Publication date: Jun 07, 2019
A UCLA-led research team has pinpointed a three-drug combination that could prove to be an effective new therapy for people with a specific type of advanced melanoma.
In clinical trials, it appeared not to cause the debilitating side effects that are caused by a combination of one targeted drug and an immunotherapy drug.
The researchers found that people with the melanoma survived longer without the cancer progressing or growing when they received a combination of two targeted inhibitors that block the BRAF mutation (dabrafenib and trametinib) and an immune checkpoint inhibitor drug (pembrolizumab) as the initial treatment for their disease.
Dr. Antoni Ribas, the paper’s senior author, a professor of medicine at the David Geffen School of Medicine at UCLA and director of the UCLA Jonsson Comprehensive Cancer Center’s Tumor Immunology Program The results of phase one and phase two clinical trials were published today in two papers in the journal Nature Medicine.
In the phase two trial, those who received the three-drug combination had progression-free survival — meaning that the disease did not worsen or progress — for an average of 16 months.
“Earlier attempts to combine a targeted agent with an immune checkpoint inhibitor as a double-combination therapy had debilitating side effects for patients, and it was just too toxic to continue testing, so we went back to the drawing board,” said Ribas, who is also the director of the Parker Institute for Cancer Immunotherapy Center at UCLA.
In the phase one trial, the scientists tested the three-drug combination for safety in 15 people with BRAF-mutated metastatic melanoma.
Half of the patients received the three-drug combination, and the other half received the two targeted drugs and a placebo instead of the immunotherapy drug.
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | infections |
| drug | DRUGBANK | Tropicamide |
| gene | UNIPROT | ARMC9 |
| gene | UNIPROT | AKR1A1 |
| gene | UNIPROT | BEST1 |
| gene | UNIPROT | BAD |
| drug | DRUGBANK | Spinosad |
| disease | MESH | relapse |
| drug | DRUGBANK | Nonoxynol-9 |
| gene | UNIPROT | MAP2K7 |
| disease | MESH | growth |
| pathway | BSID | Immune System |
| drug | DRUGBANK | Pembrolizumab |
| drug | DRUGBANK | Trametinib |
| drug | DRUGBANK | Dabrafenib |
| disease | DOID | cancer |
| disease | MESH | cancer |
| gene | UNIPROT | BRAF |
| gene | UNIPROT | SMIM10L2A |
| gene | UNIPROT | SMIM10L2B |
| pathway | BSID | Melanoma |
| disease | DOID | melanoma |
| disease | MESH | melanoma |
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