Clinical trial · Interventional
Combined BRAF-Targeted Therapy & Immunotherapy for Melanoma
COMBAT 1: A Phase II Trial of Combined BRAF-Targeted Therapy and Immunotherapy for Melanoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): changes in available treatments for melanoma
Summary
Brief summary (as posted)
This research study is a Phase II clinical trial of an investigational combination of drugs (vemurafenib and aldesleukin) to learn whether the combination works in treating a specific cancer. While both vemurafenib and aldesleukin are approved by the FDA for the treatment of metastatic melanoma, the FDA has not yet approved the combination of vemurafenib and aldesleukin. Researchers have found that a large number of melanoma cells have mutations in the BRAF gene. It has been shown that vemurafenib blocks the effects of these mutations in the BRAF gene, and, as a result, may help to prevent cancer growth. Aldesleukin, also referred to as IL-2, is an immunotherapy drug administered via IV infusion that increases the growth of key cells within the immune system that are responsible for targeting cancer cells. Activating more of these key cells, called T-lymphocytes and natural-killer cells, leads to increased cancer cell death. The BRAF gene is located on a larger pathway called the MAPK pathway. Studies have shown that when a BRAF inhibitor, like vemurafenib is used to block the MAPK pathway, melanocytes, or cancer cells express more proteins on their surfaces, making them easier for T-lymphocytes and natural killer cells to recognize and kill them. This suggests that combining BRAF-targeted therapy with aldesleukin, which activates more of these white blood cells, can lead to an increase in the death of cancer cells. In this research study, the investigators are looking to see whether the combination of vemurafenib (a BRAF-inhibitor) combined with aldesleukin(an immunotherapy drug) work together to produce a better health outcome in people with metastatic melanoma.
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 (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Aldesleukin | Drug | Aldesleukin | ALIAS |
| Vemurafenib | Drug | Vemurafenib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment Arm
- description
- Oral vemurafenib 960 milligrams twice a day plus intravenous aldesleukin 600,000 IU/kg every eight hours to tolerance (maximum 14 doses) over five days on days 15-19 of cycle 1 and on days 1-5 of cycle 2. (A cycle is 28 days) The first course of treatment will consist of three 28-day cycles (12 weeks): 2 weeks of lead-in vemurafenib plus 3 weeks on IL-2 plus 7 weeks wait. A second course may be given at the discretion of the investigator, if there is evidence of tumor stability or regression.
- interventionNames
- Drug: Aldesleukin
- Drug: Vemurafenib
Primary outcomes (1)
- measure
- Progression Free Survival
- timeFrame
- 3 years
- description
- To assess the efficacy (as measured by progression-free survival (PFS)) of patients with metastatic melanoma with V600E mutation treated with the combination of vemurafenib and aldesleukin. Progression free survival is defined as the time between the first dose of study drug and the first occurrence of progression of disease or death from any cause. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v.1.1), as at least a 20% increase in the sum of the diameters of target lesions or the appearance of one or more new lesions.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Histologically confirmed metastatic or unresectable melanoma with V600E mutation * Measurable disease * May have received prior immunotherapy (excluding interleukin 2) * Life expectancy greater than 3 months * Recovered from effects of previous surgery and/or traumatic injury * Must agree to use effective contraception Exclusion Criteria: * Pregnant or breastfeeding * Psychological, familial or other conditions that could hamper compliance with protocol * Receiving other study agents * History of carcinomatous meningitis * Known active brain metastases * Have received a BRAF inhibitor * Uncontrolled intercurrent illness * HIV positive on antiretroviral therapy * History of a different malignancy within past 5 years (except cervical cancer in situ or basal/squamous cell carcinoma of the skin) * Active hepatitis B or C * Have received allogenic bone marrow transplant or organ transplant
References
Publications (1)
- DERIVEDMooradian MJ, Reuben A, Prieto PA, Hazar-Rethinam M, Frederick DT, Nadres B, Piris A, Juneja V, Cooper ZA, Sharpe AH, Corcoran RB, Flaherty KT, Lawrence DP, Wargo JA, Sullivan RJ. A phase II study of combined therapy with a BRAF inhibitor (vemurafenib) and interleukin-2 (aldesleukin) in patients with metastatic melanoma. Oncoimmunology. 2018 Feb 1;7(5):e1423172. doi: 10.1080/2162402X.2017.1423172. eCollection 2018. PMID 29721378