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

NCT05315700 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ORIC-114-01
• Study Type: interventional
• Target: 350
• Locations: 10 countries
• Sites: 42

Brief 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.

Conditions

Solid Tumors

Keywords

EGFR exon 20 insertion mutation; Atypical EGFR mutation; HER2 exon 20 insertion mutation; HER2 amplification/overexpression; NSCLC; Breast cancer

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Objective response rate (ORR)

  36 months

• Duration of response (DOR)

  36 months

• Clinical benefit rate (CBR)

  36 months

• Progression-free survival (PFS)

  36 months

• Intracranial response rate (CR and/or PR)

  36 months

Study Arms (2)

Dose Escalation and Dose Optimization

EXPERIMENTAL

ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles.

Drug: ORIC-114

Combination Dose Escalation

EXPERIMENTAL

ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles.

Drug: ORIC-114; Drug: Chemotherapy drug

Interventions

ORIC-114 DRUG

ORIC-114 oral daily

Combination Dose Escalation; Dose Escalation and Dose Optimization

Chemotherapy drug DRUG

21 days for up to 4 cycles

Also known as: carboplatin and pemetrexed

Combination Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Cohort ID: Treatment-naïve NSCLC patients with EGFR atypical mutations
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ORIC Pharmaceuticals: lead

Study Sites (42)

City of Hope

Duarte, California, 91010, United States

RECRUITING

City of Hope

Huntington Beach, California, 90813, United States

RECRUITING

City of Hope

Irvine, California, 92618, United States

RECRUITING

City of Hope

Long Beach, California, 90813, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94122, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06510, United States

RECRUITING

Georgetown University

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

NYU Langone Health Perlmutter Cancer Center

New York, New York, 10016, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27710, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, 29303, United States

RECRUITING

Next Oncology

Fairfax, Virginia, 22031, United States

RECRUITING

Chris O'Brien Lifehouse

Camperdown, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Australia

RECRUITING

One Clinical Research, Hollywood Medical Centre

Nedlands, Australia

RECRUITING

Sydney Adventist Health

Sydney, Australia

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

The Chinese University of Hong Kong

Shatin, Hong Kong

RECRUITING

Sultan Ahmad Shah Medical Centre at International Islamic University Malaysia (IIUM)

Kuantan, Pahang, Malaysia

RECRUITING

Pulau Pinang Hospital

George Town, Pulau Pinang, Malaysia

RECRUITING

Sarawak General Hospital (SGH)

Kuching, Sarawak, Malaysia

RECRUITING

Hospital Kuala Lumpur

Kuala Lumpur, Malaysia

RECRUITING

University of Malaya Medical Center (UMMC)

Kuala Lumpur, Malaysia

RECRUITING

Medical University of Gdańsk

Gdansk, Poland

RECRUITING

Chungbuk University Hospital

Cheongju-si, South Korea

RECRUITING

National Cancer Center

Goyang-si, South Korea

RECRUITING

Catholic University of Korea, St, Vincent Hospital

Gyeonggi-do, South Korea

RECRUITING

Gachon University Hospital

Incheon, South Korea

RECRUITING

Seoul National Bundang Hospital

Seongnam-si, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, South Korea

RECRUITING

NEXT Oncology - Barcelona

Barcelona, Spain

RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, Spain

RECRUITING

NEXT Oncology - Madrid

Madrid, Spain

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

The Christie NHS Foundation Trust

Manchester, England, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Pratik S. Multani, MD, MS

  ORIC Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

ORIC Clinical

CONTACT

650-388-5600; clinical@oricpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interval 3+3 dose escalation design

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: April 7, 2022
• Study Start: March 10, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (17); MY (5); KR (8); GB (1); CA (1); PL (1); TW (1); AU (4); HK (1); ES (3)