The open-label trial (NCT02963831) has already enrolled and evaluated the first group of patients, and is continuing to recruit as many as 78 patients at multiple centers across the U.S.
To be eligible, patients must have failed prior standard chemotherapy for either ovarian or colorectal cancer, and have failed to benefit or stopped responding to platinum-based chemotherapy, with no additional therapeutic options available.
“Patients diagnosed with advanced ovarian and colorectal cancers that have progressed on standard therapies have very few treatment options available to them,” Vanessa Lucey, PhD, director of the CRI Venture Fund and Clinical Accelerator, said in a press release.
“Under a unique partnership model, this study leverages the capabilities of two prominent nonprofit groups, accelerates innovation with top academic centers, and includes two different bio-pharmaceutical companies. This is the type of coordination and collaboration we need to accelerate progress for patients,” she said.
ONCOS-102 is a virus-based therapy that selectively infects and kills cancer cells, leaving healthy cells unharmed. It also carries in its genome a gene coding for GM-CSF, which is a protein that stimulates the immune system.
This suggested that in addition to killing cancer cells, ONCOS-102 was also increasing their sensitivity to immune checkpoint molecules targeting the PD-1 or PD-L1 proteins.
These findings provided a basis for testing a combination of ONCOS-102 and Imfinzi, a PD-L1 inhibitor already approved by the U.S. Food and Drug Administration for treating some lung and bladder cancers.
“Although checkpoint blockade antibodies have been remarkably effective in treating a variety of cancers, many patients fail to respond to these immunotherapies,” said Jonathan Skipper, Ludwig’s executive vice president for technology development. “Eliciting therapeutic responses in such patients through combination therapies is a top priority of Ludwig’s clinical research program, and a major objective of CRI’s as well.”
In the Phase 1 part of the trial, researchers will assess the tolerability and safety of ascending doses of ONCOS-102 to select the best dose for further evaluation.
The medicine will be injected into the abdominal cavity once a week for six weeks. Infinzi will be given either after ONCOS-102 treatment or at the same time as the therapy.
In Phase 2, investigators will examine the combination’s effectiveness including response rates, progression-free survival, and overall survival. In this group, Imfinzi will be given once every four weeks, starting in the third week.
“We have good reason to believe that combining checkpoint blockade with oncolytic virotherapy is a highly promising strategy to that end. We very much look forward to seeing the results of this trial,” Skipper said.