First-in Human (FIH) Trial of ETH-155008 in Subjects With B-NHL, CLL/SLL and AML

NCT04840784 | Terminated Phase 1 DMC

• 1 other identifier: ETH-155008-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

NHL; Leukemia

Outcome Measures

Primary Outcomes (4)

• Incidence and severity of adverse events

  Determine the safety of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML

  4 weeks

• Incidence and severity of Serious Adverse Event (SAEs)

  Determine the safety of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML

  4 weeks

• Dose Limiting Toxicity (DLTs)

  Incidence of DLTs starting from the first Dose period to the end of the first cycle of treatment of ETH-155008.

  4 Weeks

• The RP2D(s) or the MTD of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML

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

  4 weeks

Secondary Outcomes (8)

• PK parameter of ETH-155008: Cmax

  3 months

• PK parameter of ETH-155008: Tmax

  4 weeks

• PK parameter of ETH-155008: AUC

  3months

• Assess the PD of ETH-155008: Inhibition of Pim kinase

  6 months

• Assess the PD of ETH-155008: inhibition of FLT3

  6 months

Study Arms (1)

ETH-155008

EXPERIMENTAL

Dose level: 10mg/day, 20mg/day, 40mg/day, 60mg/day, 80mg/day, 100mg/day. Each dose level will recruit 3-6 subjects, taking ETH-155008 tablets once daily.

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

You may qualify if:

• Each potential subject must fulfil all of the following criteria to be enrolled in the study.
• 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. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard of care for the subject's disease.
• Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL, CLL/SLL or AML 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.
• a. For all indolent NHL (FL, MZL and Waldenström Macroglobulinemia), previously treated with at least 2 prior lines of systemic therapy with at least 1 line being an anti-CD20 antibody-containing combination regimen.
• b. For aggressive NHL (DLBCL, HGBCL, and PMBCL), received, or not eligible for high-dose chemotherapy containing anti-CD20 monoclonal antibodies and autologous stem cell transplantation with curative intent.
• c. For MCL, previously treated with at least 1 prior line of systemic therapy including an anti-CD20 antibody combination regimen, with no other approved therapies that would be more appropriate in the investigator's judgement.
• d. For CLL/SLL, relapsed or refractory with at least 2 prior lines of systemic therapy using different treatment regimens including BTK inhibitors or venetoclax.
• e. For AML, AML diagnosis according to the 2016 World Health Organization (WHO) classification who have received no more than 3 prior lines of therapy and with no available therapy.
• Has one of the following RB POSITIVE B-cell NHL subtypes or AML for the Dose Expansion:
• Aggressive NHL (DLCBL, HGBCL and PMBCL)
• MCL,
• AML Note: at screening, archived or fresh tumor tissue will be assayed by local sites and may need to be confirmed by a central lab later to evaluate Rb expression. Rb IHC staining intensity will be deemed positive if a staining level of 1+ or greater above background is identified.
• Presence of measurable or evaluable disease.

You may not qualify if:

• Any potential subject who meets any of the following criteria will be excluded from participating in the trial.
• Primary central nervous system (CNS) lymphoma or known CNS involvement at screening, unless treated and stable for ≥3 months with no need for steroids or anti-epileptic medications.
• Prior solid-organ transplantation.
• Prior treatment with allogenic stem cell transplant ≤6 months before the first dose of study drug, has evidence of graft versus host disease, or requires immunosuppressant therapy.
• Autologous HSCT within 3 months before the first dose of ETH-155008.
• Active autoimmune disease within the past 2 years requires systemic immunosuppressive medications (ie, chronic corticosteroid, 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 1B or less.
• Non-invasive basal cell or squamous cell skin carcinomas.
• Non-invasive, superficial bladder cancer.
• Prostate cancer with a current 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 CR of \> 2 years duration.
• Prior treatment with a CDK4/6 or Pim inhibitor.
• Known allergies, hypersensitivity, or intolerance to ETH-155008 or its excipients.

Sponsors & Collaborators

• Shengke Pharmaceuticals Pty Ltd: lead

Study Sites (5)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Alfred hospital

Melbourne, Victoria, 3004, Australia

Location

Epworth HealthCare

Richmond, Victoria, 3121, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Peninsula and South Eastern Haematologuy and Oncology Group

Melbourne, 3199, Australia

Location

MeSH Terms

Conditions

Leukemia

Interventions

Drug Evaluation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• James Zhang

  Shengke pharmacueticals Pty Ltd

  STUDY DIRECTOR

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: March 5, 2021
• First Posted: April 12, 2021
• Study Start: June 29, 2021
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: October 11, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)