Oral MEK Inhibitor, Cobimetinib, Receives FDA Approval for Histiocytic Neoplasms


Cobimetinib is now an FDA-approved therapy for patients with histiocytic neoplasms.

Cobimetinib (Cotellic), an oral MEK inhibitor, has received FDA approval for the treatment of patients with histiocytic neoplasms, includingErdheim-Chester disease, Rosai-Dorfman disease, and Langerhans cell histiocytosis.1,2

The regulatory decision was based on data collected through a collaborative effort between Memorial Sloan Kettering (MSK) Cancer Center and Genentech. Data from the single-center, single-arm trial showed that at a median follow-up of 11.4 months (range, 0.2-36.8), cobimetinib elicited an objective response rate (ORR) of 76.9% (n = 20; 95% CI, 56.4%-91.0%) by PET and 46.2% (n = 12; 26.6%-66.6%) by RECIST criteria in 26 enrolled patients.

“The approval of cobimetinib represents the collective hard work of several years of investigation by many MSK researchers. There have been tremendous advances in the field of rare cancers as a result of research and trials conducted at MSK, and this approval is an excellent example of a practice-changing outcome,” Eli L. Diamond, MD, principal investigator of the trial, neurooncologist, and neurologist at MSK, stated in a press release. “There has always been an unmet need for patients with histiocytosis, and we are thrilled that with this approval, these patients will now have access to a viable treatment option.”

The trial enrolled adult patients with histologically confirmed histiocytic neoplasms of any mutational status. Notably, those with documented BRAF V600E mutations were permitted if they were unable to access a BRAF inhibitor or if they discontinued a BRAF inhibitor because of toxicity.

All participants had multisystem disease, recurrent or refractory disease, or single-system disease that was determined to be unlikely to benefit from conventional treatments, based on best available evidence.

Of the 26 patients enrolled to the trial, 4 had Langerhans cell histiocytosis, 4 had Rosai-Dorfman disease, 13 had Erdheim-Chester disease, 2 had xanthogranuloma, and 3 had mixed histiocytosis. The median age was 50.5 years (range, 18-79); 65% (n = 17) were male and 85% were White. The majority of patients (n = 20), had BRAF V600E wild-type disease and 6 had BRAF V600–mutated disease.

Study participants were administerd cobimetinib at a once-daily dose of 60 mg as part of a 21-days-on/7-days-off schedule in a 28-day cycle.

Best ORR (BORR) served as the main efficacy outcome for the trial. Other clinical outcomes of interest comprised duration of response (DOR) and BORR maintained on 2 occasions at least 4 weeks apart.

Additional data showed that the median time to response with cobimetinib was 2.0 months (range, 0.2-17.3) and the median DOR was 31 months (range, 2-31).

“Until now, no standard therapy has existed for the 50% of histiocytosis patients without the BRAF V600E mutation,” Omar Abdel-Wahab, MD, hematologic oncologist and director of the Center for Hematologic Malignancies at MSK, added in the press release. “The research pioneered at MSK has led to a viable treatment option for adult patients who harbor this mutation. Looking ahead, we are working on advancing treatment options for pediatric patients with histiocytosis as we have done in adults.”


  1. FDA approves oral MEK inhibitor cobimetinib for histiocytic neoplasms, research led by Memorial Sloan Kettering Cancer Center. News release. Memorial Sloan Kettering Cancer Center. November 1, 2022. Accessed November 2, 2022. https://bit.ly/3TZQPzv
  2. Cotellic. Prescribing information; Genentech; 2022. Accessed November 2, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206192s005lbl.pdf

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