Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

September 1, 2026 updated by: ORIC Pharmaceuticals

An Open-Label, Phase 1/2 Study of ORIC-114 as a Single Agent or in Combination With Chemotherapy, in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

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), and antitumor activity of ORIC-114 as a Single Agent or in Combination with Chemotherapy when administered to patients with advanced solid tumors harboring an EGFR or HER2 alteration.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

ORIC-114 is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR and HER2 alterations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.

This is a first-in-human, open-label, single arm, multicenter, dose escalation study of ORIC-114 as a single agent (Part I), followed by dose optimization (Part II) to establish the recommended phase 2 dose (RP2D) and antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options. After the optimal RP2D has been determined, Phase 2 will be initiated via protocol amendment to add one or more expansion cohorts of patients with specific tumor types, treatment history, and/or expression of a specific biomarker to evaluate the antitumor activity of ORIC-114.

After completion of Part I dose escalation, Part III, a dose escalation study of ORIC-114 in combination with chemotherapy (carboplatin-pemetrexed) may be initiated to establish the RP2D and/or MTD and antitumor activity for the combination (US sites only).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
350

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
      • Camperdown, Australia
        • Recruiting
        • Chris O'Brien Lifehouse
      • Melbourne, Australia
        • Recruiting
        • Peter MacCallum Cancer Centre
      • Nedlands, Australia
        • Recruiting
        • One Clinical Research, Hollywood Medical Centre
      • Sydney, Australia
        • Recruiting
        • Sydney Adventist Health
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • Princess Margaret Cancer Centre
  • Hong Kong
      • Shatin, Hong Kong
        • Recruiting
        • The Chinese University of Hong Kong
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Recruiting
        • Hospital Kuala Lumpur
      • Kuala Lumpur, Malaysia
        • Recruiting
        • University of Malaya Medical Center (UMMC)
    • Pahang
      • Kuantan, Pahang, Malaysia
        • Recruiting
        • Sultan Ahmad Shah Medical Centre at International Islamic University Malaysia (IIUM)
    • Pulau Pinang
      • George Town, Pulau Pinang, Malaysia
        • Recruiting
        • Pulau Pinang Hospital
    • Sarawak
      • Kuching, Sarawak, Malaysia
        • Recruiting
        • Sarawak General Hospital (SGH)
  • Poland
      • Gdansk, Poland
        • Recruiting
        • Medical University of Gdańsk
  • South Korea
      • Cheongju-si, South Korea
        • Recruiting
        • Chungbuk University Hospital
      • Goyang-si, South Korea
        • Recruiting
        • National Cancer Center
      • Gyeonggi-do, South Korea
        • Recruiting
        • Catholic University of Korea, St, Vincent Hospital
      • Incheon, South Korea
        • Recruiting
        • Gachon University Hospital
      • Seongnam-si, South Korea
        • Recruiting
        • Seoul National Bundang Hospital
      • Seoul, South Korea
        • Recruiting
        • Samsung Medical Center
      • Seoul, South Korea
        • Recruiting
        • Asan Medical Center
      • Seoul, South Korea
        • Recruiting
        • Severance Hospital, Yonsei University Health System
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Vall d'Hebron Institute of Oncology (VHIO)
      • Barcelona, Spain
        • Recruiting
        • NEXT Oncology - Barcelona
      • Madrid, Spain
        • Recruiting
        • NEXT Oncology - Madrid
  • Taiwan
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital
  • United Kingdom
    • England
      • Manchester, England, United Kingdom
        • Recruiting
        • The Christie NHS Foundation Trust
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
      • Huntington Beach, California, United States, 90813
        • Recruiting
        • City of Hope
      • Irvine, California, United States, 92618
        • Recruiting
        • City of Hope
      • Long Beach, California, United States, 90813
        • Recruiting
        • City of Hope
      • San Francisco, California, United States, 94122
        • Recruiting
        • University of California, San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health Perlmutter Cancer Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
    • South Carolina
      • Spartanburg, South Carolina, United States, 29303
        • Recruiting
        • Spartanburg Regional Healthcare System
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • NEXT Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented EGFR or HER2 exon 20 insertion mutation or atypical EGFR 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

    1. Part I Dose Escalation (CLOSED) Any solid tumor with

      • EGFR exon 20 insertion mutation
      • HER2 exon 20 insertion mutation
      • Atypical EGFR mutations (NSCLC only) (Appendix 8)
      • HER2 amplification or overexpression (HER2+)
      • Previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable

    2. Part I Extension (ONGOING)

      • Cohort IA: Patients with HER2+ breast cancer previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
      • Cohort IB: NSCLC patients with EGFR exon 20 insertion mutation previously treated with chemotherapy and amivantamab
      • Cohort IC: Treatment-naïve NSCLC patients with EGFR exon 20 insertion mutation
      • Cohort ID: Treatment-naïve NSCLC patients with EGFR atypical mutations

    3. Part II Dose Optimization (ONGOING): NSCLC patients with

      • Cohort IIA: EGFR exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to an EGFR exon 20 targeted agent, ie, must have declined or be ineligible for all available exon 20 targeted therapies with proven benefit
      • Cohort IIB: HER2 exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to a HER2 exon 20 targeted TKI
      • Cohort IIC: Atypical EGFR mutation, patients may have received a prior EGFR TKI
  • Agreement and ability to undergo pretreatment biopsy
  • Measurable disease according to RECIST 1.1
  • CNS involvement, which is either previously treated and controlled, or untreated and 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Escalation and Dose Optimization
ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles.
Drug: ORIC-114
ORIC-114 oral daily
Experimental: Combination Dose Escalation
ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles.
Drug: ORIC-114
ORIC-114 oral daily
Drug: Chemotherapy drug
21 days for up to 4 cycles
Other Names:
  • carboplatin and pemetrexed

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Recommended Phase 2 Dose (RP2D)
Time Frame: 12 months
RP2D as determined by interval 3+3 dose escalation design
12 months
Maximum plasma concentration (Cmax)
Time Frame: 28 Days
PK of ORIC-114
28 Days
Time of maximum observed concentration (Tmax)
Time Frame: 28 Days
PK of ORIC-114
28 Days
Area under the curve (AUC)
Time Frame: 28 Days
PK of ORIC-114
28 Days
Apparent plasma terminal elimination half-life (t1/2)
Time Frame: 28 Days
PK of ORIC-114
28 Days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 36 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
36 months
Duration of response (DOR)
Time Frame: 36 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
36 months
Clinical benefit rate (CBR)
Time Frame: 36 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
36 months
Progression-free survival (PFS)
Time Frame: 36 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
36 months
Intracranial response rate (CR and/or PR)
Time Frame: 36 months
Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
36 months
Intracranial progression-free survival (PFS)
Time Frame: 36 months
Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ORIC Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Pratik S. Multani, MD, MS, ORIC Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 10, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 7, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ORIC-114-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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