Novel compound restores immune response in patients with melanoma

December 8, 2017, European Society for Medical Oncology
Novel compound restores immune response in patients with melanoma
Credit: European Society for Medical Oncology

A 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," said lead author Dr Sapna Patel, Assistant Professor, Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, US. "However, many patients do not respond because myeloid derived (MDSCs), a type of inhibitory cell, are present in the tumour microenvironment."

"In animal studies, omaveloxolone inhibited MDSCs and restored immune activity," she continued. "Myeloid-derived suppressor cells (MDSCs) produce reactive nitrogen radicals that alter the receptors on the surface of the tumour to hide it from cytotoxic lymphocytes that kill tumour cells. Omaveloxolone inhibits MDSC activity, suppresses reactive nitrogen radicals, and restores anti-tumour immune responses. Administering omaveloxolone with inhibitors may improve the antitumour response of these immunotherapies."

This open label, multicentre, phase 1B 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 , of whom seven were naïve to checkpoint inhibitors and 23 had prior checkpoint inhibitor treatment.

The overall response rate was 57% in checkpoint inhibitor naïve patients and 17% 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.

Dr Patel said: "Our findings suggest that omaveloxolone may overcome resistance to checkpoint inhibitors. Omaveloxolone in combination with checkpoint blockade had activity in both naïve and checkpoint inhibitor refractory melanoma patients."

She added: "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."

Commenting on the study for ESMO, Dr Olivier Michielin, head of Personalised Analytical Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, said: "Omaveloxolone's novel mechanism of action is to block MDSCs, cells known to suppress the immune response. This study tested a new combination therapy in immuno oncology and found encouraging response rates with omaveloxolone plus ipilimumab or nivolumab in patients who were checkpoint inhibitor naïve or resistant. The combination was well tolerated and may address some of the immune escape mechanisms that limit the activity of current checkpoint blockade therapies."

Michielin added: "More data is needed before we can make a final call on whether there is a place, and where would the place be, for this combination in the current treatment portfolio. The next step should be a randomised trial to investigate whether omaveloxolone provides additional benefit when combined with the checkpoint blockade backbone, for example, comparing the efficacy of PD-1 blockade alone versus PD-1 blockade plus omaveloxolone."

Explore further: New immunotherapy combination shows promise for patients with advanced melanoma

More information: Abstract 5O_PR 'A phase 1b/2 study of omaveloxolone in combination with checkpoint inhibitors in patients with unresectable or metastatic melanoma' will be presented by Sapna Patel during a Proffered Paper Session on Friday 8 December, 08:30 to 10:30 CET in Room A. Annals of Oncology, Volume 28, 2017 Supplement 11. cslide.ctimeetingtech.com/esmo … nfcal/show/session/7

Related Stories

New immunotherapy combination shows promise for patients with advanced melanoma

April 5, 2017
Treatment with a combination of ipilimumab (Yervoy) and Coxsackievirus A21 (CVA21; Cavatak) led to durable responses in a number of patients with advanced melanoma, including some whose melanoma had progressed despite prior ...

Adding the IDO-pathway inhibitor indoximod to pembrolizumab improved the melanoma response rate

April 5, 2017
Adding the investigational immunotherapy indoximod to the FDA-approved immunotherapy pembrolizumab (Keytruda) increased the proportion of patients with advanced melanoma who responded to treatment compared with previously ...

Combination immunotherapy effective for advanced prostate cancer

March 9, 2017
Advanced prostate cancer resistant to castration therapy appears to respond well to a combination of immune checkpoint blockades and treatments that target certain immune-busting cells commonly associated with poor patient ...

Checkpoint inhibitors fire up different types of T cells to attack tumors

August 10, 2017
Cancer immunotherapies that block two different checkpoints on T cells launch immune attacks on cancer by expanding distinct types of T cell that infiltrate tumors, researchers from The University of Texas MD Anderson Cancer ...

Researchers show how a targeted drug overcomes suppressive immune cells

November 9, 2016
A Ludwig Cancer Research study shows that an experimental drug currently in clinical trials can reverse the effects of troublesome cells that prevent the body's immune system from attacking tumors. The researchers also establish ...

Drug combination shows better tolerance and effectiveness in metastatic renal cell cancer

July 26, 2017
A new cooperative research study including Norris Cotton Cancer Center's Lionel Lewis, MB BCh, MD, finds that nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses ...

Recommended for you

Week 34 of pregnancy reduces breast cancer risk: study

October 23, 2018
Women's bodies undergo a "striking" change during a specific week of pregnancy that can significantly reduce their risk of developing breast cancer later in life, scientists said Tuesday.

New combination treatment flips the switch on melanoma cells

October 23, 2018
Think of the protein BH3 like a finger that turns off a cancer cell survival switch. The problem is that most cancer cells have found ways to remove this "finger—commonly, by breaking the action of a gene called p53 that ...

New kind of compound shows early promise against prostate cancer

October 23, 2018
A new type of molecule blocks the action of genes that drive the growth of therapy-resistant prostate cancer, a new study finds.

Desperate & duped? GoFundMe means big bucks for dubious care

October 23, 2018
People seeking dubious, potentially harmful treatment for cancer and other ailments raised nearly $7 million over two years from crowdfunding sites, a study found.

Marker found for condition that causes numerous tumors

October 23, 2018
UT Southwestern researchers have made a major advance in uncovering the biology of how thousands of disfiguring skin tumors occur in patients troubled by a genetic disorder called neurofibromatosis type 1 (NF1). This scientific ...

Urban and rural rates of childhood cancer survival the same, study finds

October 23, 2018
Childhood and adolescent cancer survival in the United States does not vary by rural/urban residence at the time of diagnosis, finds a new study from the Brown School at Washington University in St. Louis.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.