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
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
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