RecruitingPhase 1Phase 2NCT05315700
Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
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
Sponsor
ORIC Pharmaceuticals
Enrollment
350 participants
Start Date
Mar 10, 2022
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 18 Years
Inclusion Criteria21
- 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 Criteria9
- 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
Interventions
DRUGORIC-114
ORIC-114 oral daily
DRUGChemotherapy drug
21 days for up to 4 cycles
Locations(42)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05315700
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