Clinical Trials /

Study of ORIC-101 in Combination With Anticancer Therapy

NCT03928314

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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of ORIC-101 in Combination With Anticancer Therapy
  • Official Title: An Open-label Phase 1b Study of ORIC-101 in Combination With Anticancer Therapy in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 101-18101
  • NCT ID: NCT03928314

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
ORIC-101Dose Escalation
Nab-paclitaxelDose Escalation

Purpose

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

Detailed Description

      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 anticancer therapy in patients
      with advanced or metastatic solid tumors. The study will begin with dose finding in
      combination initially with nab-paclitaxel; additional dose-finding cohorts 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.

      Dose expansion may further evaluate the safety of ORIC-101 at a dose selected from dose
      escalation.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalORIC-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.
  • ORIC-101
  • Nab-paclitaxel
Dose ExpansionExperimentalRP2D dose
  • ORIC-101
  • Nab-paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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

          -  Positive Hepatitis C antibody test result at screening or within 3 months prior to
             starting study treatment

          -  Positive Hepatitis C RNA test result at screening or within 3 months prior to first
             dose of study treatment

          -  Unacceptable laboratory 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 (30 g/L)

               -  AST (SGOT) or ALT(SGPT) >2.5 × ULN

               -  AST (SGOT) or ALT (SGPT) >2.5 and ≤5.0 × ULN is acceptable for patients with
                  liver metastases

          -  Bilirubin >1.5 × ULN:

               -  Isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and
                  direct bilirubin <35% of total bilirubin

               -  Bilirubin >1.5 and ≤3.0 × ULN is acceptable for patients with known Gilbert's
                  disease

          -  QTcF >450 msec for males; QTcF >470 msec for females; or QTcF >480 msec for those with
             bundle branch block (BBB)

          -  Consumption of Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus
             fruits, grapefruit hybrids, or fruit juices containing these fruits from 10 days
             before the start of study treatment

          -  Sensitivity to any of the study treatments, or components thereof, or drug or other
             allergy that, in the opinion of the investigator, contraindicates participation in the
             study.

          -  Any other condition or circumstance (eg, 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D)
Time Frame:12 months
Safety Issue:
Description:RP2D as determined by 3+3 dose escalation design

Secondary Outcome Measures

Measure:Maximum plasma concentration (Cmax)
Time Frame:28 Days
Safety Issue:
Description:PK of ORIC-101 in combination with nab-paclitaxel
Measure:Time of maximum observed concentration (Tmax)
Time Frame:28 Days
Safety Issue:
Description:PK of ORIC-101 in combination with nab-paclitaxel
Measure:Area under the curve (AUC(0-t))
Time Frame:28 Days
Safety Issue:
Description:PK of ORIC-101 in combination with nab-paclitaxel
Measure:Number of Participants with Adverse Events
Time Frame:36 months
Safety Issue:
Description:Safety and tolerability of ORIC-101 in combination with nab-paclitaxel
Measure:Number of Participants with Abnormal Laboratory Values
Time Frame:36 months
Safety Issue:
Description:Safety and tolerability of ORIC-101 in combination with nab-paclitaxel
Measure:Number of Participants with Abnormal 12-lead ECG
Time Frame:36 months
Safety Issue:
Description:Safety and tolerability of ORIC-101 in combination with nab-paclitaxel
Measure:Number of Participants with Abnormal Vital Signs
Time Frame:36 months
Safety Issue:
Description:Safety and tolerability of ORIC-101 in combination with nab-paclitaxel
Measure:Number of Participants with Antitumor Activity
Time Frame:36 months
Safety Issue:
Description:Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oric Pharmaceuticals

Trial Keywords

  • GR antagonist
  • Glucocorticoid receptor antagonist

Last Updated

June 5, 2020