Study of ORIC-101 in Combination With Anticancer Therapy

NCT03928314 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 101-18101
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 12

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 nab-paclitaxel or other anticancer therapies when administered to patients with advanced or metastatic solid tumors.

Conditions

Solid Tumor

Keywords

GR antagonist; Glucocorticoid receptor antagonist

Outcome Measures

Primary Outcomes (2)

• Part I: Recommended Phase 2 Dose (RP2D)

  RP2D as determined by 3+3 dose escalation design

  12 months

• Part II: Objective Response Rate (ORR)

  Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and assessed by Blinded Independent Central Review (BICR)

  18 months

Secondary Outcomes (12)

• Part I: Maximum plasma concentration (Cmax)

  28 Days

• Part I: Time of maximum observed concentration (Tmax)

  28 Days

• Part I: Area under the curve (AUC(0-t))

  28 Days

• Parts I and II: Number of Participants with Adverse Events

  36 months

• Parts I and II: Number of Participants with Abnormal Laboratory Values

  36 months

Other Outcomes (1)

• Parts I and II: Number of Participants with GR Expression by IHC

  36 months

Study Arms (2)

Dose Escalation (Part I)

EXPERIMENTAL

ORIC-101 dosed orally, once per day, for 5 or 7 days/week in combination with nab-paclitaxel (75 or 100 mg/m2 on Days 1, 8, and 15) of each 28-day cycle.

Drug: ORIC-101; Drug: Nab-paclitaxel

Dose Expansion (Part II)

EXPERIMENTAL

RP2D dose

Drug: ORIC-101; Drug: Nab-paclitaxel

Interventions

ORIC-101 DRUG

ORIC-101 once daily, 5 or 7 days/week, for 21 days of each 28-day cycle

Dose Escalation (Part I); Dose Expansion (Part II)

Nab-paclitaxel DRUG

75 or 100 mg/m2 Days 1, 8, and 15 of each 28-day cycle

Dose Escalation (Part I); Dose Expansion (Part II)

Eligibility Criteria

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

You may qualify if:

• Advanced or metastatic solid tumor, with the exception of neuroendocrine tumors that secrete adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH), for which no alternative effective standard therapy is available or for which standard therapy is considered unsuitable or intolerable
• Measurable disease (ie, presenting with at least one measurable lesion per RECIST 1.1)
• Radiographic evidence of a lesion that may be safely biopsied by core needle biopsy
• For patients with treated, stable CNS metastases that are asymptomatic: no evidence of progression for at least 4 weeks after CNS-directed treatment as determined by clinical examination and brain imaging. Patients must not require steroids
• ECOG performance status 0 or 1
• Life expectancy of at least 3 months
• Available archival FFPE tissue for submission to central laboratory
• Male: must agree to birth control requirements and Female: not pregnant, breastfeeding, and meets requirements regarding women of child-bearing potential
• Capable of giving signed informed consent
• Agreement and ability to undergo two on-study biopsies, as follows, through a procedure that is deemed to be clinically feasible and not carry significant risk:
• one pre-treatment tumor biopsy obtained prior to dosing; and
• one post-treatment tumor biopsy during Cycle 2

You may not qualify if:

• Any other current or active malignancy
• Grade 2 or higher peripheral neuropathy
• Known human immunodeficiency virus (HIV) infection
• Major surgery within 21 days prior to Cycle 1 Day 1 or incomplete recovery from adverse effects resulting from such procedure
• Females: history of unexplained vaginal bleeding in the 8 weeks prior to planned study treatment
• History of Cushing's syndrome or adrenal insufficiency
• Other concurrent serious uncontrolled medical, psychological, or addictive conditions that may interfere with planned study treatment or adherence to protocol
• Prior or current treatment with ORIC-101 or any other GR antagonist (eg, mifepristone, relacorilant)
• Current or requirement for chronic use of systemic corticosteroids with the exception of inhaled, topical, intraocular, intranasal, or intraarticular corticosteroids.
• Current or expected on-study treatment with specified strong CYP3A4 inhibitors or inducers
• Treatment with another investigational medicinal product (within 3 weeks prior to starting study treatment)
• Receiving any other anticancer therapy, radiotherapy, or herbal (alternative) medicines within 7 days prior to starting study treatment
• Use of hormone replacement therapy by females
• Current enrollment in any other therapeutic clinical study involving an investigational study treatment
• Presence of Hepatitis B surface antigen at screening

Sponsors & Collaborators

• ORIC Pharmaceuticals: lead

Study Sites (12)

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Colorado - PPDS

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists & Research Institute

Lake Mary, Florida, 32746, United States

Location

Florida Cancer Specialists & Research Institute

Sarasota, Florida, 34232, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Tennessee Oncology NASH - SCRI - PPDS

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research Centers - Medical City

Dallas, Texas, 75231, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• Chen CT, Khanna V, Kummar S, Abdul-Karim RM, Sommerhalder D, Tolcher AW, Ueno NT, Davis SL, Orr DW, Hamilton E, Patel MR, Spira AI, Jauhari S, Florou V, Duff M, Xu R, Wang J, Barkund SR, Zhou H, Pankov A, Kong W, Jahchan NS, Jackson EL, Sun JD, Junttila MR, Multani PS, Daemen A, Chow Maneval E, Munster PN. ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors. Cancer Res Commun. 2024 Sep 1;4(9):2415-2426. doi: 10.1158/2767-9764.CRC-24-0115.

  PMID: 39177285 DERIVED

MeSH Terms

Interventions

130-nm albumin-bound paclitaxel

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: Standard 3+3 dose escalation design, followed by dose expansion

Study Record Dates

• First Submitted: April 19, 2019
• First Posted: April 26, 2019
• Study Start: May 2, 2019
• Primary Completion: September 22, 2022
• Study Completion: December 4, 2023
• Last Updated: December 15, 2023

Record last verified: 2023-12

Locations

US (12)