Share

Save

Study of ORIC-114 in Patients with Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

PHASE1PHASE2RECRUITING

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.

info
Simpliy with AI

Study details:

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 development in patients whose tumors harbor these alterations, including those with CNS metastases. This is a first-in-human, open-label, single arm, multicenter, dose escalation study of ORIC-114 as a single agent (Part I), followed by dose optimization (Part II) to establish the recommended phase 2 dose (RP2D) and antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options. After the optimal RP2D has been determined, Phase 2 will be initiated via protocol amendment to add one or more expansion cohorts of patients with specific tumor types, treatment history, and/or expression of a specific biomarker to evaluate the antitumor activity of ORIC-114.

After completion of Part I dose escalation, Part III, a dose escalation study of ORIC-114 in combination with chemotherapy (carboplatin-pemetrexed) may be initiated to establish the RP2D and/or MTD and antitumor activity for the combination (US sites only).

info
Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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 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
  • 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
  • info
    Simplify with AI

    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2022-03-10

    Primary completion: 2025-03-01

    Study completion finish: 2026-03-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

      PHASE2

    trial

    Trial ID

    NCT05315700

    Intervention or treatment

    DRUG: ORIC-114

    DRUG: Chemotherapy drug

    Conditions

    • Solid Tumors

    Find a site

    Closest Location:

    Peter MacCallum Cancer Centre

    Research sites nearby

    Select from list below to view details:

    • Peter MacCallum Cancer Centre

      Melbourne, Not Specified, Australia

    • Chris O'Brien Lifehouse

      Camperdown, Not Specified, Australia

    • One Clinical Research, Hollywood Medical Centre

      Nedlands, Not Specified, Australia

    • Sydney Adventist Health

      Sydney, Not Specified, Australia

    Loading...

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: Dose Escalation and Dose Optimization
    • ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles.
    DRUG: ORIC-114
    • ORIC-114 oral daily
    EXPERIMENTAL: Combination Dose Escalation
    • ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles.
    DRUG: ORIC-114
    • ORIC-114 oral daily

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Recommended Phase 2 Dose (RP2D)RP2D as determined by interval 3+3 dose escalation design12 months
    Maximum plasma concentration (Cmax)PK of ORIC-11428 Days
    Time of maximum observed concentration (Tmax)PK of ORIC-11428 Days
    Area under the curve (AUC)PK of ORIC-11428 Days
    Apparent plasma terminal elimination half-life (t1/2)PK of ORIC-11428 Days

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Objective response rate (ORR)Response Evaluation Criteria in Solid Tumors (RECIST) version 1.136 months
    Duration of response (DOR)Response Evaluation Criteria in Solid Tumors (RECIST) version 1.136 months
    Clinical benefit rate (CBR)Response Evaluation Criteria in Solid Tumors (RECIST) version 1.136 months
    Progression-free survival (PFS)Response Evaluation Criteria in Solid Tumors (RECIST) version 1.136 months
    Intracranial response rate (CR and/or PR)Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.136 months
    Intracranial progression-free survival (PFS)Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.136 months

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

    No questions submitted. Be the first to ask a question!

    You may be eligible to participate in this trial based on your search.Apply for study
    Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

    References

    Clinical Trials Gov: Study of ORIC-114 in Patients with Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

    Other trails to consider

    Top searched conditions