RECRUITING

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

Conditions

Solid Tumors EGFR exon 20 insertion mutation Atypical EGFR mutation HER2 exon 20 insertion mutation HER2 amplification/overexpression NSCLC Breast cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-03-10

Study Completion:2026-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05315700

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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	* Known EGFR T790M mutation * Leptomeningeal disease and spinal cord compression * 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

Inclusion Criteria

Exclusion 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
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

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

Contacts and Locations

Study Contact

ORIC Clinical

CONTACT

650-388-5600

clinical@oricpharma.com

Principal Investigator

Pratik S. Multani, MD, MS

STUDY_DIRECTOR

ORIC Pharmaceuticals

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

City of Hope

Huntington Beach, California, 90813

United States

City of Hope

Irvine, California, 92618

United States

City of Hope

Long Beach, California, 90813

United States

University of California, San Francisco

San Francisco, California, 94122

United States

Yale Cancer Center

New Haven, Connecticut, 06510

United States

Georgetown University

Washington, District of Columbia, 20007

United States

Mayo Clinic

Jacksonville, Florida, 32224

United States

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Northwestern University

Chicago, Illinois, 60611

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Mayo Clinic

Rochester, Minnesota, 55905

United States

NYU Langone Health Perlmutter Cancer Center

New York, New York, 10016

United States

Duke Cancer Institute

Durham, North Carolina, 27710

United States

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, 29303

United States

Next Oncology

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: ORIC Pharmaceuticals

Pratik S. Multani, MD, MS, STUDY_DIRECTOR, 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 Registration Dates

Study Start Date2022-03-10

Study Completion Date2026-03

Study Record Updates

Study Start Date2022-03-10

Study Completion Date2026-03

Terms related to this study

Keywords Provided by Researchers

EGFR exon 20 insertion mutation
Atypical EGFR mutation
HER2 exon 20 insertion mutation
HER2 amplification/overexpression
NSCLC
Breast cancer

Additional Relevant MeSH Terms

Solid Tumors