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

NCT ID: NCT05315700

Last Updated: 2025-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-10

Study Completion Date

2027-09-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Interval 3+3 dose escalation design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation and Dose Optimization

ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles.

Group Type EXPERIMENTAL

ORIC-114

Intervention Type DRUG

ORIC-114 oral daily

Combination Dose Escalation

ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles.

Group Type EXPERIMENTAL

ORIC-114

Intervention Type DRUG

ORIC-114 oral daily

Chemotherapy drug

Intervention Type DRUG

21 days for up to 4 cycles

Interventions

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ORIC-114

ORIC-114 oral daily

Intervention Type DRUG

Chemotherapy drug

21 days for up to 4 cycles

Intervention Type DRUG

Other Intervention Names

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carboplatin and pemetrexed

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ORIC Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pratik S. Multani, MD, MS

Role: STUDY_DIRECTOR

ORIC Pharmaceuticals

Locations

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City of Hope

Duarte, California, United States

Site Status RECRUITING

City of Hope

Huntington Beach, California, United States

Site Status RECRUITING

City of Hope

Irvine, California, United States

Site Status RECRUITING

City of Hope

Long Beach, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Yale Cancer Center

New Haven, Connecticut, United States

Site Status RECRUITING

Georgetown University

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Mayo Clinic

Jacksonville, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

NYU Langone Health Perlmutter Cancer Center

New York, New York, United States

Site Status RECRUITING

Duke Cancer Institute

Durham, North Carolina, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, United States

Site Status RECRUITING

Next Oncology

Fairfax, Virginia, United States

Site Status RECRUITING

Chris O'Brien Lifehouse

Camperdown, , Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status RECRUITING

One Clinical Research, Hollywood Medical Centre

Nedlands, , Australia

Site Status RECRUITING

Sydney Adventist Health

Sydney, , Australia

Site Status RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status RECRUITING

The Chinese University of Hong Kong

Shatin, , Hong Kong

Site Status RECRUITING

Sultan Ahmad Shah Medical Centre at International Islamic University Malaysia (IIUM)

Kuantan, Pahang, Malaysia

Site Status RECRUITING

Pulau Pinang Hospital

George Town, Pulau Pinang, Malaysia

Site Status RECRUITING

Sarawak General Hospital (SGH)

Kuching, Sarawak, Malaysia

Site Status RECRUITING

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Site Status RECRUITING

University of Malaya Medical Center (UMMC)

Kuala Lumpur, , Malaysia

Site Status RECRUITING

Medical University of Gdańsk

Gdansk, , Poland

Site Status RECRUITING

Chungbuk University Hospital

Cheongju-si, , South Korea

Site Status RECRUITING

National Cancer Center

Goyang-si, , South Korea

Site Status RECRUITING

Catholic University of Korea, St, Vincent Hospital

Gyeonggi-do, , South Korea

Site Status RECRUITING

Gachon University Hospital

Incheon, , South Korea

Site Status RECRUITING

Seoul National Bundang Hospital

Seongnam-si, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

NEXT Oncology - Barcelona

Barcelona, , Spain

Site Status RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Site Status RECRUITING

NEXT Oncology - Madrid

Madrid, , Spain

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

The Christie NHS Foundation Trust

Manchester, England, United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada Hong Kong Malaysia Poland South Korea Spain Taiwan United Kingdom

Central Contacts

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ORIC Clinical

Role: CONTACT

650-388-5600

Other Identifiers

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ORIC-114-01

Identifier Type: -

Identifier Source: org_study_id

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