Portage Biotech Inc. announced that it has dosed the first patient in its Phase 1a trial, ADPORT-601 (NCT04969315). The trial is evaluating Portage’s adenosine 2A receptor (A2AR) antagonist candidate, PORT-6, in patients with solid tumors including prostate cancer, renal and non-small cell lung cancer. ADPORT-601 is an adaptive Phase 1a/1b trial evaluating the safety and efficacy of PORT-6 (A2AR).

The trial also plans to evaluate Portage’s adenosine 2B receptor (A2BR) antagonist (PORT-7) and integrate proprietary biomarkers to select patients with high A2A and A2B expression. This approach is expected to allow for customization of treatment for any given tumor type to identify patients that are more likely to respond and have potential to benefit most from treatment. A critical mechanism of cancer immune evasion is the generation of high levels of immunosuppressive adenosine within the tumor microenvironment (TME).

Research suggests that the TME has significantly elevated concentrations (100-500 fold) of extracellular adenosine. Engagement with adenosine receptors A2A and A2B triggers a dampening effect on the immune response, suppressing effector cell function and stabilizing immunosuppressive regulatory cells. Over-expression of the A2A and A2B receptors leads to poor prognosis in multiple cancers, including prostate cancer, colorectal cancer and lung adenocarcinoma, driven by a reduced ability to generate an immune response against the tumor.

These findings have made A2A and A2B high-priority targets for immunotherapeutic intervention. Portage is advancing four first-in-class adenosine antagonist which together represent the full suite of adenosine-targeting approaches and will enable a comprehensive exploration of how targeting the adenosine pathway could improve response in multiple cancer and non-cancer indications. The ADPORT-601 adaptive Phase 1a/1b study will explore Portage Biotech’s small molecule adenosine antagonists, PORT-6 and PORT-7, as monotherapies, in combination with one another and potentially in combination with other Portage assets.

Phase 1a will evaluate the safety of PORT-6 and PORT-7 both as monotherapy and in combination with immune checkpoint inhibitors, with the goal of identifying a recommended Phase 2 dose. Phase 1b is designed to explore PORT-6 and PORT-7 monotherapies in an enriched population and in randomized trials vs. standard of care.