Clinical trial NCT05522309: FGFR Inhibitor ET0111 Monotherapy in Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Etern BioPharma (Shanghai) Co., Ltd
Sponsor class: INDUSTRY
First posted: 2022-08-31
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
2. Aged at least 18 years at the time of ICF signature.
3. 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).
4. Estimated life expectancy of minimum of 12 weeks.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at ICF signature.
7. 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:

1. 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..
2. Have current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
3. 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
4. Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
5. Prior therapy with any irreversible FGFR inhibitor.

Primary outcomes:
measure: Determination of Maximum Tolerated Dose (MTD) of ET0111
timeFrame: Approximately 2 years
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Approximately 2 years
measure: Number of participants with adverse events
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Area under the curve
timeFrame: Approximately 2 years
measure: Cmax
timeFrame: Approximately 2 years
measure: Tmax
timeFrame: Approximately 2 years
measure: T1/2
timeFrame: Approximately 2 years
measure: Objective response rate
timeFrame: Approximately 2 years
measure: Duration of response
timeFrame: Approximately 2 years
measure: Disease Control Rate
timeFrame: Approximately 2 years
measure: Progression-free survival
timeFrame: Approximately 2 years
measure: Overall survival
timeFrame: Approximately 2 years
Other outcomes:
measure: blood phosphorus
timeFrame: Approximately 2 years
measure: ET0111 metabolites identification
timeFrame: Approximately 2 years
measure: NGS test of FGF/FGFR
timeFrame: Approximately 2 years
Locations:
city: Beijing
country: China
facility: Beijing Tongren Hospital,CMU
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang university school of medicine
state: Zhejiang
Study officials:
affiliation: Chinese PLA General Hospital
name: Jianming Xu
role: PRINCIPAL_INVESTIGATOR
References: