Combination of Gedatolisib and Darolutamide for Advanced Prostate Cancer

A Phase 1/2, Open-Label, Randomized, Dose Finding and Dose Expansion Study of Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This study is testing a new combination of two drugs, gedatolisib and darolutamide, to see if they can help men with advanced prostate cancer feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Celcuity Inc (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 13 sites (Detroit, Michigan and 12 other locations)
• Trial ID: NCT06190899 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 clinical trial evaluates the safety and preliminary efficacy of gedatolisib, a pan-PI3K/mTOR inhibitor, in combination with darolutamide, an androgen receptor inhibitor, in adult males with metastatic castration-resistant prostate cancer (mCRPC). The study is designed as an open-label, randomized trial that includes a dose-finding phase to identify the optimal dosage and a subsequent phase to further assess the treatment's effectiveness. Patients will be monitored for dose-limiting toxicities and overall response to the treatment regimen.

Who should consider this trial

Good fit: Ideal candidates for this study are adult males aged 18 and older with confirmed metastatic castration-resistant prostate cancer who have progressed after prior androgen receptor therapy.

Not a fit: Patients with prostate cancer that has a small cell component or those whose metastases are only visible on PSMA PET scans may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced prostate cancer that is resistant to standard therapies.

How similar studies have performed: Other studies involving PI3K/mTOR inhibitors in combination with androgen receptor inhibitors have shown promise, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria

1. Adult males ≥18 years of age
2. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without a small cell component and with \<10% neuroendocrine type cells
3. Subjects must have metastatic castration-resistant prostate cancer (mCRPC; i.e., developed progression of metastases following surgical castration or during medical androgen ablation therapy)
4. 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.
5. 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:

   5.1. 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.

   5.2. 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.
6. Continued primary androgen deprivation with luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist) if the subject has not undergone bilateral orchiectomy
7. Eastern Cooperative Oncology Group (ECOG) performance status score ≤1
8. Progression during treatment with one next-generation androgen receptor signaling inhibitor for metastatic disease (e.g., abiraterone, enzalutamide, apalutamide, darolutamide)
9. Completion of prior treatment with an androgen receptor inhibitor (ARi) ≥4 weeks before the first dose of the study drug
10. 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)
11. Adequate bone marrow, hepatic, renal and coagulation function

Exclusion Criteria

1. 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
2. Adenocarcinoma of the prostate with a small cell component, and with ≥10% neuroendocrine type cells
3. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (AKT) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
4. Prior treatment with chemotherapy or radiopharmaceutical therapy for mCRPC (except prior chemotherapy plus ADT for castration-sensitive disease, including docetaxel plus darolutamide).
5. Subjects with uncontrolled type 1 or type 2 diabetes

9\. 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

Where this trial is running

Detroit, Michigan and 12 other locations

• Barbara Ann Karmanos Cancer Institute — Detroit, Michigan, United States (Recruiting)
• Centre Jean Perrin — Clermont-Ferrand, France (Not_yet_recruiting)
• Institut Paoli-Calmettes — Marseille, France (Not_yet_recruiting)
• Centre Antoine Lacassagne — Nice, France (Not_yet_recruiting)
• Institut Gustave Roussy — Villejuif, France (Not_yet_recruiting)
• Hospital Clinic Barcelona — Barcelona, Spain (Recruiting)
• Institut Catala d'Oncologia — Barcelona, Spain (Recruiting)
• Hospital General Universitario Gregorio Maranon — Madrid, Spain (Not_yet_recruiting)
• Hospital 12 de Octubre — Madrid, Spain (Recruiting)
• Instituto Valenciano de Oncología — Valencia, Spain (Not_yet_recruiting)
• Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospita — Cambridge, United Kingdom (Not_yet_recruiting)
• University Hospital Southampton NHS Foundation Trust - Southampton General Hospital — Southampton, United Kingdom (Not_yet_recruiting)
• Royal Marsden NHS Foundation Trust — Sutton, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Genelle Brower, RN

Conditions mCRPC; Genital Diseases, Male; Urogenital Diseases, Male; Prostatic Disease; Prostatic Neoplasms, Castration-Resistant; Prostate Cancer; Gedatolisib; PI3K