Arcus Biosciences announced that quemliclustat, an investigational small-molecule CD73 inhibitor, was granted orphan drug designation by the U.S. Food and Drug Administration to treat pancreatic cancer.

Orphan drug designation is intended to support the development and evaluation of new treatments for rare diseases affecting fewer than 200,000 people in the United States. 

This designation qualifies sponsors for incentives, including tax credits for qualified clinical trials, exemption from user fees, including New Drug Application (NDA), and a potential seven years of market exclusivity after approval.

Quemliclustat is an investigational, potent and selective small molecule CD73 inhibitor that is being co-developed in collaboration with Gilead Sciences. CD73 is the primary enzymatic producer of immunosuppressive adenosine in the tumor microenvironment, and high CD73 expression is associated with significantly poorer prognosis in several tumor types.

In January 2024, Arcus presented results from the Phase 1 ARC-8 study, which showed no new safety signals and a median overall survival (OS) of 15.7 months in a pooled analysis of all patients treated with the 100mg quemliclustat-based regimens. The median OS exceeded the historical benchmark data for chemotherapy alone, including patients with liver metastasis, which accounts for more than half of all pancreatic cancers. 

Based on the ARC-8 results, Arcus initiated PRISM-1, a registrational Phase 3 study to evaluate quemliclustat plus gemcitabine/nab-paclitaxel chemotherapy versus gemcitabine/nab-paclitaxel chemotherapy alone in approximately 610 patients with pancreatic ductal adenocarcinoma (PDAC) who have not been previously treated in the metastatic setting. The study is expected to be fully enrolled this year.

PRISM-1 is a global, randomized, double-blind, placebo-controlled, multi-center Phase 3 study that will enroll approximately 610 patients with treatment-naïve metastatic PDAC. Participants will be randomized 2:1 between quemliclustat plus gemcitabine/nab-paclitaxel chemotherapy and gemcitabine/nab-paclitaxel chemotherapy plus placebo arms. 

The primary endpoint is overall survival (OS), and secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety.