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

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: ORIC-114; Drug: Chemotherapy drug

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ORIC Clinical; Phone Number: 650-388-5600; Email: clinical@oricpharma.com

Study Locations

• Australia
  • Camperdown, Australia
    • Recruiting
    • Chris O'Brien Lifehouse
  • Melbourne, Australia
    • Not yet recruiting
    • Peter MacCallum Cancer Centre
  • Nedlands, Australia
    • Recruiting
    • One Clinical Research, Hollywood Medical Centre
  • Sydney, Australia
    • Recruiting
    • Sydney Adventist Health
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Not yet recruiting
      • Princess Margaret Cancer Centre
• Hong Kong
  • Shatin, Hong Kong
    • Not yet recruiting
    • The Chinese University of Hong Kong
• Korea, Republic of
  • Cheongju-si, Korea, Republic of
    • Recruiting
    • Chungbuk University Hospital
  • Goyang-si, Korea, Republic of
    • Recruiting
    • National Cancer Center
  • Gyeonggi-do, Korea, Republic of
    • Recruiting
    • Catholic University of Korea, St, Vincent Hospital
  • Incheon, Korea, Republic of
    • Recruiting
    • Gachon University Hospital
  • Seongnam-si, Korea, Republic of
    • Recruiting
    • Seoul National Bundang Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital, Yonsei University Health System
• Poland
  • Gdańsk, Poland
    • Not yet recruiting
    • Medical University of Gdańsk
• Taiwan
  • Taipei, Taiwan
    • Not yet recruiting
    • National Taiwan University Hospital
• United Kingdom
  • England
    • Manchester, England, United Kingdom
      • Not yet recruiting
      • The Christie NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
    • Huntington Beach, California, United States, 90813
      • Recruiting
      • City of Hope
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope
    • Long Beach, California, United States, 90813
      • Recruiting
      • City of Hope
    • San Francisco, California, United States, 94122
      • Recruiting
      • University of California, San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Not yet recruiting
      • Georgetown University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Not yet recruiting
      • Mayo Clinic
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10016
      • Not yet recruiting
      • NYU Langone Health Perlmutter Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Not yet recruiting
      • Duke Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • University of Pennsylvania
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Not yet recruiting
      • Spartanburg Regional Healthcare System
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / 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; Drug: Chemotherapy drug; 21 days for up to 4 cycles; Other Names: carboplatin and pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (RP2D)	RP2D as determined by interval 3+3 dose escalation design	12 months
Maximum plasma concentration (Cmax)	PK of ORIC-114	28 Days
Time of maximum observed concentration (Tmax)	PK of ORIC-114	28 Days
Area under the curve (AUC)	PK of ORIC-114	28 Days
Apparent plasma terminal elimination half-life (t1/2)	PK of ORIC-114	28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Duration of response (DOR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Clinical benefit rate (CBR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Progression-free survival (PFS)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Intracranial response rate (CR and/or PR)	Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Intracranial progression-free survival (PFS)	Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months

Collaborators and Investigators

• Sponsor: ORIC Pharmaceuticals
• Investigators: Study Director: Pratik S. Multani, MD, MS, ORIC Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: March 24, 2022
• First Submitted That Met QC Criteria: April 6, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Breast cancer; EGFR exon 20 insertion mutation; HER2 exon 20 insertion mutation; HER2 amplification/overexpression; Atypical EGFR mutation
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Pemetrexed
• Other Study ID Numbers: ORIC-114-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No