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Study of ORIC-101 in Combination With Anticancer Therapy

Trial Status: Active

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.

Inclusion Criteria

  • PDAC: Advanced or metastatic PDAC previously treated with and progressed on a fluoropyrimidine-based regimen and a taxane-containing chemotherapy regimen (eg, gemcitabine + nab-paclitaxel). Pancreatic neuroendocrine tumors, lymphoma of the pancreas, acinar pancreatic cancer, or ampullary cancer are not eligible.
  • Ovarian Cancer: Advanced or metastatic high grade serous or endometrioid epithelial ovarian, primary peritoneal, fallopian tube cancer or ovarian carcinosarcoma, previously treated with and progressed on a taxane-containing chemotherapy regimen; clear cell, mucinous and borderline histologic subtypes are not eligible; must have received at least one line of therapy with evidence of cancer progression within 6 months after the last dose of platinum-based therapy (ie, having a platinum-free interval of <6 months [platinum resistant]), or progressive disease during or immediately after primary platinum-therapy, (ie, platinum refractory).
  • TNBC: Advanced or metastatic ER-negative, PR-negative, HER2-negative primary breast cancer previously treated and progressed on a taxane-based chemotherapy regimen; no previous or synchronous second breast cancer, unless also confirmed ER-, PR- and HER2-negative; must have received at least one line of therapy in the metastatic setting.
  • Other Solid Tumor: Other advanced or metastatic solid tumor previously treated with and progressed on a taxane-based chemotherapy regimen, with the exception of metastatic colorectal cancer, primary brain tumors, and neuroendocrine tumors that secrete ACTH or CRH; must have received no more than 4 prior lines of cytotoxic or myelosuppressive therapy Other Key Inclusion Criteria:
  • At least 18 years of age
  • ECOG performance status 0 or 1
  • Measurable disease as assessed centrally using RECIST 1.1
  • Treated, stable CNS metastases must be asymptomatic and must not require steroids
  • Agreement and ability to undergo two on-study biopsies, one pre-treatment obtained prior to dosing and during Cycle 2
  • 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)
  • Albumin ≥3.0 g/dL
  • 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
  • Ability to swallow ORIC-101 intact without chewing or crushing the capsules or tablets
  • Adequate gastrointestinal absorption. If the patient has undergone gastric bypass surgery and/or surgery of gastrointestinal or hepatobiliary tract, the patient must demonstrate adequate absorption as evidenced by albumin ≥3.0 g/dL, controlled pancreatic insufficiency (if present), and lack of evidence of malabsorption

Exclusion Criteria

  • Any other current or active malignancy
  • Prior or current treatment with ORIC-101 or any other GR antagonist (eg, mifepristone, relacorilant)
  • Concurrent treatment with any other anticancer therapy including chemotherapy, hormonal therapy, immunotherapy, radiotherapy, chemoembolization, targeted therapy, or an investigational agent within 28 days prior to Cycle 1 Day 1
  • Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or incomplete recovery from adverse effects resulting from such procedures; palliative radiotherapy within 1 week of Cycle 1 Day 1
  • Systemic, inhaled, or prescription strength topical corticosteroids within 21 days prior to Cycle 1 Day 1; short courses (≤5 days) for non-cancer-related reasons are allowed if clinically required
  • Grade 2 (moderate) or higher peripheral neuropathy per CTCAE v5.0; patients with mild peripheral neuropathy may be eligible at the discretion of the investigator in consultation with ORIC
  • All other toxicities from prior therapy (except alopecia) that have not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 ≤ Grade 1
  • Females: history of unexplained vaginal bleeding in the 8 weeks prior to Cycle 1 Day 1 (given potential for ORIC-101 to exacerbate such bleeding)
  • Females: use of hormone replacement therapy; hormone replacement therapy must be discontinued to allow for confirmation of postmenopausal status
  • History of Cushing's syndrome or adrenal insufficiency
  • Current (within 10 days prior to Cycle 1 Day 1) or expected on-study treatment with specified strong CYP3A4 inhibitors or inducers
  • Known human immunodeficiency virus (HIV) infection, unless patient is healthy and has a low risk of AIDS-related outcomes
  • Presence of Hepatitis B surface antigen (HBsAg) at screening
  • Positive Hepatitis C (HCVAb) antibody test result at screening or within 3 months prior to Cycle 1 Day 1. NOTE: Patients with positive HCVAb due to prior resolved disease can be enrolled if a confirmatory negative Hepatitis C RNA test is obtained
  • Positive Hepatitis C RNA test result at screening or within 3 months prior to Cycle 1 Day 1. NOTE: Test is optional and patients with negative HCVAb test are not required to also undergo Hepatitis C RNA testing

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: CLOSED_TO_ACCRUAL
San Francisco
UCSF Medical Center-Mount Zion
Status: ACTIVE
Contact: Helen Diller Family Comprehensive Cancer Center
Phone: 877-827-3222

Oregon

Portland
OHSU Knight Cancer Institute
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: APPROVED

ORIC-101 is a small molecule GR antagonist being developed for the treatment of patients with solid tumor malignancies. Mechanistically, ORIC-101 inhibits GR transcriptional activity and blocks the pro-survival signals mediated by the activated nuclear receptor. This is an open-label, uncontrolled, multicenter, dose-finding study to assess the safety and preliminary antitumor activity of ORIC-101 in combination with nab-paclitaxel or other anticancer therapy in patients with advanced or metastatic solid tumors. The study will begin with dose finding in combination initially with nab-paclitaxel in patients with various solid tumors (Part I); additional dose expansion cohorts in specific tumor types with nab-paclitaxel (Part II) or with other anticancer therapies may be evaluated through protocol amendment(s). The study will first evaluate intermittent administration (5 days on, 2 days off for 21 days) of ORIC-101 followed by continuous administration (daily for 21 days) in combination with nab-paclitaxel using a standard 3+3 dose escalation design. In Part II, patients will be enrolled across four cohorts of advanced or metastatic disease: - pancreatic ductal adenocarcinoma (PDAC) - ovarian cancer - triple negative breast cancer (TNBC) - other solid tumors

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Oric Pharmaceuticals

  • Primary ID 101-18101
  • Secondary IDs NCI-2019-04760
  • Clinicaltrials.gov ID NCT03928314