SHP2 Inhibitor ET0038 Monotherapy in Patients With Advanced Solid Tumors

NCT05525559 | Unknown Phase 1 FDA Drug

• 1 other identifier: ET0038-101 US
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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 34 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)

• Determination of Maximum Tolerated Dose (MTD) of ET0038

  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 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)

• Changes in phospho-ERK levels

  Approximately 2 years

• NGS test of RTK/MAPK pathway genes

  Approximately 2 years

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Oral capsules taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with ET0038 administered, once daily (QD).

Drug: ET0038

Interventions

ET0038 DRUG

ET0038 for oral administration

Dose Escalation

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:

• Primary central nervous system (CNS) tumor or uncontrolled CNS metastasis (severe clinical symptoms, bleeding, disease progression or steroid hormone use within 14 days before enrollment)..
• 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 (1)

BUMC - Mary Crowley Cancer Research Centers (MCCRC)

Dallas, Texas, 75230, United States

Location

Central Study Contacts

Xin Luo

CONTACT

86 021 50186958; xin.luo@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

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 1, 2022
• Study Start: November 1, 2022
• Primary Completion: November 1, 2024
• Study Completion: May 1, 2025
• Last Updated: September 1, 2022

Record last verified: 2022-08

Locations

US (1)