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Trial record 1 of 1 for:    ORIC-114
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Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05315700
Recruitment Status : Recruiting
First Posted : April 7, 2022
Last Update Posted : May 3, 2023
Sponsor:
Information provided by (Responsible Party):
ORIC Pharmaceuticals

Brief Summary:
The purpose of this study is to establish the recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), preliminary antitumor ORIC-114 when administered to patients with advanced solid tumors harboring an EGFR or HER2 alteration.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: ORIC-114 Phase 1

Detailed Description:

ORIC-114 is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor of EGFR and HER2 alterations, including exon 20 insertion mutations.

This is a first-in-human, open-label, single arm, multicenter, dose escalation followed by dose expansion study to establish the recommended phase 2 dose (RP2D) and preliminary antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options

The study will begin with dose finding in patients with various solid tumors (Dose Escalation); additional dose expansion cohorts in specific tumor types (Dose Expansion), treatment history, and/or expression of a specific biomarker may be initiated via protocol amendment.

The study will evaluate escalating dose levels of ORIC-114 administered orally, daily in 28-day cycles following an accelerated titration design used for Dose Level 1, after which, escalating doses of ORIC-114 will be administered following an interval 3+3 design.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Interval 3+3 dose escalation design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1/1b, Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Actual Study Start Date : March 10, 2022
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2025

Arm Intervention/treatment
Experimental: Dose Escalation
ORIC-114 dosed orally on a continuous daily dosing regimen in 28-day cycles.
Drug: ORIC-114
ORIC-114 oral daily for 28 days




Primary Outcome Measures :
  1. Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
    RP2D as determined by interval 3+3 dose escalation design

  2. Maximum plasma concentration (Cmax) [ Time Frame: 28 Days ]
    PK of ORIC-114

  3. Time of maximum observed concentration (Tmax) [ Time Frame: 28 Days ]
    PK of ORIC-114

  4. Area under the curve (AUC) [ Time Frame: 28 Days ]
    PK of ORIC-114

  5. Apparent plasma terminal elimination half-life (t1/2) [ Time Frame: 28 Days ]
    PK of ORIC-114


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  2. Duration of response (DOR) [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  3. Clinical benefit rate (CBR) [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  4. Progression-free survival (PFS) [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  5. Intracranial response rate (CR and/or PR) [ Time Frame: 36 months ]
    Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  6. Intracranial progression-free survival (PFS) [ Time Frame: 36 months ]
    Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented EGFR or HER2 exon 20 insertion mutation as determined by any nucleic acid-based diagnostic testing method, or HER2 amplification/overexpression as determined by an immunohistochemistry (IHC) or an in situ hybridization (ISH) test
  • Previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable

    -- NSCLC patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum-based chemotherapy is contraindicated

  • Agreement and ability to undergo pretreatment biopsy
  • Measurable disease according to RECIST 1.1
  • CNS involvement which is either previously treated and controlled, or asymptomatic
  • ECOG performance status of 0 or 1
  • Adequate organ function

Exclusion Criteria:

  • Known EGFR T790M mutation
  • Leptomeningeal disease and spinal cord compression

    -- Except if LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator; the subject must be free of neurological symptoms of LMD

  • History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
  • Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
  • Known, symptomatic human immunodeficiency virus (HIV) infection
  • Known active infection requiring treatment or history of hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients positive for HBsAg but normal HBV DNA level are allowed.
  • Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes
  • Any other concurrent serious uncontrolled medical, psychological, or addictive conditions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05315700


Contacts
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Contact: ORIC Clinical 650-388-5600 clinical@oricpharma.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
ORIC Pharmaceuticals
Investigators
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Study Director: Pratik S. Multani, MD, MS ORIC Pharmaceuticals
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Responsible Party: ORIC Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05315700    
Other Study ID Numbers: ORIC-114-01
First Posted: April 7, 2022    Key Record Dates
Last Update Posted: May 3, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ORIC Pharmaceuticals:
EGFR exon 20 insertion mutation
HER2 exon 20 insertion mutation
HER2 amplification/overexpression
Additional relevant MeSH terms:
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Neoplasms