Status:
RECRUITING
Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Lead Sponsor:
ORIC Pharmaceuticals
Conditions:
Solid Tumors
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
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-...
Detailed Description
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 devel...
Eligibility Criteria
Inclusion
- 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
- 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
- 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
- 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
- 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
Key Trial Info
Start Date :
March 10 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2027
Estimated Enrollment :
350 Patients enrolled
Trial Details
Trial ID
NCT05315700
Start Date
March 10 2022
End Date
September 1 2027
Last Update
August 5 2025
Active Locations (42)
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1
City of Hope
Duarte, California, United States, 91010
2
City of Hope
Huntington Beach, California, United States, 90813
3
City of Hope
Irvine, California, United States, 92618
4
City of Hope
Long Beach, California, United States, 90813