Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Urogenital Diseases

Prostatic Neoplasms, Castration-Resistant

Genital Diseases

Prostatic Diseases

Genital Diseases, Male

Male Urogenital Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

All Drugs and Chemicals

Androgens

Hormones

Gedatolisib

Androgen Receptor Antagonists

Protein Kinase Inhibitors

Enzyme Inhibitors

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)

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)

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)

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

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.

Darolutamide

Genelle Brower, RN

Nadene Zack, MS

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.

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.

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

Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant 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)

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

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

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

Radiographic progression-free survival rates at 9 and 12 months and overall rPFS Overall Survival (OS) rate at 18 and 24 months

Spots Global Cancer Trial Database for urogenital diseases, male