Solid TumorsPhase 1NCT06816992
ORIC-114 in Combination With Subcutaneous Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC
A Phase 1 study testing ORIC-114 Dose 1 + amivantamab, ORIC-114 Dose 2 + amivantamab and ORIC-114 Dose 3 + amivantamab in people with Solid Tumors and EGFR Exon 20 Insertion Mutations, run by ORIC Pharmaceuticals at 4 sites in 3 countries.
Trial summary
The purpose of this study is to establish the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with advanced or metastatic NSCLC harboring an EGFR exon 20 insertion… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, EGFR Exon 20 Insertion Mutations, NSCLC
- What is being tested?
- ORIC-114 Dose 1 + amivantamab, ORIC-114 Dose 2 + amivantamab and ORIC-114 Dose 3 + amivantamab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 27 Feb 2025to Dec 2027
- Phase
- Phase 1
- 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 metastatic NSCLC with a documented EGFR exon 20 insertion mutation as determined locally by any nucleic acid-based diagnostic testing method; all tests should be performed in a CLIA certified or equivalently accredited laboratory
- Prior Therapies:
- Dose Escalation: Patients may have previously received and progressed on or after platinum-based chemotherapy or may be treatment naïve
- Dose Expansion: Patients must not have received any prior therapy; at time of enrollment, patients must decline, or be ineligible for all available standard of care therapies with proven benefit
- Agreement and ability to undergo a pretreatment biopsy, provided the procedure is clinically feasible and not deemed unsafe by the investigator
- Measurable disease according to RECIST 1.1
Show all 9Show fewer
- Patients with asymptomatic CNS metastases are eligible
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
Who cannot join
- Known small cell lung cancer transformation
- Leptomeningeal disease
- Spinal cord compression not definitively treated with surgery or radiation
- Prior immunotherapy
- Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
- Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact absorption of ORIC-114
Trial locations and contacts
4 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 3 countries
United States2 sites, 2 recruiting
- Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
- Recruiting
NYU Langone Health
New York, New York, 10016
Australia1 site, 1 recruiting
- Not yet recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 03000
Canada1 site, 1 recruiting
- Not yet recruiting
The Princess Margaret Hospital
Toronto, Ontario, M5G 1Z5
About this study
Official title: Phase 1b Study of ORIC-114 in Combination With Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC
The purpose of this study is to establish the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutation.
Read the detailed description
ORIC-114, is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR exon 20 insertion mutations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.
Amivantamab is a bispecific EGFR-directed and MET receptor-directed antibody indicated in combination with carboplatin and pemetrexed for the first line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations and also as a single agent in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
This is an open-label, single arm, multicenter, dose escalation followed by dose expansion study to assess the safety and preliminary antitumor activity of ORIC-114 in combination with SC amivantamab, in patients with locally advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutations.
- Being tested
- ORIC-114 Dose 1 + amivantamab, ORIC-114 Dose 2 + amivantamab, ORIC-114 Dose 3 + amivantamab
- Keywords
- NSCLC, EGFR mutations, EGFR exon20, EGFR exon 20 insertion mutations, ORIC-114, Amivantamab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ORIC-114 Dose 1 + amivantamabDrug
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection
ORIC-114 Dose 2 + amivantamabDrug
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection
ORIC-114 Dose 3 + amivantamabDrug
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Dose Escalation level 1 | Experimental | ORIC-114 + amivantamab Receives: Drug: ORIC-114 Dose 1 + amivantamab |
| Part 1 Dose Escalation level 2 | Experimental | ORIC-114 + amivantamab Receives: Drug: ORIC-114 Dose 2 + amivantamab |
| Part 1 Dose Escalation level 3 | Experimental | ORIC-114 + amivantamab Receives: Drug: ORIC-114 Dose 3 + amivantamab |
| Part 2 Dose Expansion | Experimental | Two potential ORIC-114 dose levels + amivantamab Receives: Drug: ORIC-114 Dose 2 + amivantamab; Drug: ORIC-114 Dose 3 + amivantamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase 2 Dose (RP2D)
RP2D of ORIC-114 in combination with amivantamab by interval 3+3 dose escalation design
Measured: 12 months
Objective response rate (ORR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 12 months
Duration of response (DOR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 12 months
Progression-free survival (PFS)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 12 months
Secondary outcomes (9)
Plasma PK parameters
Peak Plasma Concentration (Cmax)
Measured: 28 Days
Plasma PK parameters
Time of maximal plasma concentration (Tmax)
Measured: 28 Days
Plasma PK parameters
Area under the plasma concentration vs time curve (AUC)
Measured: 28 Days
Plasma PK parameters
Apparent plasma terminal elimination half-life (t1/2)
Measured: 28 Days
BICR-Objective response rate (ORR)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Measured: 12 months
BICR-Duration of response (DOR)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Measured: 12 months
BICR-Progression-free survival (PFS)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Measured: 12 months
Intracranial Objective response rate (ORR)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Measured: 12 months
Intracranial Progression-free survival (PFS)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2025
- Study start27 Feb 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Interval 3+3 dose escalation design followed by dose expansion
- Masking
- None (open label)
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ORIC Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Responsible party
- Sponsor
- Investigators
- Pratik S. Multani, MD, MS, Study director, ORIC Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06816992
- Sponsor's protocol ID
- ORIC-114-05
- Status last verified
- Apr 2026
- First submitted
- 3 Feb 2025
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b Study of ORIC-114 in Combination With Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC
- ClinicalTrials.gov ID
- NCT06816992
- Acronym / sponsor ID
- ORIC-114-05
- Keywords
- NSCLC, EGFR mutations, EGFR exon20, EGFR exon 20 insertion mutations, ORIC-114, Amivantamab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- ORIC PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Study start
- 27 Feb 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Feb 2025 (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), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutation.
