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Treatment with ORIC-114 for advanced solid tumors with EGFR or HER2 alterations

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

PHASE1; PHASE2 · ORIC Pharmaceuticals · NCT05315700

This study is testing a new drug called ORIC-114 to see if it can help people with advanced solid tumors that have specific genetic changes related to EGFR or HER2.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment350 (estimated)
Ages18 Years and up
SexAll
SponsorORIC Pharmaceuticals (industry)
Drugs / interventionsamivantamab, chemotherapy, radiation
Locations42 sites (Duarte, California and 41 other locations)
Trial IDNCT05315700 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates ORIC-114, a selective small molecule inhibitor targeting EGFR and HER2 alterations in patients with advanced solid tumors. The study is divided into three parts: an initial dose escalation to determine the recommended Phase 2 dose (RP2D) and maximum tolerated dose (MTD), followed by an expansion phase to assess the drug's antitumor activity in specific patient cohorts. The trial includes both monotherapy and a combination with chemotherapy for further evaluation of efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates are patients with advanced solid tumors harboring EGFR or HER2 alterations who have exhausted standard treatment options.

Not a fit: Patients without documented EGFR or HER2 alterations or those who have not progressed on standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have specific genetic alterations.

How similar studies have performed: Other studies targeting EGFR and HER2 alterations have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Duarte, California and 41 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

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

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.