Phase 1b Study: Quemliclustat Regimens Extend Survival in Untreated Metastatic Pancreatic Cancer

Recent findings from a Phase 1b clinical trial, ARC-8, have indicated that the use of an experimental drug, quemliclustat, in combination with chemotherapy and potentially an anti-PD-1 antibody, zimberelimab, may significantly extend the survival of patients with untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). The ARC-8 study, a collaboration between Arcus Biosciences, Inc. and Gilead Sciences, Inc., has shown that the median overall survival for patients administered with 100 mg of quemliclustat-based regimens was 15.7 months, surpassing the historical benchmark for chemotherapy alone.

A post-hoc analysis revealed a 37% decrease in the risk of death and an improvement of 5.9 months in median overall survival for patients on the quemliclustat regimen compared to a Synthetic Control Arm® (SCA®), which consisted of patients treated with chemotherapy alone. The data, which will be presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, suggests that targeting CD73, an enzyme highly expressed on pancreatic cancer cells, with a small molecule inhibitor like quemliclustat, could enhance patient outcomes without a significant increase in toxicity.

The study included 122 patients with first-line mPDAC who received the 100mg dose of quemliclustat along with chemotherapy and, in some cases, zimberelimab. The data cut-off date was June 19, 2023. The results demonstrated a numerical advantage in median overall survival for the quemliclustat-based regimens over historical data for chemotherapy alone, which typically shows a median overall survival of around nine months.

The SCA was constructed by the Medidata AI team, who matched patients from previous studies that used gemcitabine/nab-paclitaxel in Phase 2 and 3 clinical trials for first-line metastatic pancreatic cancer. The matched SCA was created based on a pre-specified plan before the unblinding and analysis of overall survival data. The comparison indicated a longer survival for ARC-8 participants than the matched control group.

The most common adverse events were neutropenia and anemia, with five reported deaths, none of which were attributed to quemliclustat or zimberelimab by the study investigators. It's important to note that both drugs are still under investigation and have not been approved for any use globally.

Quemliclustat is a potent and selective CD73 inhibitor, which is believed to improve outcomes by blocking the production of adenosine, an immunosuppressive substance in the tumor microenvironment. By removing adenosine's effects, the activation of antitumor immune cells may be restored, leading to cancer cell death.

Pancreatic cancer is known for its aggressive nature and poor prognosis, with a 5-year survival rate of only 3% for those diagnosed in the metastatic stage. The majority of pancreatic cancers are adenocarcinomas, and chemotherapy has been the standard treatment for over 30 years with limited advancements.

Arcus Biosciences is a clinical-stage biopharmaceutical company that focuses on developing innovative cancer treatments. The company is committed to accelerating the development of novel therapies targeting well-defined biological pathways and exploring combinations that could potentially extend the lives of cancer patients.

The ARC-8 trial is an open-label, dose-escalation, and dose-expansion study designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of the combination of quemliclustat, zimberelimab, and chemotherapy in advanced pancreatic cancer patients. The trial's endpoints include safety, overall response rate, median overall survival, and progression-free survival. More details about the trial can be found on ClinicalTrials.gov.

Pancreatic cancer is diagnosed in the pancreas, an organ that aids digestion and regulates blood sugar levels. It is one of the most aggressive forms of cancer, with a low survival rate, especially when diagnosed at a late stage. The majority of pancreatic cancers are adenocarcinomas, which form in tissues that line certain internal organs and release digestive fluids.