Ph 1/2 Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
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| ClinicalTrials.gov Identifier: NCT05315700 |
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Recruitment Status :
Recruiting
First Posted : April 7, 2022
Last Update Posted : December 8, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumors | Drug: ORIC-114 Drug: Chemotherapy drug | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 280 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | Interval 3+3 dose escalation design |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 10, 2022 |
| Estimated Primary Completion Date : | March 2025 |
| Estimated Study Completion Date : | March 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation and Dose Optimization
ORIC-114 dosed orally on a continuous daily dosing regimen in 28-day cycles.
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Drug: ORIC-114
ORIC-114 oral daily |
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Experimental: Combination Dose Escalation
ORIC-114 dosed orally on a continuous dosing regimen in 21-day cycles.
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Drug: ORIC-114
ORIC-114 oral daily Drug: Chemotherapy drug 21 days for up to 4 cycles
Other Name: carboplatin and pemetrexed |
- 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
- Objective response rate (ORR) [ Time Frame: 36 months ]Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Duration of response (DOR) [ Time Frame: 36 months ]Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Clinical benefit rate (CBR) [ Time Frame: 36 months ]Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Progression-free survival (PFS) [ Time Frame: 36 months ]Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Intracranial response rate (CR and/or PR) [ Time Frame: 36 months ]Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Intracranial progression-free survival (PFS) [ Time Frame: 36 months ]Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
- In Parts I and II NSCLC patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum-based chemotherapy is contraindicated
- Part II Dose Optimization Cohort IIA: patients must either be naïve to an EGFR exon 20 targeted agent or only have received prior amivantamab, Cohort IIB: patients must be naïve to a HER2 targeted TKI, Cohort IIC: patients may have received a prior EGFR TKI
- In Part III, patients may have received any number of prior treatments
- 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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05315700
| Contact: ORIC Clinical | 650-388-5600 | clinical@oricpharma.com |
Show 26 study locations
| Study Director: | Pratik S. Multani, MD, MS | ORIC Pharmaceuticals |
| Responsible Party: | ORIC Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT05315700 |
| Other Study ID Numbers: |
ORIC-114-01 |
| First Posted: | April 7, 2022 Key Record Dates |
| Last Update Posted: | December 8, 2023 |
| Last Verified: | December 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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EGFR exon 20 insertion mutation Atypical EGFR mutation HER2 exon 20 insertion mutation HER2 amplification/overexpression NSCLC |
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Neoplasms Carboplatin Pemetrexed Antineoplastic Agents |
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