, not recruiting | 44 | NCI-MATCH Subprotocol H: dabrafenib + trametinib in BRAF V600E/K-mutant tumours (excluding melanoma, thyroid, colorectal and lung cancers); biomarker-driven and most relevant |
| NCT02872259 | Phase 1/2 | Completed | 74 | BGB324 combined with pembrolizumab or dabrafenib/trametinib vs standard treatment alone in advanced melanoma; signal is for the combination |
| NCT07440290 | Phase 2/3 | Recruiting | 30 | DETERMINE platform trial: dabrafenib + trametinib in BRAF V600-mutant rare cancers; no results yet |
| NCT02410863 | Phase 2 | Terminated | 10 | Biology-driven targeted therapy in BRAF-mutant metastatic melanoma; very small, low informational value |
| NCT03944356 | N/A | Completed | 232 | Non-interventional study of adjuvant dabrafenib + trametinib in melanoma; population mainly cutaneous |
| NCT03340506 | Phase 4 | Recruiting | 100 | Roll-over study for long-term safety of dabrafenib/trametinib; safety data, not efficacy |
| NCT04418167 | Phase 1 | Suspended | 71 | ERK1/2 inhibitor JSI-1187 alone or with dabrafenib in MAPK-mutant solid tumours; indirect |
| NCT05585320 | Phase 1/2a | Active, not recruiting | 209 | IMM-1-104 (MEK1/2 inhibitor) in RAS/MAPK-activated solid tumours; indirect |
| NCT02416232 | N/A | No longer available | N/A | Trametinib access study in BRAF V600E/K-positive cutaneous melanoma; no efficacy information |
Literature Evidence
No publications were compiled for non-cutaneous melanoma. For related melanoma subtypes, the compiled literature is limited to case reports and reviews:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38590555 | 2024 | Review | Adv Ophthalmol Pract Res | Personalised and immunotherapy approaches in periocular (extraocular) cancers (eyelid melanoma) |
| 40853557 | 2025 | Review | JAMA | General review of cutaneous melanoma; no subtype-specific data |
| 31361915 | 2020 | Case report/review | Clin Exp Dermatol | Two BRAF-mutated bulbar conjunctival epithelioid melanomas treated with BRAF inhibitor (vemurafenib) and literature review |
| 33872566 | 2021 | Case report | Can J Urol | Metastatic primary scrotal melanoma (BRAF V600E) treated with oncogene-targeted therapy |
| 26710785 | 2015 | Cohort/molecular profiling | Mol Biol (Mosk) | Driver mutation spectrum (BRAF, NRAS, KIT) differs across melanoma subtypes |
| 31747798 | 2019 | Case report/review | J Investig Med High Impact Case Rep | Lacrimal sac melanoma in 15 Japanese patients |
| 42583475 | 2026 | Case report | Ann Med Surg | Early metastatic BRAF V600E melanoma without a known primary lesion |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14831P | TAFINLAR Hard Capsule 75 mg | Capsule | Not stated in the compiled data |
| SIN14830P | TAFINLAR Hard Capsule 50 mg | Capsule | Not stated in the compiled data |
| SIN17019P | TAFINLAR Dispersible Tablet 10 mg | Tablet, for suspension | Not stated in the compiled data |
All three licences are valid single-ingredient registrations, with no cancelled licences. Both forms are oral.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (BRAF kinase inhibitor), not conventional cytotoxic chemotherapy |
| 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 query returned 100 interacting drugs, and the 20 listed in the data compiled for this report are all rated Moderate. Examples include:
- Antidiabetic agents: acarbose, alogliptin, metformin, pioglitazone, chlorpropamide, acetohexamide
- Acid-suppressing agents and antacids: famotidine, ranitidine, cimetidine, aluminum hydroxide, calcium carbonate, magnesium oxide
- Corticosteroids: hydrocortisone, dexamethasone, betamethasone, triamcinolone
- Others: bupropion, aprepitant, clarithromycin, cisapride
Please refer to the package insert for other safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Dabrafenib's BRAF-inhibition mechanism directly applies to BRAF V600-mutant non-cutaneous melanoma, and Phase 2 and early-phase studies, including a biomarker-driven basket trial, support the direction. However, no study isolates non-cutaneous melanoma efficacy, and the supporting literature is limited to case reports and reviews, so any further work should be restricted to BRAF V600-positive patients.
To proceed, the following is needed:
- Package insert warnings and contraindications for the Singapore licences (currently missing, and a blocking gap for safety screening)
- Detailed mechanism-of-action data from DrugBank
- Non-cutaneous melanoma-specific results from NCT04439292 and NCT07440290 once available
- A BRAF V600 testing and patient-selection plan
- A review of the interacting drugs in this population
- Approved indication text for the Singapore licences, to confirm the original indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.