Detailed description
ORIC-114, is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR exon 20 insertion mutations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.
Amivantamab is a bispecific EGFR-directed and MET receptor-directed antibody indicated in combination with carboplatin and pemetrexed for the first line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations and also as a single agent in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
This is an open-label, single arm, multicenter, dose escalation followed by dose expansion study to assess the safety and preliminary antitumor activity of ORIC-114 in combination with SC amivantamab, in patients with locally advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Interval 3+3 dose escalation design followed by dose expansion
| Arm | Type | Receives |
|---|---|---|
| Part 1 Dose Escalation level 1 | Experimental | Drug: ORIC-114 Dose 1 + amivantamabORIC-114 + amivantamab |
| Part 1 Dose Escalation level 2 | Experimental | Drug: ORIC-114 Dose 2 + amivantamabORIC-114 + amivantamab |
| Part 1 Dose Escalation level 3 | Experimental | Drug: ORIC-114 Dose 3 + amivantamabORIC-114 + amivantamab |
| Part 2 Dose Expansion | Experimental | Drug: ORIC-114 Dose 2 + amivantamab, Drug: ORIC-114 Dose 3 + amivantamabTwo potential ORIC-114 dose levels + amivantamab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically confirmed metastatic NSCLC with a documented EGFR exon 20 insertion mutation as determined locally by any nucleic acid-based diagnostic testing method; all tests should be performed in a CLIA certified or equivalently accredited laboratory
- Prior Therapies:
- Agreement and ability to undergo a pretreatment biopsy, provided the procedure is clinically feasible and not deemed unsafe by the investigator
- Measurable disease according to RECIST 1.1
- Patients with asymptomatic CNS metastases are eligible
Key exclusion criteria (6 listed)
- Known small cell lung cancer transformation
- Leptomeningeal disease
- Spinal cord compression not definitively treated with surgery or radiation
- Prior immunotherapy
- 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-114 Dose 1 + amivantamabORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection | Drug | Part 1 Dose Escalation level 1 |
| ORIC-114 Dose 2 + amivantamabORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection | Drug | Part 1 Dose Escalation level 2, Part 2 Dose Expansion |
| ORIC-114 Dose 3 + amivantamabORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection | Drug | Part 1 Dose Escalation level 3, Part 2 Dose Expansion |
Primary outcome
Recommended Phase 2 Dose (RP2D)
Time frame: 12 months
RP2D of ORIC-114 in combination with amivantamab by interval 3+3 dose escalation design
Objective response rate (ORR)
Time frame: 12 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Duration of response (DOR)
Time frame: 12 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Progression-free survival (PFS)
Time frame: 12 months
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
9 secondary outcomes
Plasma PK parameters
Time frame: 28 Days
Plasma PK parameters
Time frame: 28 Days
Plasma PK parameters
Time frame: 28 Days
Plasma PK parameters
Time frame: 28 Days
BICR-Objective response rate (ORR)
Time frame: 12 months
BICR-Duration of response (DOR)
Time frame: 12 months
BICR-Progression-free survival (PFS)
Time frame: 12 months
Intracranial Objective response rate (ORR)
Time frame: 12 months
Intracranial Progression-free survival (PFS)
Time frame: 12 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 24 Apr 2026.
- Individual participant dataSharing planned: No
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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
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ORIC-114 Dose 1 + amivantamab, ORIC-114 Dose 2 + amivantamab and ORIC-114 Dose 3 + amivantamab in people with Solid Tumors and EGFR Exon 20 Insertion Mutations, run by ORIC Pharmaceuticals at 4 sites in 3 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 9 inclusion and 6 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 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Australia, Canada. 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 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.
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 4 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 24 Apr 2026.