ET0038 treatment for patients with advanced solid tumors

A Phase I, Open-Label, Multi-Center Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of SHP2 Inhibitor ET0038 Monotherapy in Patients With Advanced Solid Tumors

This study is testing a new oral medication called ET0038 to see if it can safely help people with advanced solid tumors that have certain mutations.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Etern BioPharma (Shanghai) Co., Ltd (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 2 sites (Changsha, Hunan and 1 other locations)
• Trial ID: NCT05354843 on ClinicalTrials.gov

What this trial studies

This Phase I, open-label, multi-center study evaluates the safety, pharmacokinetics, and preliminary efficacy of ET0038, an oral medication, in patients with advanced solid tumors. The study consists of a dose-escalation phase and a dose-expansion phase targeting tumors with specific mutations that activate the RAS-MAPK pathway. Participants will receive ET0038 once daily in 21-day treatment cycles until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced solid tumors that have progressed despite standard therapies or for which no standard therapies exist.

Not a fit: Patients with solid tumors that are amenable to surgical resection or radiotherapy with curative intent may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have limited or no standard treatment alternatives.

How similar studies have performed: While this approach is novel in its specific targeting of the RAS-MAPK pathway with ET0038, similar studies targeting this pathway have shown promise in other contexts.

Eligibility criteria

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. Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
2. 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.
3. Prior bone marrow or organ transplantation
4. Prior treatment with ET0038 or a SHP2 inhibitor.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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).
10. 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)
11. Patient with history or presence of interstitial lung disease or interstitial pneumonitis.
12. 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.
13. Active infection including hepatitis B (Hepatitis B surface antigen \[HBsAg\] positive), and/or hepatitis C (HCV-RNA positive).
14. Active human immunodeficiency virus (HIV) infection (Patient with HIV positive and have well-controlled disease is exception).
15. 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.
16. Have a history or present active bleeding disease within 6 months at the time of ICF signature.
17. History of COVID-19 infections, or COVID-19 nucleic acid test positive at the time of ICF signature and/or prior to the first dose of study treatment.
18. Pregnant or Breast-feeding women

Where this trial is running

Changsha, Hunan and 1 other locations

• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• West China School of Medicine/West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Etern BioPharma (Shanghai) Co., Ltd — Etern BioPharma (Shanghai) Co., Ltd
• Study coordinator: Etern BioPharma (Shanghai) Co., Ltd

Conditions Advanced Solid Tumor