Florida Cancer Specialists & Research Institute in Fort Myers contributed to a Phase 1 clinical study demonstrating significant antitumor activity with setidegrasib, a first-in-class therapy targeting KRAS G12D mutations in lung and pancreatic cancers. The study results were published in the New England Journal of Medicine, with FCS Associate Director of Drug Development Judy Wang serving as a co-author. The research involved 203 patients with previously treated advanced solid tumors harboring KRAS G12D variants.
“These results signify a major milestone in oncology and first proof of concept for targeted KRAS G12D, a genetic mutation long considered difficult to treat,” said Cesar Augusto Perez, director of the Drug Development Unit at the Sarah Cannon Research Institute at FCS in Lake Nona. The KRAS G12D variant occurs in 5% of patients with non-small-cell lung cancer and represents the most common substitution variant in pancreatic ductal adenocarcinoma, occurring in 40% of patients. No targeted therapies directed against this variant are currently approved for clinical use.
Among the 76 patients who received setidegrasib at the 600-mg dose selected for Phase 2 studies, adverse events occurred during treatment in all patients, with events of grade 3 or higher in 42%. Treatment-related adverse events occurred in 93% of patients, with the most common being transient infusion-related reactions in 80% and nausea in 30%. Adverse events led to discontinuation in only 2 patients, demonstrating the therapy’s tolerability profile.
For the 45 patients with non-small-cell lung cancer who received the 600-mg dose, 36% achieved a partial response with a median progression-free survival of 8.3 months and an estimated 12-month overall survival of 59%. Among the 21 patients with metastatic pancreatic ductal adenocarcinoma who received the 600-mg dose as second- or third-line treatment, 24% had a response with a median progression-free survival of 3.0 months and median overall survival of 10.3 months. Of these pancreatic cancer patients, 67% received setidegrasib as third-line treatment.
“Meaningful achievements such as this reinforce that FCS continues to lead at the forefront of breakthroughs in cancer treatment drugs and therapies,” said Manish R. Patel, FCS Medical Director of Drug Development. Early-phase clinical studies are conducted at FCS Drug Development Units in Sarasota and Central Florida. The organization operates in partnership with Sarah Cannon Research Institute, one of the world’s leading oncology research organizations conducting community-based clinical trials.
FCS maintains more than 180 active clinical trials at any point in time, positioning it as part of a network that reaches more clinical trial patients than any single cancer center in Florida. The organization has operated for more than 40 years, providing patients with access to innovative therapies through its robust clinical research program. Many cancer drugs approved by the FDA over the past decade were accessible to patients at FCS through clinical trial participation before receiving approval.
The Phase 1 study’s primary objectives included evaluating the safety, pharmacokinetics, pharmacodynamics and antitumor activity of setidegrasib in patients with previously treated advanced solid tumors. Setidegrasib was administered intravenously once weekly at doses ranging from 10 to 800 mg. The study results have determined the dosing protocol for the upcoming Phase 2 study, marking the next step in this targeted therapy’s development for patients with KRAS G12D-mutated cancers.