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2017 ASCO Annual Meeting: Results from the biomarker-driven basket trial of RO51267 (CH5126766), a potent RAF/MEK inhibitor, in RAS- or RAF- mutated malignancies, including multiple myeloma (Abstract 2506)
The results of this trial were presented by Maxime Chénard-Poirier from the Royal Marsden Hospital in London in an oral abstract session at ASCO 2017 Annual Meeting in Chicago, Illinois. This presentation was part of the ‘Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics’ session on Saturday June 4th, 2017.
CH5126766 is a first-in-class MEK inhibitor, with a long half-life (an average of 60 hours). Based on this extended half-life, dosing frequencies of two or three times weekly were studied in a dose escalation trial of 22 patients. However, the maximum tolerated dose and frequency was 4 mg two times per week. The most commonly reported adverse events (AEs) included rash, CK elevation, blurred vision, diarrhea, mucositis, fatigue and nausea. The most common grade 3 or higher toxicity was skin rash, which was managed with topical treatment.
This agent shows much promise for treatment of many malignancies, including myeloma, since approximately 20% of myeloma patients are positive for KRAS and NRAS mutations. In-vitro, MEK inhibitors are active against myeloma cell lines regardless of RAS status.
Preliminary results:
- Study included 4 myeloma patients (pts)
- All pts had received prior therapy with proteasome inhibitors and immunomodulatory drugs
- Total 75% of pts had a history of autologous stem cell transplant (ASCT)
- n = 1 pt with KRAS- and NRAS- mutation demonstrated a partial response; therapy is ongoing
- n = 2 pts with KRAS-only mutation demonstrated stable disease
- n = 1 pt NRAS-only mutation demonstrated clinical relapse
- The patient with partial response (PR) had no high-risk cytogenetic features, had received three prior lines of therapy and two ASCTs
- PR was achieved with single agent CH5126766, without concomitant dexamethasone therapy
In summary, twice weekly scheduling is well-tolerated. Preliminary results suggest single agent MEK inhibition may have activity in relapsed/refractory multiple myeloma.
References