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

NCT06190899 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CELC-G-201
• Study Type: interventional
• Target: 54
• Locations: 4 countries
• Sites: 13

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.

Conditions

mCRPC (Metastatic Castration-resistant Prostate Cancer); Genital Diseases, Male; Urogenital Diseases, Male; Prostatic Disease; Prostatic Neoplasms, Castration-Resistant; Prostate Cancer

Keywords

Gedatolisib; PI3K; Protein Kinase Inhibitors; mCRPC (metastatic castration-resistant prostate cancer); Darolutamide; Prostate Cancer; Prostatic Neoplasms, Castration-Resistant; Prostatic Disease; Urogenital Diseases, Male; Genital Diseases, Male

Outcome Measures

Primary Outcomes (3)

• Phase 1: Assessment of the safety and tolerability of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer (mCRPC)

  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

  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)

• Phase 1: Identification of the recommended Phase 2 dose (RP2D) of gedatolisib in combination with darolutamide in mCRPC

  Incidence of dose-limiting toxicities (DLTs) and AEs graded according to NCI CTCAE v5.0

  Through Phase I completion, an average of 1 year.

• 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

  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

  6 months

Secondary Outcomes (1)

• 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)

Study Arms (3)

Phase 1 Arm 1

EXPERIMENTAL

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)

Drug: Gedatolisib; Drug: Darolutamide

Phase 1 Arm 2

EXPERIMENTAL

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)

Drug: Gedatolisib; Drug: Darolutamide

Phase 2

EXPERIMENTAL

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)

Drug: Gedatolisib; Drug: Darolutamide

Interventions

Darolutamide DRUG

Darolutamide is a novel androgen receptor inhibitor that has been studied and received approval for treatment of patients with nonmetastatic CRPC and in metastatic hormone-sensitive prostate cancer.

Also known as: NUBEQA

Phase 1 Arm 1; Phase 1 Arm 2; Phase 2

Gedatolisib DRUG

Gedatolisib is a potent reversible inhibitor that selectively targets all Class I PI3K isoforms and mTOR.

Phase 1 Arm 1; Phase 1 Arm 2; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Adult Males
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males ≥18 years of age
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without a small cell component and with \<10% neuroendocrine type cells
• Subjects must have metastatic castration-resistant prostate cancer (mCRPC; i.e., developed progression of metastases following surgical castration or during medical androgen ablation therapy)
• Metastatic disease identified by conventional imaging: computed tomography (CT), magnetic resonance imaging (MRI), or technetium 99m-methyl diphosphonate (99mTc-MDP) bone scintigraphy. Measurable and non-measurable disease are allowed, but metastases visible only on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) will not be allowed for eligibility purposes.
• Progressive mCRPC based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with modifications as specified in Prostate Cancer Working Group 3 (PCWG3) criteria as defined by at least one of the following criteria:
• Prostate-specific antigen (PSA) progression defined as a minimum of 2 rising PSA levels with a minimum of a 1-week interval between each determination. A minimum PSA of 1.0 ng/mL is required for study entry.
• Soft-tissue progression defined as an increase ≥20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions. 5.3. Progression of bone disease (measurable disease) or 2 or more new bone lesions by bone scan.
• Continued primary androgen deprivation with luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist) if the subject has not undergone bilateral orchiectomy
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤1
• Progression during treatment with one next-generation androgen receptor signaling inhibitor for metastatic disease (e.g., abiraterone, enzalutamide, apalutamide, darolutamide)
• Completion of prior treatment with an androgen receptor inhibitor (ARi) ≥4 weeks before the first dose of the study drug
• At least 2 weeks beyond treatment with a targeted therapy or major surgery and at least 3 weeks beyond any other systemic anticancer therapy and/or radiation therapy, and resolution of all toxicities related to prior therapies or surgical procedures to baseline (except alopecia, Grade 1 peripheral neuropathy)
• Adequate bone marrow, hepatic, renal and coagulation function

You may not qualify if:

• History of malignancies other than adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥3 years
• Adenocarcinoma of the prostate with a small cell component, and with ≥10% neuroendocrine type cells
• Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (AKT) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
• Prior treatment with chemotherapy or radiopharmaceutical therapy for mCRPC (except prior chemotherapy plus ADT for castration-sensitive disease, including docetaxel plus darolutamide).
• Subjects with uncontrolled type 1 or type 2 diabetes
• \. Known and untreated, or active, brain or leptomeningeal metastases. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to randomization 10. History of clinically significant cardiovascular abnormalities 11. Gastrointestinal tract disease resulting in an inability to absorb oral medication as well as history of inflammatory bowel disease 12. Unable to swallow oral medication tablets/capsules

Sponsors & Collaborators

• Celcuity Inc: lead

Study Sites (13)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

NOT YET RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

NOT YET RECRUITING

Centre Antoine Lacassagne

Nice, 06100, France

NOT YET RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

NOT YET RECRUITING

Hospital Clinic Barcelona

Barcelona, 08036, Spain

RECRUITING

Institut Catala d'Oncologia

Barcelona, 08908, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

NOT YET RECRUITING

Hospital 12 de Octubre

Madrid, 28045, Spain

RECRUITING

Instituto Valenciano de Oncología

Valencia, 46009, Spain

NOT YET RECRUITING

Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospita

Cambridge, CB20QQ, United Kingdom

NOT YET RECRUITING

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

NOT YET RECRUITING

Royal Marsden NHS Foundation Trust

Sutton, SM25PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Genital Diseases, Male; Male Urogenital Diseases; Prostatic Diseases; Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms

Interventions

gedatolisib; darolutamide

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms

Study Officials

• Nadene Zack, MS

  Celcuity Inc

  STUDY DIRECTOR

Central Study Contacts

Genelle Brower, RN

CONTACT

844-310-3900; gbrower@celcuity.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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. The study is comprised of two phases: * Phase 1 Dose Finding (2 Parts) o Part 1: DLT evaluation and determination of tolerated doses * Part 2: Determination of RP2D * Phase 2 Dose Expansion

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: January 5, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

FR (4); GB (3); US (1); ES (5)