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
Trial Description
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 Requirements
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
- Previously received and progressed on or after available standard therapies and for
whom additional standard therapy is considered unsuitable or intolerable
- In Parts I and II NSCLC patients must have received platinum-based chemotherapy
or other chemotherapy regimen if platinum-based chemotherapy is contraindicated
- Part II Dose Optimization Cohort IIA: patients must either be naïve to an EGFR
exon 20 targeted agent or only have received prior amivantamab, Cohort IIB:
patients must be naïve to a HER2 targeted TKI, Cohort IIC: patients may have
received a prior EGFR TKI
- In Part III, patients may have received any number of prior treatments
- 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