Lack of Clinical Benefit Leads to End of Development for Etrumadenant in mCRPC

The development of etrumadenant (AB928) as a potential treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) will be discontinued after data from the phase 1/2 ARC-6 trial (NCT04381832) did not demonstrate a sufficient clinical benefit for etrumadenant plus zimberelimab (AB122) and docetaxel compared with docetaxel alone.¹

Although the study will continue to completion, further development of etrumadenant in mCRPC will be deprioritized, according to Arcus Biosciences.

Etrumadenant is a small-molecule, A2a/A2b adenosine receptor antagonist. Adenosine is an immunosuppressive substance generated in tumors through rapid cancer cell turnover and potentially in connection with chemotherapy or radiation. The A2a/A2b receptors are expressed on the surface of immune cells and could mediate the immunosuppressive effects of adenosine.²

The open-label, randomized ARC-6 trial evaluated etrumadenant-based combinations in patients at least 18 years of age with mCRPC. Patients in all cohorts were required to have an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate hematologic and end-organ function. Disease progression following prior androgen synthesis inhibitor therapy was required for patients treated with a docetaxel-containing regimen.³

For all patients, key exclusion criteria included prior immune checkpoint therapy, prior anticancer therapy within 2 to 4 weeks of first study treatment, prior allogeneic stem cell or solid organ transplant, brain metastases, and leptomeningeal disease. In the docetaxel arms, patients could not have had prior treatment with docetaxel, cabazitaxel (Jevtana), or other taxane chemotherapy, or active or a history of autoimmune disease or immune deficiency.

The combination of etrumadenant, zimberelimab, and docetaxel was evaluated in stage 1 of the study, and in stage 2, patients were randomly assigned to receive the combination or docetaxel alone. The study also included cohorts of patients being treated with the combination of etrumadenant, zimberelimab, and enzalutamide (Xtandi); etrumadenant and zimberelimab; etrumadenant, zimberelimab, and quemliclustat (AB680); etrumadenant and quemliclustat; etrumadenant and sacituzumab govitecan-hziy (Trodelvy); and etrumadenant, zimberelimab, and sacituzumab govitecan.

Overall response rate and the incidence of adverse effects (AEs) in stage 1 were the trial’s primary end points. Secondary end points included prostate-specific antigen response, radiographic response, disease control rate, pharmacokinetics, and the incidence of AEs in stage 2.

Enrollment has been completed for the phase 1/2 ARC-9 trial (NCT04660812) evaluating etrumadenant plus zimberelimab and chemotherapy for the second- or third-line treatment of patients with metastatic colorectal cancer, and data are expected in the first half of 2024.¹

References

1. Arcus Biosciences reports second-quarter 2023 financial results and provides a pipeline update. News release. Arcus Biosciences. August 7, 2023. Accessed August 9, 2023. https://investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2023/Arcus-Biosciences-Reports-Second-Quarter-2023-Financial-Results-and-Provides-a-Pipeline-Update/default.aspx
2. Adenosine pathway – etrumadenant. Arcus Biosciences. Accessed August 9, 2023. https://arcusbio.com/our-science/clinical-candidates/adenosine-pathway/etrumadenant/
3. Adenosine receptor antagonist combination therapy for metastatic castrate resistant prostate cancer (ARC-6). ClinicalTrials.gov. Updated August 2, 2023. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04381832