With $3M grant from Stand Up to Cancer, UCLA researcher to advance understanding of how a promising new combination therapy could overcome melanoma resistance to immunotherapy

Clinical study could potentially lead to improved patient outcomes compared to current standard of care
UCLA melanoma research pioneer Dr. Antoni Ribas

Dr. Antoni Ribas, director of the UCLA Jonsson Comprehensive Cancer Center’s Tumor Immunology Program and a professor of medicine at the David Geffen School of Medicine, has received a $3 million grant from Stand Up to Cancer to study the factors that shape how metastatic melanoma responds to a promising new drug combination therapy. By advancing the understanding of how patients respond to this therapeutic approach, the research has the potential to profoundly change the way the melanoma and other cancers are treated.

Stand Up To Cancer, under its SU2C Catalyst program, provides grants to researchers to conduct clinical trials and correlated translational research across a variety of cancers. The focus of SU2C Catalyst clinical trials is to study drugs used by themselves or in combination with other therapies as well as standard-of-care treatments, with the goal to improve outcomes for people with the disease. The SU2C Catalyst program also significantly expedites the process of going from ideas to contracts to trials, compared to traditional investigator-initiated studies.

As one of ten SU2C Catalyst clinical trial projects launched by Stand Up to Cancer, Ribas will lead the research entitled, “Reversing primary anti-PD-1 resistance with ipilimumab and nivolumab.”

Nivolumab and pembrolizumab are current standard first-line therapies for patients with metastatic melanoma. However, a majority of patient’s melanoma tumors are resistant to these treatments, and there is an urgent need to understand the mechanisms of how these tumors evade immune response and to better identify patients who will and will not respond to this therapy.

The study will test if patients whose melanoma did not respond to the front-line treatment could respond to the addition of ipilimumab, another immune checkpoint inhibitor. The two drugs, each blocking a different immune checkpoint, in effect release the brakes that limit the immune system’s response to cancer and allow it invade tumors and attack melanoma cells. However, side effects increase significantly. Therefore, this study would use this more toxic combination only in patients who may be more likely to need it because they had not benefitted from the less toxic single agent therapy.

“I am extremely grateful to receive this generous recognition of our research by Stand Up to Cancer,” Ribas said. “We have the potential to determine if the combination of two immune checkpoint inhibitors can reverse resistance to the single agents. I am very excited that this trial will better define which patients should receive the combination immunotherapy.”

An estimated 70,000 new cases of melanoma are diagnosed in the United States annually, and 8,000 people will eventually die of the disease each year.

Ribas’ clinical trial will be conducted through the SWOG melanoma committee, a network of researchers funded by the National Cancer Institute that design and conduct cancer clinical trials, thereby bringing the protocol to the smaller community hospitals and practices in addition to the participation of large academic centers.