Novel Compound (Omaveloxone) Restores Immune Response in Patients With Melanoma
Novel compound may restore immune response in patients with melanoma, according to a study presented at the ESMO Immuno Oncology Congress 2017.
“Checkpoint inhibitors are a standard of care immunotherapy for
metastatic melanoma. However, many patients do not respond because myeloid derived
suppressor cells (MDSCs), a type of inhibitory cell, are present in the tumor
microenvironment.
“In animal studies, omaveloxolone inhibited MDSCs and restored
immune activity,”MDSCs produce reactive nitrogen radicals that
alter the receptors on the surface of the tumor to hide it from cytotoxic
lymphocytes that kill tumor cells. Omaveloxolone inhibits MDSC activity,
suppresses reactive nitrogen radicals, and restores anti-tumor immune
responses. Administering omaveloxolone with checkpoint inhibitors may improve
the antitumor response of these immunotherapies.”
This open-label, multicenter, phase IB trial investigated the
safety and efficacy of omaveloxolone in combination with the checkpoint
inhibitors ipilimumab or nivolumab. The study included 30 patients with
unresectable or metastatic melanoma, of whom seven were naïve to checkpoint
inhibitors and 23 had prior checkpoint inhibitor treatment.
The overall response rate was 57 percent in checkpoint inhibitor-naïve
patients and 17 percent in those with prior exposure. Median time to response
was 19 weeks. There were no serious adverse events related to omaveloxolone and
it was well-tolerated in combination with ipilimumab or nivolumab.
These findings suggest that omaveloxolone may overcome resistance
to checkpoint inhibitors,” Patel noted. “Omaveloxolone in combination with
checkpoint blockade had activity in both naïve and checkpoint inhibitor
refractory melanoma patients.
“This is one of the first studies to demonstrate a meaningful
response rate in the checkpoint inhibitor refractory melanoma population.
Further dose escalation and dose expansion studies are underway as well as
translational tissue-based experiments to clarify the impact of this treatment
combination.”
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