A Phase 1 interventional study of ORIC-114 Dose 1 + amivantamab and ORIC-114 Dose 2 + amivantamab in Solid Tumors, EGFR Exon 20 Insertion Mutations and NSCLC, sponsored by ORIC Pharmaceuticals. Recruiting at 4 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-24.
Sponsored by ORIC Pharmaceuticals · Phase 1, Interventional, and Treatment
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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.
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.
ORIC Pharmaceuticals is the lead sponsor of 10 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Prior Therapies:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ORIC-114 + amivantamab
Drug: ORIC-114 Dose 1 + amivantamab
ORIC-114 + amivantamab
Drug: ORIC-114 Dose 2 + amivantamab
ORIC-114 + amivantamab
Drug: ORIC-114 Dose 3 + amivantamab
Two potential ORIC-114 dose levels + amivantamab
Drug: ORIC-114 Dose 2 + amivantamab · Drug: ORIC-114 Dose 3 + amivantamab
Drug pages: Enozertinib · Amivantamab
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection
Drug pages: Enozertinib · Amivantamab
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection
Drug pages: Enozertinib · Amivantamab
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection
Recommended Phase 2 Dose (RP2D)
RP2D of ORIC-114 in combination with amivantamab by interval 3+3 dose escalation design
Time frame: 12 months
Objective response rate (ORR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: 12 months
Duration of response (DOR)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: 12 months
Progression-free survival (PFS)
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: 12 months
Plasma PK parameters
Peak Plasma Concentration (Cmax)
Time frame: 28 Days
Plasma PK parameters
Time of maximal plasma concentration (Tmax)
Time frame: 28 Days
Plasma PK parameters
Area under the plasma concentration vs time curve (AUC)
Time frame: 28 Days
Plasma PK parameters
Apparent plasma terminal elimination half-life (t1/2)
Time frame: 28 Days
BICR-Objective response rate (ORR)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Time frame: 12 months
BICR-Duration of response (DOR)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Time frame: 12 months
BICR-Progression-free survival (PFS)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Time frame: 12 months
Intracranial Objective response rate (ORR)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Time frame: 12 months
Intracranial Progression-free survival (PFS)
Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM
Time frame: 12 months
Plan to share: No
No publications or documents are linked to this record.
Started Feb 2025 (actual). Primary completion is estimated for Dec 2026, 22 months after the start.
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Studies of the drugs tested here: Enozertinib · Amivantamab
ORIC Pharmaceuticals