Advanced Solid Tumor
Conditions
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.
Interventions
DRUGET0111
Oral capsules taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with ET0111 administered, once daily (QD).
Sponsors
Etern BioPharma (Shanghai) Co., Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) | Approximately 2 years | RP2D may be the same dose level or lower than the determined MTD |
| Determination of Maximum Tolerated Dose (MTD) of ET0111 | 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) |
| Number of participants with adverse events | 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
| Measure | Time frame | Description |
|---|---|---|
| Tmax | Approximately 2 years | Time of highest observed plasma concentration of ET0111 |
| T1/2 | Approximately 2 years | Half life of ET0111 |
| Duration of response | Approximately 2 years | DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first. |
| Disease Control Rate | Approximately 2 years | DCR is defined as the percentage of patients who achieved remission (PR+CR) and stabilization (SD) after treatment in evaluable cases. |
| Progression-free survival | Approximately 2 years | PFS is defined as the time between the onset of randomization and the onset (of any aspect) of tumor progression or death (from any cause). |
| Overall survival | Approximately 2 years | OS is defined as the time between the beginning of randomization and the death of the patient from any cause |
| Objective response rate | Approximately 2 years | Objective response rate |
| Area under the curve | Approximately 2 years | Area under the plasma concentration time curve of ET0111 |
| Cmax | Approximately 2 years | Highest observed plasma concentration of ET0111 |
Other
| Measure | Time frame | Description |
|---|---|---|
| blood phosphorus | Approximately 2 years | On treatment versus baseline comparison of blood phosphorus |
| NGS test of FGF/FGFR | Approximately 2 years | Next-generation sequencing (NGS) test will be performed with the tumor tissues or plasma ctDNA collected before ET0111 treatment, to detect FGF/FGFR gene alterations . Detected gene alteration data (including but not limited to mutation, insertion, deletion, amplification, translocation…) will be further analyzed for correlation with the anti-tumor activity of ET0111. |
| ET0111 metabolites identification | Approximately 2 years | ET0111 metabolites identify and analysis |
Countries
China
Contacts
Primary ContactXin Luo
Backup ContactXiaoyan Li
Outcome results
None listed