FDA Grants Orphan Drug Designation to Quemliclustat in Pancreatic Cancer
Quemliclustat plus gemcitabine and nab-paclitaxel chemotherapy outperformed median OS benchmarks in patients with metastatic PDAC. The investigational small molecule CD73 inhibitor quemliclustat was granted orphan drug designation for the treatment of patients with pancreatic cancer by the FDA, according to a press release from the developer, Arcus Biosciences.
“The orphan drug designation indicates the importance of developing new treatment options for rare diseases like pancreatic cancer, which has the highest mortality rate of all major cancers, and which has seen few treatment advancements over the past 30 years,” stated Richard Markus, MD, PhD, chief medical officer at Arcus Biosciences, in the press release. “We expect the phase 3 PRISM-1 study NCT06608927 to be fully enrolled this year and, if positive, intend to quickly bring this new first-line treatment option to patients, with the goal of prolonging survival for those with metastatic pancreatic cancer.”
Results from the phase 1 ARC-8 trial (NCT04104672), which evaluated quemliclustat plus chemotherapy in those with advanced pancreatic cancer, were shared in January 2024.
In all patients (n = 122), the median overall survival (OS) was 15.7 months (95% CI, 12.4-20.9), the 12-month OS rate was 62.7%, and the 18-month OS rate was 42.8%. In those who received quemliclustat plus gemcitabine and nab-paclitaxel (n = 29), the median OS was 19.4 months (95% CI, 12.1-23.0), the 12-month OS rate was 72.3%, and the 18-month OS rate was 54.2%. In those who received quemliclustat and zimberelimab plus gemcitabine and nab-paclitaxel (n = 61), the median OS was 14.6 months (95% CI, 10.6-21.5), the 12-month OS rate was 60.9%, and the 18-month OS rate was 43.5%. In the pooled analysis of all who received 100 mg of quemliclustat and zimberelimab plus gemcitabine and nab-paclitaxel (n = 93), the median OS was 13.9 months (95% CI, 11.1-18.7), the 12-month OS rate was 59.6%, and the 18-month OS rate was 39.3%.
The investigators noted improvements over gemcitabine and nab-paclitaxel in benchmark trials such as the phase 3 MPACT trial (NCT00844649), which had a median OS of 8.5 months (95% CI, 7.9-9.5), the phase 3 NAPOLI-3 trial (NCT04083235), which had a median OS of 9.2 months (95% CI, 8.3-10.6), and the phase 3 CanStem111P trial (NCT02993731), which had a median OS of 11.7 months (95% CI, 10.7-12.7).
Regarding safety, any-grade treatment-related adverse events (TRAEs) occurred in 99.2% of patients; grade 3 or higher TRAEs occurred in 73.0%. Serious TRAEs and grade 5 TRAEs occurred in 27.9% and 4.1%. AEs led to dose reduction, dose delay, and study discontinuation in 53.3%, 75.4%, and 23.0%.
The global, randomized, double-blind phase 3 PRISM-1 trial will evaluate quemliclustat plus gemcitabine and nab-paclitaxel chemotherapy compared with placebo plus gemcitabine and nab-paclitaxel. The trial is intended to be fully enrolled by the end of 2025, with an expected enrollment of 610 patients who will be randomly assigned to one of the trial arms in a 2:1 ratio.
