Solid TumorsPhase 1/2NCT05315700
Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
A Phase 1/2 study testing ORIC-114 and Chemotherapy drug in people with Solid Tumors, run by ORIC Pharmaceuticals at 42 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- ORIC-114 and Chemotherapy drug
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 42 sitesin 10 countries
- Study dates
- 10 Mar 2022to Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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+)
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- 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
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
42 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
42 sites in 10 countries
United States17 sites, 17 recruiting
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
Northwestern University
Chicago, Illinois, 60611
- Recruiting
City of Hope
Duarte, California, 91010
- Recruiting
Duke Cancer Institute
Durham, North Carolina, 27710
- Recruiting
Next Oncology
Fairfax, Virginia, 22031
- Recruiting
City of Hope
Huntington Beach, California, 90813
- Recruiting
City of Hope
Irvine, California, 92618
- Recruiting
Mayo Clinic
Jacksonville, Florida, 32224
- Recruiting
City of Hope
Long Beach, California, 90813
- Recruiting
Yale Cancer Center
New Haven, Connecticut, 06510
- Recruiting
NYU Langone Health Perlmutter Cancer Center
New York, New York, 10016
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
- Recruiting
University of California, San Francisco
San Francisco, California, 94122
- Recruiting
Spartanburg Regional Healthcare System
Spartanburg, South Carolina, 29303
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
- Recruiting
Georgetown University
Washington D.C., District of Columbia, 20007
South Korea8 sites, 8 recruiting
- Recruiting
Chungbuk University Hospital
Cheongju-si
- Recruiting
National Cancer Center
Goyang-si
- Recruiting
Catholic University of Korea, St, Vincent Hospital
Gyeonggi-do
- Recruiting
Gachon University Hospital
Incheon
- Recruiting
Seoul National Bundang Hospital
Seongnam-si
- Recruiting
Asan Medical Center
Seoul
- Recruiting
Samsung Medical Center
Seoul
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul
Malaysia5 sites, 5 recruiting
- Recruiting
Pulau Pinang Hospital
George Town, Pulau Pinang
- Recruiting
Hospital Kuala Lumpur
Kuala Lumpur
- Recruiting
University of Malaya Medical Center (UMMC)
Kuala Lumpur
- Recruiting
Sultan Ahmad Shah Medical Centre at International Islamic University Malaysia (IIUM)
Kuantan, Pahang
- Recruiting
Sarawak General Hospital (SGH)
Kuching, Sarawak
Australia4 sites, 4 recruiting
- Recruiting
Chris O'Brien Lifehouse
Camperdown
- Recruiting
Peter MacCallum Cancer Centre
Melbourne
- Recruiting
One Clinical Research, Hollywood Medical Centre
Nedlands
- Recruiting
Sydney Adventist Health
Sydney
Spain3 sites, 3 recruiting
- Recruiting
NEXT Oncology - Barcelona
Barcelona
- Recruiting
Vall d'Hebron Institute of Oncology (VHIO)
Barcelona
- Recruiting
NEXT Oncology - Madrid
Madrid
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C4
Hong Kong1 site, 1 recruiting
- Recruiting
The Chinese University of Hong Kong
Shatin
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei
United Kingdom1 site, 1 recruiting
- Recruiting
The Christie NHS Foundation Trust
Manchester, England
About this study
Official 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
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.
Read the 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).
- Conditions
- Solid Tumors
- Being tested
- ORIC-114, Chemotherapy drug
- Keywords
- EGFR exon 20 insertion mutation, Atypical EGFR mutation, HER2 exon 20 insertion mutation, HER2 amplification/overexpression, NSCLC, Breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ORIC-114Drug
ORIC-114 oral daily
Chemotherapy drugDrug
Also called carboplatin and pemetrexed
21 days for up to 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and Dose Optimization | Experimental | ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles. Receives: Drug: ORIC-114 |
| Combination Dose Escalation | Experimental | ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles. Receives: Drug: ORIC-114; Drug: Chemotherapy drug |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase 2 Dose (RP2D)
RP2D as determined by interval 3+3 dose escalation design
Measured: 12 months
Maximum plasma concentration (Cmax)
PK of ORIC-114
Measured: 28 Days
Time of maximum observed concentration (Tmax)
PK of ORIC-114
Measured: 28 Days
Area under the curve (AUC)
PK of ORIC-114
Measured: 28 Days
Apparent plasma terminal elimination half-life (t1/2)
PK of ORIC-114
Measured: 28 Days
Secondary outcomes (6)
Objective response rate (ORR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Duration of response (DOR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Clinical benefit rate (CBR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Progression-free survival (PFS)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Intracranial response rate (CR and/or PR)
Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Intracranial progression-free survival (PFS)
Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2022
- Study start10 Mar 2022
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Interval 3+3 dose escalation design
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ORIC Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pratik S. Multani, MD, MS, Study director, ORIC Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05315700
- Sponsor's protocol ID
- ORIC-114-01
- Status last verified
- Nov 2026
- First submitted
- 24 Mar 2022
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT05315700
- Acronym / sponsor ID
- ORIC-114-01
- Conditions
- Solid Tumors
- Keywords
- EGFR exon 20 insertion mutation, Atypical EGFR mutation, HER2 exon 20 insertion mutation, HER2 amplification/overexpression, NSCLC, Breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- ORIC PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 10 Mar 2022 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 7 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Interval 3+3 dose escalation design
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Dose Optimization | Experimental | Drug: ORIC-114ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles. |
| Combination Dose Escalation | Experimental | Drug: ORIC-114, Drug: Chemotherapy drugORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ORIC-114ORIC-114 oral daily | Drug | Combination Dose Escalation, Dose Escalation and Dose Optimization |
| Chemotherapy drugAlso: carboplatin and pemetrexed21 days for up to 4 cycles | Drug | Combination Dose Escalation |
Primary outcome
Recommended Phase 2 Dose (RP2D)
Time frame: 12 months
RP2D as determined by interval 3+3 dose escalation design
Maximum plasma concentration (Cmax)
Time frame: 28 Days
PK of ORIC-114
Time of maximum observed concentration (Tmax)
Time frame: 28 Days
PK of ORIC-114
Area under the curve (AUC)
Time frame: 28 Days
PK of ORIC-114
Apparent plasma terminal elimination half-life (t1/2)
Time frame: 28 Days
PK of ORIC-114
6 secondary outcomes
Objective response rate (ORR)
Time frame: 36 months
Duration of response (DOR)
Time frame: 36 months
Clinical benefit rate (CBR)
Time frame: 36 months
Progression-free survival (PFS)
Time frame: 36 months
Intracranial response rate (CR and/or PR)
Time frame: 36 months
Intracranial progression-free survival (PFS)
Time frame: 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pratik S. Multani, MD, MS study director
ORIC Pharmaceuticals
42 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ORIC-114 and Chemotherapy drug in people with Solid Tumors, run by ORIC Pharmaceuticals at 42 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, South Korea, Malaysia, Australia, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ORIC Clinical (650-388-5600, clinical@oricpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended Phase 2 Dose (RP2D) (time frame: 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.