“I am tremendously excited to announce that patient dosing in our innovative, adaptive Phase 1/1b trial is now underway with EOS100850, our unique and specific A2A receptor antagonist,” Michel Detheux, PhD, co-founder, president, and CEO of iTeos, said in a press release.
“We believe we have a potential best-in-class compound, which was carefully designed with differentiating features to maximize the therapeutic window,” Detheux added.
This binding prevents T-cells from multiplying, and reduces their ability to eliminate cancer cells. As an A2A receptor antagonist, EOS100850 prevents adenosine from binding the receptor, which then promotes T-cell activity.
A preclinical study has shown that EOS100850 potently inhibits the receptor in T-cells, even at very low doses, leading to an increased activity against tumor cells. The investigators note that the molecule does not enter the brain, where adenosine works as a neurotransmitter.
The ongoing open-label Phase 1/1b trial (NCT03873883) will evaluate the safety and efficacy of EOS100850 in adult patients with advanced solid tumors. The study also will assess the way the body breaks down and utilizes the molecule — known as pharmacokinetics or PK — and its mechanism of action in the body, called pharmacodynamics, or PD. EOS100850’s initial anti-tumor activity also will be monitored.
This flexible design study includes a dose-escalation part, in which a group of patients will receive increasing doses of the treatment. The results will enable researchers to recommend a safe, efficient dose of EOS100850 for future Phase 2 studies.
A dose-expansion study is planned to assess the efficacy of EOS100850 in patients with specific tumor types. The optimal EOS100850 dosage for this group will be based on the results of the dose-escalation study.
Enrollment for the study is ongoing at multiple clinical sites in the U.S., the U.K., and Belgium. A total 72 patients ages 18 and older with advanced solid cancers are expected to be enrolled in the trial. More information can be found here.
“The A2A pathway has emerged as one of the most exciting targets due to the emerging clinical evidence validating the important role adenosine plays in suppressing the immune response to cancer in the tumor microenvironment. EOS100850 addresses the therapeutic challenges found within this tumor microenvironment by achieving a higher degree of receptor inhibition with its PK/PD and non-brain penetrant profile and its ability to maintain potent efficacy despite increased levels of adenosine concentrations,” Detheux said.
“We are optimistic that EOS100850 can restore the immune response and may control cancer for patients in multiple indications,” he added.
Preliminary results of the Phase 1/1b study are expected by year’s end.
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