A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition

Invest New Drugs. 2023 Jun;41(3):365-370. doi: 10.1007/s10637-023-01364-5. Epub 2023 Apr 25.


Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy.

Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110.

Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26-71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached).

Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration.

Keywords: BRAF inhibition; CSF1R inhibition; MEK inhibition; Melanoma.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase I

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Female
  • Humans
  • Male
  • Melanoma* / pathology
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf* / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf* / genetics
  • Skin Neoplasms* / pathology


  • BRAF protein, human
  • dabrafenib
  • Mitogen-Activated Protein Kinase Kinases
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf