A Phase 1 clinical trial for people with advanced solid cancers has dosed its first participant with Agenus‘ investigational antibody, AGEN1223, a therapy designed to improve immune system efficiency in cancer patients.
The open-label trial (NCT04156100) is currently recruiting up to 40 patients with advanced solid tumors in whom other treatments have failed. Recruitment is occurring at two locations in the U.S.: the HonorHealth Research Institute and the University of Southern California Norris Comprehensive Cancer Center.
Goals of the trial are to determine the safety, tolerability, maximum tolerated dosage, how the body handles the therapy (pharmacokinetics), and the observed effect of the compound on the body (pharmacodynamics).
This will be accomplished using what is called an accelerated titration model for the first two groups of patients treated. This means that each patient will receive a higher concentration of AGEN1223 each time they take the treatment until significant toxicity is reported.
Using the standard 3+3 model, patients will then be divided into groups of three and receive treatment in three different dosages.
The therapy will be infused into the vein once every three weeks, with evaluations performed at specific times throughout the study, including tumor assessments every six weeks. Enrolled patients will receive treatment for two years, unless the disease progresses or the dose received causes a toxic response in the patient.
AGEN1223 is a bispecific antibody, meaning that it is able to recognize and attach itself to two highly specific targets simultaneously. The two targets of AGEN1223 are found in regulatory T-cells (or Tregs) that are specifically in close proximity of a tumor.
The natural function of Tregs is to block immune activity. Therefore, the goal of AGEN1223 is to remove these cells from the tumor location to increase immune system activity around the tumor.
Because they lack the proteins targeted by AGEN1223, Tregs outside the tumor and effector T-cells — those with the ability to kill tumors directly — are largely spared from destruction. Rather, AGEN1223 stimulates the activity of these effector T-cells and recruits them to tumors.
“AGEN1223 is a novel bispecific antibody designed to selectively deplete specific immune-suppressive cells called regulatory T cells. The ability to deplete these cells in the tumor microenvironment may be an important treatment advantage for patients with cancer,” Anna Wijatyk, MD, head of clinical development at Agenus, said in a press release.
In the trial, AGEN1223 will first be tested alone, but Agenus also has plans to test a combination of AGEN1223 with its PD-1 inhibitor, balstilimab, later this year. Balstilimab belongs to a class of immune checkpoint inhibitors, which block signals from cancer cells that suppress immune T-cell activity.
“AGEN1223 is designed to eliminate the escape pathways that tumors use to continue to grow beyond multiple lines of therapy, including anti-PD-1 therapy,” Wijatyk said. “We believe that AGEN1223, due to its design to both selectively deplete intratumoral Tregs while sparing peripheral Tregs and to activate effector immune cells, represents an important novel therapy and promising combination agent for patients with aggressive tumors.”
At the same time, Agenus is conducting another Phase 1 trial (NCT03860272) using balstilimab and another checkpoint inhibitor, AGEN1181, which targets the checkpoint molecule CTLA-4 protein. CTLA-4 inhibitors work to increase T-cell expansion. The first patient in that study was also dosed recently.