Study of ORIC-114 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.
Study details:
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).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- 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
- 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 criteria
- 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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT05315700
Intervention or treatment
DRUG: ORIC-114
DRUG: Chemotherapy drug
Conditions
- Solid Tumors
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Chris O'Brien Lifehouse
Select from list below to view details:
Chris O'Brien Lifehouse
Camperdown, Australia
Peter MacCallum Cancer Centre
Melbourne, Australia
One Clinical Research, Hollywood Medical Centre
Nedlands, Australia
Sydney Adventist Health
Sydney, Australia
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Who is running the clinical trial?
ORIC Pharmaceuticals
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Dose Escalation and Dose Optimization
| Drug: ORIC-114 |
EXPERIMENTAL: Combination Dose Escalation
| Drug: ORIC-114, Drug: Chemotherapy drug |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 36 months |
| Duration of response (DOR) | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 36 months |
| Clinical benefit rate (CBR) | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 36 months |
| Progression-free survival (PFS) | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 36 months |
| Intracranial response rate (CR and/or PR) | Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 36 months |
| Intracranial progression-free survival (PFS) | Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 36 months |
References
Clinical Trials Gov: Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 AlterationOther trials to consider
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