First-in Human (FIH) Trial of ETH-155008 in Subjects With B-NHL, CLL/SLL and AML
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|ClinicalTrials.gov Identifier: NCT04840784|
Recruitment Status : Recruiting
First Posted : April 12, 2021
Last Update Posted : June 9, 2022
|Condition or disease||Intervention/treatment||Phase|
|NHL Leukemia||Drug: ETH-155008||Phase 1|
The primary objectives of this study are to evaluate the safety of ETH-155008 and to determine the recommended Phase 2 dose (RP2D) regimen or the maximum tolerated dose (MTD). Secondary objectives and endpoints will evaluate the PK and PD of ETH-155008 and preliminary clinical anti-tumor activity of ETH-155008 in subjects with R/R B-cell Non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) and acute myeloid leukemia (AML).
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. The study will be conducted in 2 parts: dose escalation (Part 1) and cohort expansion (Part 2). In the dose escalation, ETH-155008 will be administrated orally, once daily (QD) for 28 days at 6 dose levels ranging from 10 mg to 100 mg in 28-day cycles. Dose-limiting toxicity (DLT) will be assessed during the first treatment cycle and the maximum tolerated dose (MTD) will be identified. Addition subjects will be treated in the dose expansion at the commended phase 2 dose (RP2D).
During the study, safety will be monitored by the data review committee (DRC) at each dose escalation step and at regular intervals during cohort expansion. Continuous reassessment for DLTs will help minimize the potential risks associated with the study drug. Cumulative data from subsequent treatment cycles will also be monitored for late-onset toxicities.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||67 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1a/1b Dose Escalation and Dose Expansion, First-in-human, Open-Labeled Study of ETH-155008 in Subjects With Relapsed or Refractory B-cell NHL, CLL/SLL and AML|
|Actual Study Start Date :||June 29, 2021|
|Estimated Primary Completion Date :||May 2023|
|Estimated Study Completion Date :||May 2023|
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.
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.
Other Name: study drug
- Incidence and severity of adverse events [ Time Frame: 4 weeks ]Determine the safety of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML
- Incidence and severity of Serious Adverse Event (SAEs) [ Time Frame: 4 weeks ]Determine the safety of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML
- Dose Limiting Toxicity (DLTs) [ Time Frame: 4 Weeks ]Incidence of DLTs starting from the first Dose period to the end of the first cycle of treatment of ETH-155008.
- The RP2D(s) or the MTD of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML [ Time Frame: 4 weeks ]The RP2D is the maximum tolerated dose (MTD) or less.
- PK parameter of ETH-155008: Cmax [ Time Frame: 3 months ]maximum Concentration (Cmax) of ETH-155008
- PK parameter of ETH-155008: Tmax [ Time Frame: 4 weeks ]Time of First Occurrence of Cmax for ETH-155008
- PK parameter of ETH-155008: AUC [ Time Frame: 3months ]Area Under the Curve (AUC)
- Assess the PD of ETH-155008: Inhibition of Pim kinase [ Time Frame: 6 months ]Inhibition of Pim kinases
- Assess the PD of ETH-155008: inhibition of FLT3 [ Time Frame: 6 months ]inhibition of FLT3 (AML only)
- Assess the PD of ETH-155008: retinoblastoma protein [ Time Frame: 6 months ]Phosphorylation of upstream proteins: retinoblastoma protein (Rb)
- Assess the PD of ETH-155008:ribosomal protein [ Time Frame: 6 months ]Phosphorylation of upstream proteins: ribosomal protein (S6)
- Assess the PD of ETH-155008 [ Time Frame: 6 months ]Signal transducer and activator of transcription 5 (Stat5) after treatment with study drug.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04840784
|Contact: James Zhangemail@example.com|
|Australia, South Australia|
|Royal Adelaide Hospital||Recruiting|
|Adelaide, South Australia, Australia, 5000|
|Contact: Chris Giri, MD +61 8 7074 3290 Christine.firstname.lastname@example.org|
|Melbourne, Victoria, Australia, 3004|
|Contact: Nola Kennedy 03 9076 3451 email@example.com|
|Principal Investigator: Sushrut Patil, Dr|
|Richmond, Victoria, Australia, 3121|
|Contact: Costas Yannakou, Dr 0394836044 Costas.Yannakou@epworth.org.au|
|Principal Investigator: Costas Yannakou, Dr|
|Australia, West Australia|
|Royal Perth Hospital||Recruiting|
|Perth, West Australia, Australia, 6000|
|Contact: Megan Margaria +618244 8503 Megan.firstname.lastname@example.org|
|Principal Investigator: Michael Leahy, Prof|
|Peninsula and South Eastern Haematologuy and Oncology Group||Recruiting|
|Melbourne, Australia, 3199|
|Contact: Abert Goikhman +61391131307 email@example.com|
|Principal Investigator: Vinod Ganju, A/Prof|
|Study Director:||James Zhang||Shengke pharmacueticals Pty Ltd|