Study of ORIC-114 in Patients with Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
- Registration Number
- 2024-512264-66-00
- Lead Sponsor
- ORIC Pharmaceuticals Inc.
- Brief Summary
Part I: To assess the safety and tolerability of ORIC-114 as a single agent
Part II: To select the optimal ORIC-114 RP2D for Phase 2 expansion cohorts
Part III: To assess the safety and tolerability of ORIC-114 in combination with carboplatin-pemetrexed
Parts I, II, & III: To assess the pharmacokinetics (PK) of ORIC-114
- 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).
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 30
Aged ≥18 years at the time of signing the informed consent
Able to swallow oral medication without chewing or crushing.
Women of childbearing potential must have a negative serum pregnancy test within 72 hours before starting study treatment.
Women of childbearing potential and men who are not surgically sterile must agree to use highly effective medically accepted method of birth control during the study and for 90 days after end of treatment.
Willing and able to give informed consent and comply with protocol requirements for the duration of the study.
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 described in the protocol.
Prior Therapies as described in the protocol.
Agreement and ability to undergo pretreatment biopsy, provided the procedure is clinically feasible and not deemed unsafe by the investigator
Measurable disease according to RECIST 1.1
Patients with CNS involvement, which is either previously treated and controlled or untreated and asymptomatic are eligible.
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study drug are eligible.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate organ function as defined by the criteria included in the protocol.
Patients with known EGFR T790M mutation.
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. Testing is not required in the absence of history.
Active gastrointestinal disease (eg, Crohn’s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption.
Any other concurrent serious uncontrolled medical, psychological, or addictive conditions that, in the opinion of the investigator, may interfere with protocol compliance or contraindicates participation in the study.
Current participation in another clinical study of an investigational agent, vaccine, or device; concomitant participation in observational studies is acceptable after sponsor approval.
Leptomeningeal disease (LMD) and spinal cord compression.
Treated with any other anticancer therapy or herbal (alternative) medicines within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug.
Radiotherapy within 2 weeks prior to first dose of study drug (palliative radiation or stereotactic radiosurgery within 7 days prior to first dose of study drug); patients must have recovered from all radiotherapy-related toxicities.
Major surgery within 21 days prior to first dose of study drug or incomplete recovery from adverse effects resulting from such procedure.
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 of first dose of study.
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 human immunodeficiency virus (HIV) infection, unless patient is healthy and has a low risk of AIDS-related outcomes.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination Dose Escalation Chemotherapy drug ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles. Combination Dose Escalation ORIC-114 ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles. Dose Escalation and Dose Optimization ORIC-114 ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles.
- Primary Outcome Measures
Name Time Method Part I: Provisional RP2Ds and/or MTD of ORIC-114. Part I: Provisional RP2Ds and/or MTD of ORIC-114.
Part II: Optimal ORIC-114 RP2D. Part II: Optimal ORIC-114 RP2D.
Part III: RP2D and/or MTD of ORIC-114 in combination with carboplatin-pemetrexed Part III: RP2D and/or MTD of ORIC-114 in combination with carboplatin-pemetrexed
Incidence of adverse events, vital signs, evaluation of clinical laboratory results, 12-lead electrocardiogram (ECG), and other clinical assessments. Incidence of adverse events, vital signs, evaluation of clinical laboratory results, 12-lead electrocardiogram (ECG), and other clinical assessments.
PK profile as measured by Tmax, Cmax, Clast, AUClast, AUCtau, AUCinf, Kel, t1/2, CL/F, Vz/F, Rac(Cmax), and Rac(AUC) as appropriate PK profile as measured by Tmax, Cmax, Clast, AUClast, AUCtau, AUCinf, Kel, t1/2, CL/F, Vz/F, Rac(Cmax), and Rac(AUC) as appropriate
- Secondary Outcome Measures
Name Time Method Assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 • Objective response rate (ORR) (complete response [CR] or partial response [PR]), measured as changes in target and non-target lesions relative to baseline every 8 weeks • Duration of response (DOR), defined as time of first response to first documentation of radiographic progression or death, whichever occurs first. Assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 • Objective response rate (ORR) (complete response [CR] or partial response [PR]), measured as changes in target and non-target lesions relative to baseline every 8 weeks • Duration of response (DOR), defined as time of first response to first documentation of radiographic progression or death, whichever occurs first.
• Clinical benefit rate (CBR) (CR, PR, or stable disease [SD] ≥6 months) • Progression-free survival (PFS), defined as time from first dose of ORIC-114 to first documentation of radiographic progression or death, whichever occurs first • Clinical benefit rate (CBR) (CR, PR, or stable disease [SD] ≥6 months) • Progression-free survival (PFS), defined as time from first dose of ORIC-114 to first documentation of radiographic progression or death, whichever occurs first
Intracranial response will be assessed according to modified RECIST 1.1 and/or RANO-BM • Intracranial response rate (CR or PR) measured as changes in target and non-target CNS lesions • Intracranial PFS, defined as time from first dose of ORIC-114 to first documentation of radiographic progression in the brain or death, whichever occurs first. Intracranial response will be assessed according to modified RECIST 1.1 and/or RANO-BM • Intracranial response rate (CR or PR) measured as changes in target and non-target CNS lesions • Intracranial PFS, defined as time from first dose of ORIC-114 to first documentation of radiographic progression in the brain or death, whichever occurs first.
Trial Locations
- Locations (4)
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Pozuelo De Alarcon, Spain
Hospital Universitari Vall D Hebron
🇪🇸Barcelona, Spain
Uniwersyteckie Centrum Kliniczne🇵🇱Gdansk, PolandRafał DziadziuszkoSite contact+48585844471rafald@gumed.edu.pl