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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• City of Hope
  Duarte, California, United States Recruiting
• City of Hope
  Huntington Beach, California, United States Recruiting
• City of Hope
  Irvine, California, United States Recruiting
• City of Hope
  Long Beach, California, United States Recruiting
• University of California, San Francisco
  San Francisco, California, United States Recruiting
• Yale Cancer Center
  New Haven, Connecticut, United States Recruiting

Study contacts

• Study coordinator: ORIC Clinical
• Email: clinical@oricpharma.com
• Phone: 650-388-5600

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.