Celcuity Inc. announced preliminary clinical data for gedatolisib, a multi-target PI3K/mTOR inhibitor, showing encouraging efficacy and safety results in two early-phase oncology trials. The biotechnology company reported a 66% six-month radiographic progression-free survival rate in metastatic castration-resistant prostate cancer and a 43% objective response rate in heavily pretreated HER2+ metastatic breast cancer patients.
Phase 1 Results in Metastatic Castration-Resistant Prostate Cancer
In the Phase 1 portion of the CELC-G-201 clinical trial, 38 patients with metastatic castration-resistant prostate cancer (mCRPC) received gedatolisib in combination with darolutamide, an approved androgen receptor inhibitor. Patients were randomly assigned to receive 600 mg darolutamide twice daily combined with either 120 mg gedatolisib (Arm 1) or 180 mg gedatolisib (Arm 2), administered once weekly for three weeks followed by one week off.
The preliminary efficacy and safety analyses showed a six-month radiographic progression-free survival rate of 66%. Notably, no patients discontinued treatment due to treatment-related adverse events, and no dose reductions were required for either gedatolisib or darolutamide. The safety profile was favorable, with no Grade 3 hyperglycemia reported and Grade 2-3 stomatitis occurring in only four patients (10.5%) - three with Grade 2 and one with Grade 3.
"The 66% six-month rPFS rate for this novel combination therapy compares favorably to published data for androgen receptor inhibitors in this setting," said Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity. "With no treatment-related discontinuations and less than 3% of patients experiencing Grade 3 stomatitis, we believe it is important to explore additional dose options for gedatolisib."
Dose Optimization Strategy
Based on pharmacokinetic data from other clinical trials suggesting a relationship between efficacy and dose levels, Celcuity amended the clinical trial protocol to explore additional doses. The company believes the optimal gedatolisib dose for mCRPC patients may not yet have been reached.
The amended Phase 1 portion will enroll up to six patients in each of three arms with different doses. Following Phase 1 completion, up to 40 additional patients will be randomly assigned to up to four Phase 1b cohorts to determine the recommended Phase 2 dose. The Phase 2 dose expansion study will enroll up to 18 additional subjects to achieve approximately 30 subjects treated with the recommended Phase 2 dose.
Phase 2 Results in HER2+ Metastatic Breast Cancer
In an investigator-sponsored Phase 2 clinical trial, 44 patients with HER2+/PIK3CA mutated metastatic breast cancer received gedatolisib plus standard doses of trastuzumab-pkrb. The patient population was heavily pretreated, with a median of four or more prior anti-HER2 therapies in the metastatic setting, and 86% of patients having received at least three prior anti-HER2 therapies.
Key efficacy results presented at the American Society of Clinical Oncologists meeting in June 2025 demonstrated an objective response rate of 43% among all enrolled patients. The median progression-free survival was 6.0 months (95% CI, 5.0-7.7), and median overall survival reached 24.7 months (95% CI; 17.3-NA).
The safety profile remained favorable, with no patients discontinuing gedatolisib due to treatment-related adverse events. Only one patient (2.3%) experienced Grade 3 hyperglycemia.
Clinical Significance and Future Development
"The 43% ORR reported in patients who received at least three prior lines of anti-HER2 treatment for their disease is very encouraging and compares favorably to published data for other available therapies in this group of patients," noted Dr. Gorbatchevsky. "The regimen was well tolerated, and no patients discontinued gedatolisib due to treatment-related AEs."
Gedatolisib is a potent, pan-PI3K and mTORC1/2 inhibitor that comprehensively blocks the PI3K/AKT/mTOR pathway by addressing all four class I PI3K isoforms and both mTOR complexes. Its mechanism of action and pharmacokinetic properties differentiate it from other approved and investigational therapies that target individual components of this pathway.
Ongoing Clinical Program
Celcuity is currently conducting multiple Phase 3 clinical trials with gedatolisib. The VIKTORIA-1 trial evaluates gedatolisib in combination with fulvestrant with or without palbociclib in patients with HR+/HER2- advanced breast cancer. The VIKTORIA-2 trial assesses gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- advanced breast cancer.
