Celcuity Inc. has reported encouraging Phase 1 clinical trial results for its investigational combination therapy of gedatolisib and darolutamide in men with metastatic castration-resistant prostate cancer (mCRPC). The data, presented at the European Society of Medical Oncology (ESMO) Congress, showed a median radiographic progression-free survival (rPFS) of 9.1 months and a six-month rPFS rate of 67%.
Trial Design and Patient Population
The Phase 1 study enrolled 38 patients with mCRPC whose disease had progressed on prior treatment with a next-generation 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). Gedatolisib was administered once weekly for three weeks followed by one week off, with all patients receiving prophylactic treatment for stomatitis.
Among the enrolled patients, 61% had received one line of prior systemic therapy while 39% had received two or more lines of prior therapy. The data analysis utilized an August 15, 2025 data cut-off with a median follow-up duration of 9.0 months.
Efficacy Outcomes
The lower dose arm (120 mg gedatolisib) demonstrated superior efficacy compared to the higher dose arm. Patients treated with 120 mg gedatolisib achieved a six-month rPFS rate of 74% and median rPFS of 9.5 months. In contrast, the 180 mg gedatolisib arm showed a six-month rPFS rate of 61% and median rPFS of 7.4 months.
"The 67% six-month rPFS rate and median rPFS of 9.1 months 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.
Safety Profile
The combination therapy demonstrated a favorable safety profile with mostly low-grade treatment-related adverse events (TRAEs). No dose-limiting toxicities were observed in either treatment arm. The only Grade 3 TRAEs reported across both arms included rash (5.3%), stomatitis (2.6%), and pruritus (2.6%). Notably, no Grade 3 hyperglycemia was reported, and no Grade 4 or 5 TRAEs were observed. Importantly, no patients discontinued study treatment due to treatment-related adverse events.
Next Steps in Development
Celcuity is now enrolling patients in an amended Phase 1/1b portion of the clinical trial to determine the recommended Phase 2 dose (RP2D). The updated study design includes up to six patients in each of three arms treated with different doses. Following Phase 1 completion, up to 40 additional patients will be randomly assigned to up to four Phase 1b cohorts for dose optimization.
The Phase 2 dose expansion study will enroll up to 18 additional subjects to achieve approximately 30 subjects treated with the RP2D, with all patients receiving standard doses of darolutamide.
About Gedatolisib
Gedatolisib is a potent, pan-PI3K and mTORC1/2 inhibitor that comprehensively blocks the PAM pathway. Its mechanism of action and pharmacokinetic properties differentiate it from other currently approved and investigational therapies that target PI3Kα, AKT, or mTORC1 alone or in combination. The compound is also being evaluated in Phase 3 trials for hormone receptor-positive, HER2-negative advanced breast cancer.
