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Clin Cancer Res: bimetinib combined with ribocillin for NRAS-mutated melanoma

 Last Update: 2022-04-22
 Source: Internet
 Author: User

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Melanoma with NRAS mutation often has enhanced MAPK pathway signaling and cell cycle checkpoint dysregulation.
Therefore, the combination regimen of MEK inhibitor binimetinib and selective CDK4/6 inhibitor Ribociclib would be a promising strategy.
a reasonable joint solution
.

A combination regimen of the MEK inhibitor binimetinib and the selective CDK4/6 inhibitor Ribociclib would be a reasonable combination regimen
.

This is an open-label Phase Ib/II clinical trial to evaluate the initial activity and safety of ribocillin in combination with bimetinib in NRAS-mutated melanoma
.

The primary endpoint of Phase Ib is to determine the maximum tolerated dose of the combination regimen and the recommended Phase II dose (RP2D), and the primary endpoint of Phase II is the antitumor activity of the combination regimen (RP2D)

Between June 27, 2013, and November 10, 2016, a total of 102 patients were enrolled: 61 in the dose-escalation phase and 41 in the dose-expansion phase
.

In the first cycle of Phase Ib, 10 (16.

Progression-free survival in patients at different stages

In the phase II cohort (n=41), the overall response rate was 19.
5%
.

The response rate was 32.

The overall response rate was 19.

Treatment response in patients with different mutations

Common treatment-related toxicities were increased creatine phosphokinase, rash, edema, anemia, nausea, diarrhea, and fatigue
.

The results of the pharmacokinetic and safety analyses were consistent with those of the single-agent studies, suggesting that there was no interaction between the two drugs

In conclusion, the combination regimen of bimetinib and ribocillin can be safely used in NRAS-mutated melanoma patients with positive therapeutic activity
.

Cell cycle gene co-mutations may be used to screen patients who would benefit more from this regimen

The combination regimen of bimetinib and ribocillin can be safely used in patients with NRAS-mutated melanoma and has positive therapeutic activity .

Original source:

Martin Schuler, et al.

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