The open-label study (ACTRN12618000003279) will evaluate the safety, tolerability, pharmacokinetics — how a medicine behaves in the body — and preliminary signs of effectiveness of the two immune checkpoint inhibitors.
Researchers also will seek an optimal combination dose and schedule, which will be further evaluated in an expansion group of patients who suffer from inoperable cervical cancer and who have relapsed after receiving platinum-based chemotherapy.
The trial launched in December 2017 in Australia and recently completed enrollment into the first group.
“Speedy advancement of combination trials with our proprietary CTLA-4 and PD-1 antibodies is key to our strategy of commercializing our I-O agents. In addition, we believe both agents are crucial for combinations with our portfolio of proprietary immune oncology therapeutics,” Garo Armen, PhD, chairman and chief executive officer of Agenus, said in a press release. “Our antibodies were discovered, optimized, manufactured and advanced into the clinic at record speed because of our fully integrated capabilities.”
AGEN1884 and AGEN2034 are fully human antibodies designed to inhibit the activity of checkpoint proteins. These exist in healthy tissues, telling the immune system to leave them unharmed; but cancer cells evolved to present similar signals, allowing them to escape immune surveillance.
AGEN1884 targets the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) protein, found on cancer cells, while AGEN2034 binds to a protein called the programmed death 1 (PD-1), which is present at the surface of immune cells.
While acting on different pathways, they are both meant to help the immune system do a better job at recognizing and fighting cancer. Similar antibodies, like Opdivo (nivolumab), Keytruda (pembrolizumab), and Yervoy (ipilimumab) already are approved to treat cancer patients.
AGEN1884 and AGEN2034 were developed by Agenus in collaboration with Ludwig Cancer Research, 4-AntibodyAG, and Recepta Biopharma. Preclinical studies with monkeys have confirmed the synergy and effectiveness of combining both drugs, the company showed at the American Association for Cancer Research 2017 annual meeting.
These molecules are now under non-exclusive access models so that other researchers can use them and develop better combinations for cancer patients.