A Phase 2 trial to evaluate the safety and efficacy of zimberelimab monotherapy, domvanalimab + zimberelimab, and domvanalimab + zimberelimab + etrumadenant in front-line non-small cell lung cancer.
Adenosine is a powerful immunosuppressive substance produced inside tumors as a result of rapid cancer cell turnover and, in some cases, in connection with certain anti-tumor interventions, such as chemotherapy and radiation.
The A2a/A2b receptors, expressed on the surface of immune cells, mediate the immunosuppressive effects of adenosine.
Etrumadenant is designed to maximally inhibit the adenosine-driven impairment of tumor-infiltrating lymphocytes (mainly CD8+ T cells and NK cells) and myeloid cells (dendritic cells, macrophages), mediated by A2a/A2b, respectively. A2bR is also upregulated by certain cancer cells, such as in prostate cancer and KRAS-mutated cancers. As a result, etrumadenant may uniquely block adenosine’s immunosuppressive and cancer cell-intrinsic effects.
Developed specifically for the oncology setting, etrumadenant achieves high penetration of tumor tissue, robust potency in the presence of high adenosine concentrations, and minimal shift in potency from non-specific protein binding. Etrumadenant has demonstrated a favorable clinical safety profile with a variety of combination regimens and exhibits pharmacokinetics/pharmacodynamics consistent with once-daily dosing.
Etrumadenant is currently being evaluated in several Phase 1b/2 studies across multiple indications.
A Phase 2 trial to evaluate the safety and efficacy of zimberelimab monotherapy, domvanalimab + zimberelimab, and domvanalimab + zimberelimab + etrumadenant in front-line non-small cell lung cancer.
A Phase 1b trial to evaluate the safety, tolerability, PK, PD, and clinical activity of etrumadenant + carboplatin + pemetrexed ± zimberelimab in EGFR mutant non-squamous non-small cell lung cancer.
A Phase 1b/2 trial to evaluate the efficacy and safety of etrumadenant-based treatment combinations in participants with metastatic castration-resistant prostate cancer.
A Phase 2 trial to evaluate the safety, tolerability, PK, and antitumor activity of multiple immunotherapy-based combinations including regorafenib + atezolizumab ± etrumadenant in participants with metastatic colorectal cancer refractory to first- and second-line therapies.
A Phase 1b trial to evaluate the safety, tolerability, PK, PD, and clinical activity of etrumadenant + mFOLFOX in participants with gastroesophageal cancer or colorectal cancer.
A Phase 1b/2 trial to evaluate the safety, tolerability, PK, and preliminary antitumor activity of multiple immunotherapy-based combinations including etrumadenant + nab-paclitaxel + gemcitabine + atezolizumab in participants with metastatic pancreatic ductal adenocarcinoma.
A randomized Phase 1b/2, open-label, multi-center platform study to evaluate the efficacy of etrumadenant (AB928)-based combinations in patients with metastatic colorectal cancer.
