FGFR Inhibitor ET0111 Monotherapy in Patients With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

— FLIGHT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05522309
• Other study ID #: ET0111-101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 30, 2022
• Est. completion date: May 1, 2025

Study information

• Verified date: September 2022
• Source: Etern BioPharma (Shanghai) Co., Ltd
• Contact: Xin Luo
• Phone: 86 021 50186958
• Email: xin.luo[@]eternbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: May 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• ET0111
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).

Locations

Country	Name	City	State
China	Beijing Tongren Hospital,CMU	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Zhejiang university school of medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Qilu Hospital of Shandong University	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Etern BioPharma (Shanghai) Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	blood phosphorus	On treatment versus baseline comparison of blood phosphorus	Approximately 2 years
Other	ET0111 metabolites identification	ET0111 metabolites identify and analysis	Approximately 2 years
Other	NGS test of FGF/FGFR	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.	Approximately 2 years
Primary	Determination of Maximum Tolerated Dose (MTD) of ET0111	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)	Approximately 2 years
Primary	Recommended Phase 2 Dose (RP2D)	RP2D may be the same dose level or lower than the determined MTD	Approximately 2 years
Primary	Number of participants with adverse events	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	Approximately 2 years
Secondary	Area under the curve	Area under the plasma concentration time curve of ET0111	Approximately 2 years
Secondary	Cmax	Highest observed plasma concentration of ET0111	Approximately 2 years
Secondary	Tmax	Time of highest observed plasma concentration of ET0111	Approximately 2 years
Secondary	T1/2	Half life of ET0111	Approximately 2 years
Secondary	Objective response rate	Objective response rate	Approximately 2 years
Secondary	Duration of response	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.	Approximately 2 years
Secondary	Disease Control Rate	DCR is defined as the percentage of patients who achieved remission (PR+CR) and stabilization (SD) after treatment in evaluable cases.	Approximately 2 years
Secondary	Progression-free survival	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).	Approximately 2 years
Secondary	Overall survival	OS is defined as the time between the beginning of randomization and the death of the patient from any cause	Approximately 2 years