Study of ORIC-101 in Combination With Enzalutamide

NCT04033328 | Terminated Phase 1 FDA Drug

• 1 other identifier: ORIC-101-02
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (7)

• Recommended Phase 2 Dose (RP2D)

  RP2D as determined by 3+3 dose escalation design

  12 months

• PSA Response Rate

  ≥50% decline from baseline at 8 weeks per Prostate Cancer Working Group 3 (PCWG3) criteria

  36 months

• PSA Progression

  From study start until PCWG3 criteria is met

  36 months

• Number of Participants with Adverse Events

  Safety and tolerability of ORIC-101 in combination with enzalutamide

  36 months

• Number of Participants with Abnormal Laboratory Values

  Safety and tolerability of ORIC-101 in combination with enzalutamide

  36 months

• Number of Participants with Abnormal 12-lead ECG

  Safety and tolerability of ORIC-101 in combination with enzalutamide

  36 months

• Number of Participants with Abnormal Vital Signs

  Safety and tolerability of ORIC-101 in combination with enzalutamide

  36 months

Secondary Outcomes (11)

• Maximum plasma concentration (Cmax)

  28 Days

• Minimum plasma concentration (Cmin)

  36 months

• Time of maximum observed concentration (Tmax)

  28 Days

• Area under the curve (AUC(0-24))

  28 Days

• Elimination half-life (T1/2)

  28 Days

Study Arms (2)

Dose Escalation

EXPERIMENTAL

ORIC-101 dosed orally, once per day in combination with enzalutamide (160 mg) of each 28-day cycle.

Drug: ORIC-101; Drug: enzalutamide 40 MG oral capsule [Xtandi]

Dose Expansion

EXPERIMENTAL

RP2D dose

Drug: ORIC-101; Drug: enzalutamide 40 MG oral capsule [Xtandi]

Interventions

ORIC-101 DRUG

ORIC-101 once daily in each 28-day cycle

Dose Escalation; Dose Expansion

enzalutamide 40 MG oral capsule [Xtandi] DRUG

160 mg once daily in each 28-day cycle

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Current treatment on another therapeutic clinical trial
• 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)
• History of Cushing's syndrome or adrenal insufficiency
• History or presence of CNS metastases
• History of seizures or condition that may predispose to seizures
• 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
• 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

Sponsors & Collaborators

• ORIC Pharmaceuticals: lead

Study Sites (3)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Abida W, Hahn AW, Shore N, Agarwal N, Sieber P, Smith MR, Dorff T, Monk P, Rettig M, Patel R, Page A, Duff M, Xu R, Wang J, Barkund S, Pankov A, Wang A, Junttila MR, Multani PS, Daemen A, Chow Maneval E, Logothetis CJ, Morris MJ. Phase I Study of ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Progressing on Enzalutamide. Clin Cancer Res. 2024 Mar 15;30(6):1111-1120. doi: 10.1158/1078-0432.CCR-23-3508.

  PMID: 38226958 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

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

Study Officials

• Pratik S. Multani, MD

  ORIC Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Model Details: Modified interval 3+3 dose escalation design, followed by dose expansion

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: July 26, 2019
• Study Start: October 28, 2019
• Primary Completion: November 22, 2022
• Study Completion: December 4, 2023
• Last Updated: December 15, 2023

Record last verified: 2023-12

Locations

US (3)