Recruiting
Phase 1
Phase 2

ORIC-114

Sponsor:

ORIC Pharmaceuticals

Code:

NCT05315700

Conditions

Solid Tumors

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ORIC-114

Chemotherapy drug

Study Details

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), 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.

Conditions

Solid Tumors

Study ID

NCT05315700

Start date

Mar 10, 2022

Status verified date

Sep, 2026

Completion date

Sep, 2027

Anticipated

Primary completion date

Sep, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

350 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation and Dose Optimization

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

experimental: Combination Dose Escalation

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

Interventions

ORIC-114

ORIC-114 oral daily

Chemotherapy drug

21 days for up to 4 cycles

Primary outcome measure

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
  • Maximum plasma concentration (Cmax) [ Time Frame: 28 Days ]
  • Time of maximum observed concentration (Tmax) [ Time Frame: 28 Days ]
  • Area under the curve (AUC) [ Time Frame: 28 Days ]
  • Apparent plasma terminal elimination half-life (t1/2) [ Time Frame: 28 Days ]

Central Contacts and Locations

Central contacts

ORIC Clinical

650-388-5600clinical@oricpharma.com

Locations

City of Hope

Recruiting

Duarte, California, United States, 91010

City of Hope

Recruiting

Huntington Beach, California, United States, 90813

City of Hope

Recruiting

Irvine, California, United States, 92618

City of Hope

Recruiting

Long Beach, California, United States, 90813

University of California, San Francisco

Recruiting

San Francisco, California, United States, 94122

Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06510

Georgetown University

Recruiting

Washington D.C., District of Columbia, United States, 20007

Mayo Clinic

Recruiting

Jacksonville, Florida, United States, 32224

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

NYU Langone Health Perlmutter Cancer Center

Recruiting

New York, New York, United States, 10016

Duke Cancer Institute

Recruiting

Durham, North Carolina, United States, 27710

University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Spartanburg Regional Healthcare System

Recruiting

Spartanburg, South Carolina, United States, 29303

Next Oncology

Recruiting

Fairfax, Virginia, United States, 22031

Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G 2C4

More Information

Sponsor

ORIC Pharmaceuticals

Last update posted

Sep 4, 2026

Last verified

Sep, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by ORIC Pharmaceuticals on 2026-09-04.