FGFR Inhibitor ET0111 Monotherapy in Patients With Advanced Solid Tumors (FLIGHT)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: ET0111

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xin Luo; Phone Number: 86 021 50186958; Email: xin.luo@eternbio.com
• Study Contact Backup: Name: Xiaoyan Li; Phone Number: +862150186958; Email: Xiaoyan.li@eternbio.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Not yet recruiting
      • Beijing Tongren Hospital,Cmu
      • Contact: Shurong Zhang
    • Beijing, Beijing, China
      • Recruiting
      • Chinese PLA General hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Yanqiao Zhang
  • Shandong
    • Jinan, Shandong, China
      • Not yet recruiting
      • Qilu Hospital of Shandong University
      • Contact: Yufeng Cheng
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Nong Xu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Dose Expansion; ET0111 will be administered orally once daily in 21 days treatment cycles.	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Recommended Phase 2 Dose (RP2D)	RP2D may be the same dose level or lower than the determined MTD	Approximately 2 years
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve	Area under the plasma concentration time curve of ET0111	Approximately 2 years
Cmax	Highest observed plasma concentration of ET0111	Approximately 2 years
Tmax	Time of highest observed plasma concentration of ET0111	Approximately 2 years
T1/2	Half life of ET0111	Approximately 2 years
Objective response rate	Objective response rate	Approximately 2 years
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood phosphorus	On treatment versus baseline comparison of blood phosphorus	Approximately 2 years
ET0111 metabolites identification	ET0111 metabolites identify and analysis	Approximately 2 years
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

Collaborators and Investigators

• Sponsor: Etern BioPharma (Shanghai) Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: August 27, 2022
• First Submitted That Met QC Criteria: August 27, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2022
• Last Update Submitted That Met QC Criteria: September 30, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ET0111-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No