Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer

Phase 1

Recruiting

• Conditions: mCRPC (Metastatic Castration-resistant Prostate Cancer); Genital Diseases, Male; Prostatic Disease; Prostatic Neoplasms, Castration-Resistant; Urogenital Diseases, Male; Prostate Cancer
• Interventions: Drug: Gedatolisib; Drug: Darolutamide

• Registration Number: NCT06190899
• Lead Sponsor: Celcuity Inc

Brief Summary

This is a Phase 1/2, open-label, randomized, dose finding and dose expansion study to evaluate the safety, preliminary efficacy, and PK of gedatolisib in combination with darolutamide in subjects with mCRPC.

Detailed Description

This is a Phase 1/2, open-label, randomized, dose finding and dose expansion study to evaluate the safety, preliminary efficacy, and pharmacokinetics of gedatolisib, a pan-PI3K/mTOR inhibitor, in combination with darolutamide, a next-generation androgen receptor inhibitor, in patients with metastatic castration-resistant prostate cancer following progression on a next-generation androgen receptor inhibitor. The aim of the Phase 1 portion of the study is to evaluate dose limiting toxicities and to determine the recommended Phase 2 dose. The aim of the Phase 2 portion of the study is to further assess the safety and preliminary efficacy of the drug combination.

Study Timeline

• Study First Submitted: 2023-12-13
• Study Start: 2024-01-01
• Study First Submitted QC: 2024-01-02
• Study First Posted: 2024-01-05
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-19
• Last Update Posted: 2025-03-21
• Primary Completion: 2025-11
• Study Completion: 2027-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1 Arm 1	Gedatolisib	Arm 1 - 120 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)
Phase 1 Arm 1	Darolutamide	Arm 1 - 120 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)
Phase 1 Arm 2	Darolutamide	Arm 2 - 180 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)
Phase 2	Darolutamide	The recommended Phase 2 dose (RP2D) of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)
Phase 1 Arm 2	Gedatolisib	Arm 2 - 180 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)
Phase 2	Gedatolisib	The recommended Phase 2 dose (RP2D) of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Primary Outcome Measures

Name	Time	Method
Phase 1: Assessment of the safety and tolerability of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer (mCRPC)	Cycle 1, Day 1 to end of safety follow up (each cycle is 28 days and safety follow up will continue until 30 days after last dose of study medication)	Type, incidence, severity (as graded by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0), seriousness, and relationship to study medications of adverse events (AEs) and any laboratory abnormalities
Phase 1: Identification of the recommended Phase 2 dose (RP2D) of gedatolisib in combination with darolutamide in mCRPC	Through Phase I completion, an average of 1 year.	Incidence of dose-limiting toxicities (DLTs) and AEs graded according to NCI CTCAE v5.0
Phase 2: Assessment of the antitumor activity of gedatolisib in combination with darolutamide in each arm as demonstrated by radiographic progression-free survival (rPFS) by arm	6 months	Radiographic progression-free survival rate at 6 months as measured by the Kaplan-Meier (K-M) method and assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with modifications as specified in Prostate Cancer Working Group 3 (PCWG3) criteria

Secondary Outcome Measures

Name	Time	Method
Assessment of the preliminary efficacy of gedatolisib in combination with darolutamide by arm	9 and 12 months post Cycle 1 Day 1 (each cycle is 28 days); 18 and 24 months post Cycle 1 Day 1 (each cycle is 28 days)	Radiographic progression-free survival rates at 9 and 12 months and overall rPFS Overall Survival (OS) rate at 18 and 24 months

Trial Locations

Locations (13)

Institut Catala d'Oncologia; 🇪🇸 Barcelona, Spain

Hospital Clinic Barcelona; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Instituto Valenciano de Oncología; 🇪🇸 Valencia, Spain

Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospita; 🇬🇧 Cambridge, United Kingdom

Royal Marsden NHS Foundation Trust; 🇬🇧 Sutton, United Kingdom

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France