Clinical Trial 22441

• Overview

  Study Title:

  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

  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.

  Objective:

  PRIMARY OBJECTIVES: * Part I: To assess the safety and tolerability of ORIC-114 as a single agent * Part II: To select the optimal ORIC-114 RP2D for Phase 2 expansion cohorts * Part III (US only): To assess the safety and tolerability of ORIC-114 in combination with carboplatin- pemetrexed * Parts I, II, & III (US only): To assess the pharmacokinetics (PK) of ORIC-114 SECONDARY OBJECTIVES * Parts I & II: To evaluate the preliminary antitumor activity of ORIC-114 as a single agent * Part III (US only): To evaluate the preliminary antitumor activity of ORIC-114 in combination with carboplatin-pemetrexed * Parts I & II: To determine the preliminary intracranial activity of ORIC-114 in patients presenting with brain lesions at baseline * Part III (US only): To determine the preliminary intracranial activity of ORIC-114 in combination with carboplatin-pemetrexed in patients presenting with brain lesions at baseline EXPLORATORY OBJECTIVES * Parts I, II, & III (US only): To characterize and/or quantify metabolites of ORIC-114 in plasma * Parts I, II, & III (US only): To gain insight into molecular alterations which may confer tumor sensitivity to treatment with ORIC-114

• Treatments

  Therapies:

  Chemotherapy (NOS); Tyrosine Kinase Inhibitor

  Medications:

  Alimta (Pemetrexed); ORIC-114 (); Paraplatin (carboplatin); Pemetrexed (); carboplatin ()

• Inclusion Criteria

  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 Part I Extension:
  • 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 Part II Dose Optimization: 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function

• Exclusion Criteria

  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

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