Clinical trial · Interventional
Testing Trametinib and Dabrafenib as a Potential Targeted Treatment in Cancers With BRAF Genetic Changes (MATCH-Subprotocol H)
MATCH Treatment Subprotocol H: Phase II Study of Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E or V600K Mutations (Excluding Melanoma, Thyroid Cancer, Colorectal Adenocarcinoma, and Non-Small Cell Lung Cancer)
- 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 phase II MATCH treatment trial identifies the effects of trametinib and dabrafenib in patients whose cancer has genetic changes called BRAF V600 mutations. Dabrafenib may stop the growth of cancer by blocking BRAF proteins which may be needed for cell growth. Trametinib may stop the growth of cancer cells by blocking MEK proteins which, in addition to BRAF proteins, may also be needed for cell growth. Researchers hope to learn if giving trametinib with dabrafenib will shrink this type of cancer or stop its growth.
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Lymphoma | Lymphoma | CURATED_BROADER | 0.78 |
| Advanced Malignant Solid Neoplasm | Malignant Solid Neoplasm | CURATED_BROADER | 0.78 |
| Hematopoietic and Lymphoid Cell Neoplasm | Hematopoietic and Lymphoid Cell Neoplasm | ONTOLOGY_EXACT | 0.98 |
| Refractory Lymphoma | Lymphoma | CURATED_BROADER | 0.78 |
| Refractory Malignant Solid Neoplasm | Malignant Solid Neoplasm | CURATED_BROADER | 0.78 |
| Refractory Multiple Myeloma | Multiple Myeloma | CURATED_BROADER | 0.78 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Dabrafenib Mesylate | Drug | Dabrafenib | ALIAS |
| Trametinib Dimethyl Sulfoxide | Drug | Trametinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment (dabrafenib, trametinib)
- description
- Patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- interventionNames
- Drug: Dabrafenib Mesylate
- Drug: Trametinib Dimethyl Sulfoxide
Primary outcomes (1)
- measure
- Objective Response Rate (ORR)
- timeFrame
- Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
- description
- ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol * Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol * Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment * Patients must have an ECHO or a nuclear study (multigated aquisition scan \[MUGA\] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) \< the institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be \> 50% for the patient to be eligible * Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria: * Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) * Treatment-refractory hypertension defined as a blood pressure of systolic \> 140 mmHg and/or diastolic \> 90 mmHg which cannot be controlled by anti-hypertensive therapy * Patients who previously received monoclonal antibody therapy (eg. ipilimumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib and dabrafenib Exclusion Criteria: * Patients with a diagnosis of metastatic melanoma from a cutaneous, acral, mucosal, or unknown primary site are excluded * Patients with a diagnosis of papillary thyroid cancer are excluded * Patients with a diagnosis of colorectal adenocarcinoma are excluded * Patients with a diagnosis of non-small cell lung cancer are excluded * Patients with a history of interstitial lung disease or pneumonitis are excluded * Patients must not have known hypersensitivity to dabrafenib and trametinib or compounds of similar chemical or biologic composition or to dimethyl sulfoxide (DMSO) * Patients must not have a history or current evidence/risk of retinal vein occlusion (RVO). An eye exam is required at baseline * Patients who previously received MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and pimasertib) will be excluded * Patients who previously received BRAF inhibitors (including, but not limited to, dabrafenib (Tafinlar), vemurafenib (PLX-4720) (Zelboraf), RAF265, LGX818 (encorafenib), RO5212054 (PLX3603), ARQ 736, XL281 (BMS-908662), CEP-32496, and the BRAF/MEK dual inhibitor (RO5126766) will be excluded * Patients with prior exposure to dabrafenib or trametinib on another treatment subprotocol of the MATCH trial are excluded * Current use of a prohibited medication. Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible. Current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded * Patients with a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded. An exception will be patients with cleared HBV and HCV infection which will be allowed on study * Patients with history of RAS mutation-positive tumors are not eligible regardless of interval from the current study * NOTE: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility
References
Publications (1)
- DERIVEDSalama AKS, Wang V, Macrae ER, Park JI, Chen HX, Gray RJ, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Armstrong DK, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Updated Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol H. JCO Precis Oncol. 2026 Jan;10:e2500338. doi: 10.1200/PO-25-00338. Epub 2026 Jan 14. PMID 41533998