A Phase I Study of Euthare-155008(ETH-155008) in AML and NHL Patients

NCT05758610 | Recruiting Phase 1 DMC

• 1 other identifier: ETH-155008- 101
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

This Trial is an open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ETH-155008 in subjects with AML and NHL who previously received standard treatment or are ineligible for standard treatment options.

Conditions

NHL, Adult; AML, Adult Recurrent

Outcome Measures

Primary Outcomes (3)

• Incidence and severity of adverse events

  Determine the safety of ETH-155008 in subjects with R/R AML and NHL

  At the end of Cycle 1 (each cycle is 28 days)

• Dose Limiting Toxicity (DLTs)

  Incidence of DLTs in the first treatment cycle of ETH-155008

  At the end of Cycle 1 (each cycle is 28 days)

• The RP2D(s) or the MTD of ETH-155008 in subjects with R/R AML and NHL

  The RP2D is the maximum tolerated dose (MTD) or less.

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (12)

• PK parameter of ETH-155008: Cmax

  At the end of Cycle 1 (each cycle is 28 days)

• PK parameter of ETH-155008: Tmax

  At the end of Cycle 1 (each cycle is 28 days)

• PK parameter of ETH-155008: AUC

  At the end of Cycle 1 (each cycle is 28 days)

• Disease evaluation of efficacy of ETH-155008: ORR

  12 months post first dosing

• Disease evaluation of efficacy of ETH-155008: CR

  12 months post first dosing

Study Arms (1)

ETH-155008

EXPERIMENTAL

Dose level: 20mg/day, 40mg/day, 60mg/day, 80mg/day, 100mg/day. Each dose level will recruit 1-6 subjects, taking ETH-155008 tablets once daily. Intervention: Drug: ETH-155008

Drug: ETH-155008

Interventions

ETH-155008 DRUG

ETH-155008 is an orally bioavailable, potent Pim-3 and CDK4/6 dual kinase inhibitor. Dosage form: 10mg, 20 mg and 40 mg, tablets. ETH-155008 tablets should be taken while fasting, either 1 hour before or 2 hours after a meal.

Also known as: Study drug

ETH-155008

Eligibility Criteria

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

You may qualify if:

• Be at least 18 years of age and \< 80 years old.
• Must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the trial and are willing to participate in the trial prior to any other trial-related assessments or procedures, and can communicated with investigators and are willing to comply with the protocol.
• Has histologically or cytologically confirmed relapsed and/or refractory acute myelocytic leukemia(AML) or non-Hodgkin's lymphoma(NHL) with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with ETH-155008 may be beneficial. In addition, the following disease-specific criteria outlined below must be met.
• For all indolent NHL (Follicular Lymphoma\[FL\], Marginal Zone Lymphoma\[MZL\] and Waldenström Macroglobulinemia\[WM\]), previously treated with at least 2 prior lines of systemic therapy with at least 1 line being an anti-cluster of differentiation antigen 20(anti-CD20) antibody-containing combination regimen. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), prior treatment with at least 2 lines of systemic therapy, including Bruton's tyrosine kinase(BTK) inhibitors or B-cell lymphoma-2(BCL-2) inhibitors, is required.
• For mantle cell lymphoma(MCL), prior treatment with at least 2 lines of systemic therapy (including a combination regimen of anti-CD20 antibodies and BTK inhibitors) and no other approved therapy considered more appropriate by the investigators.
• For aggressive B-NHL (diffuse large B cell lymphoma\[DLBCL\], highly malignant B-cell lymphoma\[HGBCL\], and primary mediastinal large B-cell lymphoma\[PMBCL\]), patients who can tolerate intensive therapy or autologous hematopoietic stem cell transplantation are required to have received standard second-line therapy in the past but have failed or relapsed. If patients cannot tolerate intensive therapy or autologous hematopoietic stem cell transplantation, they must have received standard first-line therapy in the past, but therapy failed or relapsed.
• For T-NHL, it is required to have been adequately treated with a systemic standard dose of drugs in the past without remission or recurrence.
• For AML, relapsed/refractory AML diagnosed according to the World Health Organization (WHO) classification in 2016, for which no standard treatment is available or for which standard treatment is not tolerated; According to Chinese Guidelines for the Diagnosis and Treatment of Relapsed and Refractory acute myeloid Leukemia (2021 Edition), the definition of relapsed and refractory is as follows:
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• Recurrent AML: recurrence of leukemia cells in peripheral blood or original cells in bone marrow ≥ 5% after CR (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration.
• Refractory AML: initial patients who failed to respond to 2 courses of treatment with standard protocols; Patients with CR relapse within 12 months after consolidation and intensive treatment; Patients who relapse after 12 months but fail to respond to conventional chemotherapy; Patients with two or more relapses; Extramedullary leukemia persists.
• For NHL, measurable lesions that meet the efficacy evaluation criteria for Lugano lymphoma (Cheson 2014) are required(at least one intranodular lesion longest diameter (LDi)﹥1.5 cm, or at least 1 extranodal lesion LDi﹥1 cm). For WM patients, immunoglobulin M(IgM) should be greater than 5g/L. For chronic lymphocytic leukemia(CLL) patients, monoclonal B lymphocytes greater than 5×109/L are required. For patients with AML, bone marrow primordial cells at baseline are required to be at least 5%.
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 (dose escalation cohorts) or ≤2 (dose expansion cohorts).
• For NHL, hematology laboratory parameters must be within the following ranges. Values must be without transfusions or growth factors for at least 7 days prior to the first dose of study drug ,
• Hemoglobin (HB) ≥80g/L; In case of bone marrow invasion, hemoglobin ≥60g/L is required (red blood cell infusion is allowed prior to initial administration).

You may not qualify if:

• Acute promyelocytic leukemia, acute mixed phenotypic leukemia, acute myeloid leukemia with Philadelphia chromosome (Ph chromosome) positive.
• AML with myeloid sarcoma.
• The central nervous system (CNS) is known to be involved.
• Previous solid organ transplantation.
• Previously received allogeneic hematopoietic stem cell transplantation.
• The patient received autologous hematopoietic stem cell transplantation (HSCT) within 3 months prior to initial administration of ETH-155008.
• Have an active autoimmune disease within the past 2 years that requires treatment with systemic immunosuppressive drugs (i.e., long-term corticosteroids, methotrexate, or tacrolimus).
• Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
• Cervical carcinoma of Stage ⅠB or less.
• Non-invasive basal cell or squamous cell skin carcinomas.
• Non-invasive, superficial bladder cancer.
• Prostate cancer with a current prostate-specific antigen(PSA) level \< 0.1 ng/mL.
• malignancy which in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 1 year before the first dose of study drug.
• Any curable cancer with a complete response(CR) of \> 2 years duration.
• Prior treatment with a cyclin dependent kinase 4 and 6(CDK4/6) or Pim inhibitor.

Sponsors & Collaborators

• Shengke Pharmaceuticals (Jiangsu) Limited, China: lead

Study Sites (2)

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

NOT YET RECRUITING

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute; Recurrence

Interventions

Drug Evaluation

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• James Zhang

  Shengke Pharmaceuticals (Jiangsu) Limited, China

  STUDY DIRECTOR

Central Study Contacts

James Zhang, Master

CONTACT

+86 512 68098859; james_zhang@shengketx.com

Study Design

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

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: March 7, 2023
• Study Start: November 4, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)