The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2021 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The combination of the CD73 inhibitor AB680, zimberelimab, and chemotherapy demonstrated anticancer activity with a manageable safety profile in patients with metastatic pancreatic adenocarcinoma (PDAC), according to results of the phase 1/1b ARC-8 study presented at the 2021 Gastrointestinal Cancers Symposium.

Pancreatic cancers are known to express high levels of CD73, which has been associated with shorter progression-free survival. The aim of this study was to evaluate whether the combination of AB680 with the anti-PD-1 antibody zimberelimab and chemotherapy could improve pancreatic cancer outcomes.

In the ongoing, open-label ARC-8 trial (ClinicalTrials.gov identifier: NCT04104672), 19 patients with treatment-naïve, metastatic PDAC received AB680 plus zimberelimab and chemotherapy. Patients received doses of AB680 ranging from 25 mg to 100 mg. The primary end point was safety and tolerability. Secondary end points included AB680’s clinical activity and pharmacokinetics.

At baseline, the mean patient age was 64.1 years. Fifty-eight percent of patients were male. Seventy-four percent of patients were white, and 16% were Asian; race was not reported for 11% of patients. The majority of ARC-8 participants had an Eastern Cooperative Oncology Group performance status of 0 (74%).


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Among the 17 patients evaluable for efficacy, the objective response rate was 41%, which included all partial responses and compared “favorably with current standard-of-care chemotherapy,” according to Gulam Abbas Manji, MD, PhD, who presented the findings. There were 16 patients who remained on study treatment at the time of the data analysis (December 9, 2020).

Treatment-emergent adverse events (TEAEs) occurred in 95% of patients (18 of 19 evaluable patients) and were grade 3 or higher in 63%. The most common TEAEs included fatigue (68%), anemia (53%), alopecia (42%), diarrhea (42%), and neutropenia (42%). There was 1 dose-limiting toxicity (grade 2 autoimmune hepatitis) that resolved with treatment, enabling the patient to continue study treatment. There were no treatment discontinuations due to TEAEs.

The recommended dose for the expansion phase was tentatively selected as 100 mg of AB680. Enrollment in the cohort evaluating AB680 at 100 mg is ongoing.

 “Preliminary results from ARC-8 indicate that AB680, the first clinical-stage small-molecule CD73 inhibitor, in combination with standard-of-care chemotherapy plus zimberelimab has a manageable safety profile consistent with that expected for each agent alone and demonstrates early signals of clinical activity,” Manji concluded.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This clinical trial was supported by Arcus Biosciences, Inc.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO GI 2021 meeting by visiting the conference page.

Reference

Manji GA, Wainberg ZA, Krishnan K, et al. ARC-8: Phase 1/1b study to evaluate safety and tolerability of AB680 + chemotherapy + zimberelimab (AB122) in patients with treatment-naïve metastatic pancreatic adenocarcinoma. Poster presented at: 2021 Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract 404.