SHP2 Inhibitor ET0038 Monotherapy in Patients With Advanced Solid Tumors

NCT05354843 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: ET0038-101
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I, open-label, multi-center, dose-finding study to assess the safety, pharmacokinetics, and preliminary efficacy of ET0038 in patients with advanced solid tumors. It is anticipated that approximately 37 subjects will be enrolled in the dose-escalation phase of the study. ET0038 will be administered orally once daily (QD) in 21-day treatment cycles.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (3)

• RP2D of Phase 2 Dose of ET0038

  Find RP2D

  Approximately 2 years

• MTD of ET0038

  Fin MTD

  Approximately 2 years

• Number of participants with adverse events (AEs)

  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 Outcomes (9)

• Area under the curve

  Approximately 2 years

• Cmax

  Approximately 2 years

• Tmax

  Approximately 2 years

• T1/2

  Approximately 2 years

• Objective response rate

  Approximately 2 years

Other Outcomes (2)

• pERK

  Approximately 2 years

• NGS test of RTK/MAPK pathway genes

  Approximately 2 years

Study Arms (1)

Dose Escalation and Dose Expansion

EXPERIMENTAL

ET0038 will be administered orally once daily in 21 days treatment cycles.

Drug: ET0038

Interventions

ET0038 DRUG

ET0038 for oral administration

Dose Escalation and Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
• 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
• Prior treatment with ET0038 or a SHP2 inhibitor.
• Prior therapy with any investigational drugs or systemic anticancer treatment within 28 days (or a period of 5 'half-lives' of this investigational drugs or systemic anticancer treatment, whichever is the most appropriate and as judged by the investigator) at the time of ICF signature.
• Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days at the time of ICF signature, or planning radical radiation therapy while participating in the study.
• Prior major surgery (excluding placement of vascular access) within 28 days at the time of ICF signature, or planning for major surgery while participating in the study.
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE5.0) Grade 1 at the time of ICF signature.
• Any uncontrolled active infection requiring parenteral administration of antibiotics, antivirals, or antifungals at the time of ICF signature and/or within one week of Cycle 1 Day 1 (C1D1).
• Patient with a history of active pulmonary tuberculosis infection within 1 year prior to screening (as judged by investigator, active pulmonary tuberculosis infection more than 1 year and no evidence of active pulmonary tuberculosis at present will be considering eligible)
• Patient with history or presence of interstitial lung disease or interstitial pneumonitis.
• An active, or previously, autoimmune disease that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,autoimmune thyroid disease, vasculitis, and psoriasis etc.) or high risk to such diseases.
• Active infection including hepatitis B (Hepatitis B surface antigen \[HBsAg\] positive), and/or hepatitis C (HCV-RNA positive).
• Active human immunodeficiency virus (HIV) infection (Patient with HIV positive and have well-controlled disease is exception).
• Patient inability or unwillingness to comply with requirement for oral drug administration or presence of a gastro-intestinal condition, e.g., Refractory nausea and vomiting, inability to swallow the formulated product or previous significant bowel resection.

Sponsors & Collaborators

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

Study Sites (2)

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

RECRUITING

West China School of Medicine/West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Study Officials

• Etern BioPharma (Shanghai) Co., Ltd

  Etern BioPharma (Shanghai) Co., Ltd

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Etern BioPharma (Shanghai) Co., Ltd

CONTACT

86 021 50186958; jianhua.yi@eternbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Anticipated ET0038 Dose Escalation Schedule Cohort ET0038 dose at each treatment administration point 1\. SDL = 10 mg QD 2 .SDL × 2 = 20 mg QD 3. SDL × 4 = 40 mg QD 4 .SDL × 6 = 60 mg QD 5 .SDL × 8 = 80 mg QD Maximum Dose Level Abbreviations: QD=once a day; SDL=Starting Dose Level

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: April 29, 2022
• Study Start: October 27, 2021
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2025
• Last Updated: April 29, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)