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ORIC-114 for Advanced Solid Tumors with EGFR or HER2 Alterations

This study is testing a new oral medicine called ORIC-114 for people with advanced solid tumors that have specific changes (mutations or amplifications) in the EGFR or HER2 genes. ORIC-114 is designed to target these changes, including in tumors that have spread to the brain. Researchers want to find the best dose of ORIC-114, understand its safety, and see how well it works alone or in combination with chemotherapy. You may be able to join if you are 18 or older, have a locally advanced or metastatic solid tumor, and have specific EGFR or HER2 alterations. The study aims to determine the recommended dose and how the body handles the drug within the first month, and to assess its overall safety and effectiveness over 12 months.

Study design
This is a first-in-human, open-label, single-arm study, meaning all participants will receive ORIC-114 and everyone involved will know what treatment is being given. The study plans to enroll 350 participants.
What's involved
Participants will take ORIC-114 daily by mouth. Some participants may also receive a chemotherapy drug for up to 4 cycles, with each cycle lasting 21 days.
Compensation
Not stated in the trial record.
Follow-up
Researchers will measure drug levels in your blood for 28 days and assess the recommended dose over 12 months.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05315700

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

Recruiting
PHASE1Ages 18+InterventionalTreatment
ORIC Pharmaceuticals
~350 participants
Updated 2025-08-05 on ClinicalTrials.gov
What's tested:ORIC-114Chemotherapy drug

At a glance

Recruiting sites
42 of 42 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Recommended Phase 2 Dose (RP2D)
Measured over 12 months
+4 more outcomes measured

Conditions

Solid Tumors

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Where it's being run

42 sites across 24 states
South Korea8
California5
Australia4
Spain3
Florida2
Malaysia2
Connecticut1
District of Columbia1

Study leadership

  • Pratik S. Multani, MD, MS · STUDY_DIRECTOR · ORIC Pharmaceuticals

Who to contact

ORIC Clinical
[email protected]
650-388-5600
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

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

Known EGFR T790M mutation
Leptomeningeal disease and spinal cord compression
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

What this trial measures

  • Recommended Phase 2 Dose (RP2D)12 months

    RP2D as determined by interval 3+3 dose escalation design

  • Maximum plasma concentration (Cmax)28 Days

    PK of ORIC-114

  • Time of maximum observed concentration (Tmax)28 Days

    PK of ORIC-114

  • Area under the curve (AUC)28 Days

    PK of ORIC-114

  • Apparent plasma terminal elimination half-life (t1/2)28 Days

    PK of ORIC-114