A Phase I, Open-Label, Multi-Center Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of FGFR Inhibitor ET0111 Monotherapy in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- ET0111
- Conditions
- Advanced Solid Tumor
- Sponsor
- Etern BioPharma (Shanghai) Co., Ltd
- Enrollment
- 37
- Locations
- 5
- Primary Endpoint
- Determination of Maximum Tolerated Dose (MTD) of ET0111
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase I, open-label, multi-center, dose-finding study to assess the safety, pharmacokinetics, and preliminary efficacy of ET0111 in patients with advanced solid tumors. It is anticipated that approximately 37 subjects will be enrolled in the dose-escalation phase of the study. ET0111 will be administered orally once daily (QD) in 21-day treatment cycles.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
- •Aged at least 18 years at the time of ICF signature.
- •Histological or cytological confirmation of a solid tumor and have progressed despite standard therapy(ies), or are intolerant to standard therapy (ies), or have a tumor for which no standard therapy(ies) exists. Locally recurrent disease must not be amenable to surgical resection or radiotherapy with curative intent (patients who are considered suitable for surgical or ablative techniques following down-staging with study treatment are not eligible).
- •Estimated life expectancy of minimum of 12 weeks.
- •Patient with solid tumors must have at least 1 lesion, not previously irradiated, that can be accurately measured at pre-dose as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with Computerised Tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at ICF signature.
- •Males and Females of child-bearing potential must agree to use effective contraception from the time ICF signature until 12 weeks after the last dose. Females of childbearing potential include those who are premenopausal and those who are 2 years postmenopausal. Pregnancy tests for female of child-bearing potential must have a negative serum pregnancy test at Screening.
Exclusion Criteria
- •Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification..
- •Have current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
- •As judged by the investigator, any evidence of significant ophthalmological abnormalities including but not limited to history or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO, retinal macular degeneration, uncontrolled glaucoma, cataract or marked decrease in visual acuity, symptomatic severe dry eye, conjunctivitis, or corneal ulcer.
- •Prior bone marrow or organ transplantation
- •Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
- •Prior therapy with any irreversible FGFR inhibitor.
Arms & Interventions
Dose Escalation and Dose Expansion
ET0111 will be administered orally once daily in 21 days treatment cycles.
Intervention: ET0111
Outcomes
Primary Outcomes
Determination of Maximum Tolerated Dose (MTD) of ET0111
Time Frame: Approximately 2 years
MTD based on Number of participants with dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as any toxicity not attributable to the disease or disease-related processes under investigation, which occurs before the end of Cycle 1 (21 days as a cycle)
Recommended Phase 2 Dose (RP2D)
Time Frame: Approximately 2 years
RP2D may be the same dose level or lower than the determined MTD
Number of participants with adverse events
Time Frame: Approximately 2 years
All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments
Secondary Outcomes
- Overall survival(Approximately 2 years)
- Area under the curve(Approximately 2 years)
- T1/2(Approximately 2 years)
- Cmax(Approximately 2 years)
- Tmax(Approximately 2 years)
- Objective response rate(Approximately 2 years)
- Duration of response(Approximately 2 years)
- Disease Control Rate(Approximately 2 years)
- Progression-free survival(Approximately 2 years)