Vedanta Bioscience has started a Phase 1/2 trial to test its investigational oral microbiome therapy, VE800, in combination with the immune checkpoint inhibitor Opdivo (nivolumab) as treatment for certain advanced cancers.
VE800 is a collection of 11 bacterial strains normally present in the healthy human gut, selected for their ability to stimulate CD8 T-cells, which are able to kill cancer cells. The trial, which is now enrolling patients in the U.S., is part of a collaboration between Vedanta and Bristol-Myers Squibb.
“Despite unprecedented global investment in checkpoint inhibitors, there is still a major need for differentiated approaches to further enhance and expand responses in cancer,” Bernat Olle, PhD, co-founder and chief executive officer of Vedanta, said in a press release.
“The role the gut microbiota plays in influencing responses to immunotherapies has been ignored by previous approaches, so we are excited about the potential of microbiome modulation to open up an entirely new approach to cancer therapy,” he added.
The human gut microbiome — the natural, beneficial community of microbes living in the gut — is increasingly seen as a key factor determining a person’s susceptibility to certain diseases and responses to therapy.
Previous research has shown that specific bacterial strains of the gut microbiome may contribute to the effectiveness of immunotherapy, namely that of checkpoint inhibitors, in cancers such as advanced melanoma.
This suggests that people with different microbial composition may respond differently to cancer immunotherapies, and that modifying which microbes reside in the gut may enhance such responses.
VE800 is an investigational oral microbiome therapy made up of 11 bacterial strains that work together to activate tumor-killing CD8-positive T-cells. The bacterial strains are rare in the human microbiome, and an increase in their abundance — achieved through VE800 — represents a potential way to amplify their benefits.
In mouse models of colon cancer and melanoma, VE800 increased the number of these T-cells within tumors and amplified the effects of immune checkpoint inhibitors.
The open-label clinical study (NCT04208958), called CONSORTIUM-IO, is exploring the safety, tolerability, and clinical activity of VE800 in combination with Opdivo in people with advanced cancers.
Ongoing at clinical sites in the U.S., the first-in-human trial, is enrolling up to 111 patients with advanced melanoma, gastric cancer, gastroesophageal junction adenocarcinoma (a rare cancer of the esophagus), and microsatellite-stable colorectal cancer. For more information on contacts and locations, click here.
The trial’s main goals are to determine the combination’s safety and the proportion of patients responding to treatment. Secondary measures include duration of response, proportion of patients who draw some benefit from the treatment, the time to disease progression or death, and overall survival. Top-line results are expected in 2021.
“The ability of bacterial consortia to mediate immune activity, including potential anti-cancer activity, is an exciting area for investigation in indications with some of the highest unmet medical need,” said Hassane M. Zarour, MD, co-leader of the Cancer Immunology and Immunotherapy Program of the Hillman Cancer Center, University of Pittsburgh.
“We see enormous potential for this class of drugs to improve cancer patients’ outcomes,” added Zarour, who is also a member of Vedanta’s newly formed Immuno-Oncology Scientific Advisory Board.
Opdivo, marketed by Bristol-Myers Squibb, is an immune checkpoint inhibitor that works to prevent cancer cells from ‘shutting down’ the activity of immune cells, enabling the immune system to more effectively attack cancers. It is approved for many solid cancers and lymphoma, but not for the indications being tested in this trial.