Study of ORIC-101 in Combination With Enzalutamide

Trial details

Who runs it

ORIC Pharmaceuticals

Trial code

NCT04033328

Record updated

2023. december 15.

Original description

The purpose of this study is to establish the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-101 in combination with enzalutamide (Xtandi®) when administered to patients with metastatic prostate cancer progressing on enzalutamide.Read full original descriptionShow less

An Open-Label Phase 1b Study of ORIC-101 in Combination With Enzalutamide in Patients With Metastatic Prostate Cancer Progressing on Enzalutamide

The purpose of this study is to establish the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-101 in combination with enzalutamide (Xtandi®) when administered to patients with metastatic prostate cancer progressing on enzalutamide.

Inclusion: Histologically or cytologically confirmed adenocarcinoma of the prostate; Metastatic prostate cancer currently being treated with enzalutamide (Xtandi®) 160 mg once daily plus surgical or ongoing chemical castration, with baseline testosterone level <50 ng/dL; Must have been on treatment with enzalutamide for at least 3 months prior to documented evidence of PSA progression defined as per PCWG3: minimum of 2 rising values (3 measurements) obtained a minimum of one week apart with the latest result being at least 2.0 ng/mL (or 1.0 ng/mL if PSA rise is the only indication of progression); Agreement and ability to undergo on-study core biopsies, as follows, through a procedure that is deemed to be clinically feasible and not carry significant risk:; one pre-treatment tumor biopsy obtained while on treatment with enzalutamide prior to enrollment on this study; and; one post-treatment tumor biopsy during Cycle 2; one end of treatment tumor biopsy (optional); ECOG performance status 0 or 1; Life expectancy of at least 3 months; Adequate organ function as defined by the following criteria:; ANC ≥1500 cells/mm3 (1.5 × 103 cells/mm3); Platelets ≥100,000 /µL (100 × 109 /L); Hemoglobin ≥9.0 g/dL (90 g/L); AST (SGOT) or ALT (SGPT) ≤2.5 × ULN, ≤5.0 × ULN for patients with liver metastases; Bilirubin ≤1.5 × ULN; patients with a known history of Gilbert's syndrome and/or isolated elevations of indirect bilirubin are eligible; QTcF ≤480 msec; Capable of giving signed informed consent.

Exclusion: No intervening therapy between enzalutamide treatment and enrollment on this study; Any other active malignancy, with the exception of adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 solid tumor malignancies without evidence of disease, or other solid tumors curatively treated with no evidence of disease for ≥5 years from enrollment; Prior or current treatment with ORIC-101 or any other GR antagonist (eg, CORT-125281, mifepristone, relacorilant); Prior chemotherapy in the metastatic castration-resistant prostate cancer setting; Prior treatment with a second-generation AR modulator (eg, apalutamide, abiraterone, darolutamide); Current (at C1D1) or requirement for chronic use of systemic corticosteroids with the exception of inhaled, topical, intraocular, intranasal, or intraarticular corticosteroids; Current (within 10 days prior to first dose of ORIC-101) or expected on-study treatment with specified strong CYP3A4 inhibitors or inducers; Receiving any other anticancer therapy, including radiotherapy within 21 days prior to C1D1. Patients must have recovered from all toxicities from prior anticancer therapies and/or radiotherapy; Major surgery within 21 days prior to C1D1 or incomplete recovery from adverse effects resulting from such procedure; History of Cushing's syndrome or adrenal insufficiency; History of seizures or condition that may predispose to seizures; Known human immunodeficiency virus (HIV) infection, unless patient is healthy and has a low risk of AIDS-related outcomes; Active Hepatitis B or C infection; Any other condition or circumstance (eg, clinical, psychological, familial, sociological, inability to swallow oral study drug) that, in the opinion of the investigator, may interfere with protocol compliance or contraindicates participation in the study; Current treatment on another therapeutic clinical trial; History or presence of CNS metastases.

ClinicalTrials.gov NCT04033328