WashU Medicine Physician-Scientists at Siteman Cancer Center Developing New Combination Therapy to Treat Metastatic Melanoma

The approach could potentially treat multiple cancer types, researchers say

WashU Medicine researchers at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, have developed a promising combination therapy for treating an aggressive form of melanoma. The early-phase research, led by George Ansstas, MD, David Y. Chen, MD, PhD, and Naresha Saligrama, PhD, appears in the Journal of Clinical Investigation.

The new therapy combines two commercially available drugs, tailmogene laherparepvec (also known as T-VEC) and binimetinib to treat patients with NRAS-mutated melanoma, a type of melanoma that is highly aggressive and occurs in up to 25% of patients diagnosed with cutaneous melanoma.

T-VEC, a genetically modified herpes virus, is already FDA-approved as a local therapy for the treatment of unresectable advanced melanoma. It was the first oncolytic virus therapy in the U.S. when it was approved in 2015. However, even though the modified virus can kill injected tumor cells, it doesn’t produce a strong enough immune response throughout the body on its own. Binimetinib is a MEK inhibitor that blocks the activity of MEK1 and MEK2 proteins to treat patients with NRAS-mutated melanoma. Currently, binimetinib is approved only in patients with two different types of cancer, BRAF-mutated melanoma and BRAF-mutated non-small cell lung cancer.

Early-phase research at Siteman investigated the use of T-VEC and binimetinib as a combination therapy in seven NRAS-mutated melanoma patients. Six patients achieved a complete response as compared to only two out of seven patients responding when treated with T-VEC alone.

“T-VEC works by replicating in cancer cells, causing them to burst, thereby stimulating the body’s immune response,” Ansstas said. “We have found that by combining T-VEC with binimetinib, we induced an exceptional clinical response in a small cohort of patients diagnosed with NRAS-mutated melanoma who participated in our early-phase trial.”

The findings point toward binimetinib’s role in amplifying T-VEC’s ability to kickstart the immune system and broaden the overall effectiveness of the immune response in patients. 

“The fact that we already have two commercially available therapeutics means that we can escalate the speed at which we move from early phase into larger clinical trials to test the dual therapy,” Ansstas said.

Patients diagnosed with NRAS-mutated melanoma currently are given immunotherapy as a standard first-line treatment. Other options include targeted therapies to slow tumor growth and other combination therapies in clinical trials. Now that there have been promising results in the early trial conducted at Siteman, the WashU Medicine researchers say larger, multicenter studies are needed to validate the T-VEC/binimetinib combination as a new option for treatment of NRAS-mutated melanoma.

“Once this observation is validated, we will expand our investigation to additional tumor types, as this mechanistic approach has the potential to be effective across multiple cancer types,” Ansstas said.