Wednesday, May 27, 2015

ASCO 2015: New trial for melanoma brain mets!!! Ipi and Nivo, followed by Nivo alone (CheckMate 204)

A multi-center phase II open-label study (CheckMate 204) to evaluate safety and efficacy of Nivolumab (NIVO) in combination with ipilimumab (IPI) followed by NIVO monotherapy in patients with metastatic melanoma to the brain. J Clin Oncol 33, 2015. Margolin, Tawbi, Hodi, et al.

Brain mets develop in approx 50% of patients with metastatic melanoma.  (Median overall survival after diagnosis = 4 months.)  Nivo (a fully human IgG4 PD-1 checkpoint inhibitor antibody) and ipi (a fully human IgG1 CTLA-4 immune checkpoint inhibitor antibody) are each approved as monotherapy for advanced melanoma. In an already completed Phase II study, ipi showed some activity in patients with melanoma brain mets.  This study builds on that. It is anticipated that 50% of enrolled patients will have had stereotactic radiotherapy. Patients with measurable melanoma in extracranial sites and with asymptomatic brain mets will be included.  Patients with leptomemingeal disease, history of whole brain radiation, autoimmune disease, or steroids ongoing will be excluded.  Patients will be given Nivo 1mg/kg with ipi at 3mg/kg every three weeks for 4 doses, followed by nivo along at 3mg/kg every 2 weeks until progression or toxicity.  SRT for progression of a single brain met will be permitted.  

Here's the link to the study on

This trial is actively recruiting.  Sites so far in California and Pennsylvania.

This post includes links to prior studies where ipi and nivo demonstrated effect in the treatment of melanoma brain mets:  Ipi, nivo, the combo and radiation for melanoma brain mets

Given what we already know, this seems hopeful to me! - c


  1. Any idea what specifically is meant by, "Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions"? It seems like it could mean just cognitive or sensory deficits, or it could include symptomatic (extraordinary) fatigue and loss of appetite.

  2. Ultimately this decision/definition is up to the trial co-ordinator/researcher. However, it sounds as though patients enrolling need to have a normal neurologic exam with no overt neurologic seizures, one sided weakness, cognitive dysfunction, etc. Neither fatigue nor loss of appetite are specific neurologic signs.