Clinical trial · Interventional
Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma
A Phase III, Randomised, Open-label Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to the BRAF Inhibitor Vemurafenib in Subjects With Unresectable (Stage IIIc) or Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma
NCT01597908CI-TRIAL-00050274COMBI-vcompletedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This was a two-arm, open-label, randomized, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy with vemurafenib.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Melanoma | Melanoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Dabrafenib | Drug | Dabrafenib | ALIAS |
| Trametinib | Drug | Trametinib | ALIAS |
| Vemurafenib | Drug | Vemurafenib | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Dabrafenib plus Trametinib
- description
- BRAF inhibitor plus MEK inhibitor
- interventionNames
- Drug: Dabrafenib
- Drug: Trametinib
- type
- ACTIVE_COMPARATOR
- label
- Vemurafenib
- description
- BRAF inhibitor
- interventionNames
- Drug: Vemurafenib
Primary outcomes (1)
- measure
- Overall Survival (OS)
- timeFrame
- From the date of randomization until date of death due to any cause (up to approximately 6 years)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Key Inclusion Criteria: * \>= 18 years of age * Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma * Measurable disease according to RECIST 1.1 * Women of childbearing potential with negative serum pregnancy test prior to randomisation * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Adequate baseline organ function Key Exclusion Criteria: * Any prior use of a BRAF or MEK inhibitor * Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed * History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer) * Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed) * Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for \>= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for \>= 12 weeks, and are asymptomatic with no corticosteroid requirements for \>= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for \>= 4 weeks prior to randomisation * History or evidence of cardiovascular risk (LVEF \< LLN; QTcB \>= 480 msec; blood pressure or systolic \>=140 mmHg or diastolic \>= 90 mmHg which cannot be controlled by anti-hypertensive therapy) * History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
References
Publications (5)
- DERIVEDSchadendorf D, Robert C, Dummer R, Flaherty KT, Tawbi HA, Menzies AM, Banerjee H, Lau M, Long GV. Pyrexia in patients treated with dabrafenib plus trametinib across clinical trials in BRAF-mutant cancers. Eur J Cancer. 2021 Aug;153:234-241. doi: 10.1016/j.ejca.2021.05.005. Epub 2021 Jul 2. PMID 34225229
- DERIVEDRobert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, Chiarion Sileni V, Schachter J, Garbe C, Bondarenko I, Gogas H, Mandala M, Haanen JBAG, Lebbe C, Mackiewicz A, Rutkowski P, Nathan PD, Ribas A, Davies MA, Flaherty KT, Burgess P, Tan M, Gasal E, Voi M, Schadendorf D, Long GV. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med. 2019 Aug 15;381(7):626-636. doi: 10.1056/NEJMoa1904059. Epub 2019 Jun 4. PMID 31166680
- DERIVEDLong GV, Grob JJ, Nathan P, Ribas A, Robert C, Schadendorf D, Lane SR, Mak C, Legenne P, Flaherty KT, Davies MA. Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol. 2016 Dec;17(12):1743-1754. doi: 10.1016/S1470-2045(16)30578-2. Epub 2016 Nov 16. PMID 27864013
- DERIVEDGrob JJ, Amonkar MM, Karaszewska B, Schachter J, Dummer R, Mackiewicz A, Stroyakovskiy D, Drucis K, Grange F, Chiarion-Sileni V, Rutkowski P, Lichinitser M, Levchenko E, Wolter P, Hauschild A, Long GV, Nathan P, Ribas A, Flaherty K, Sun P, Legos JJ, McDowell DO, Mookerjee B, Schadendorf D, Robert C. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial. Lancet Oncol. 2015 Oct;16(13):1389-98. doi: 10.1016/S1470-2045(15)00087-X. PMID 26433819
- DERIVEDRobert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin AM, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015 Jan 1;372(1):30-9. doi: 10.1056/NEJMoa1412690. Epub 2014 Nov 16.