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A First-in-Human Phase I Study of ESG206 in Subjects With B-cell Lymphoid Malignancies

Phase 1
Not yet recruiting
Conditions
B-cell Lymphoid Malignancies
Interventions
Registration Number
NCT05263739
Lead Sponsor
Shanghai Escugen Biotechnology Co., Ltd
Brief Summary

This is a first-in-human phase I, multicenter, open label, sequential-cohort, dose escalation study of ESG206. The purpose is to evaluate the clinical safety, tolerability, PK, and preliminary efficacy and to establish the MTD, if any, and RP2D(s) of ESG206 in adult subjects with B lymphoid malignancies.

Detailed Description

This is a first-in-human phase I, multicenter, open label, sequential-cohort, dose escalation study of ESG206. The study will follow a modified 3+3 dose escalation scheme. Dose escalation will continue until identification of MTD or the predicted efficacy dose in the event that a MTD is not identified due to paucity of DLTs. Toxicity including dose-limiting toxicity (DLT) observed in Cycle 1 of the first 28 days will be used to determine escalation to the next dose level as described below.

Five dose levels are planned. Dose choosing will be determined by the SMC and the sponsor based on the pharmacokinetics, tolerability and preliminary antitumor activities, as well as other available data.

Subjects will be monitored for safety, tolerability, and efficacy throughout the study.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
12
Inclusion Criteria
  • Willing and able to provide written informed consent for the trial.
  • Male or female and at least 18 years of age.
  • Subjects must have a histologically confirmed (or documented), incurable B-cell hematologic malignancy that had progressed despite standard of care therapy and for which there was no alternative therapy of proven benefit or no effective standard therapy is available or tolerable.
  • Measurable or evaluable Disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Subject must have adequate organ function.
Exclusion Criteria
  • Has had prior chemotherapy, targeted therapy, immunotherapy or any other agents used as systemic treatment for cancer, within 14 days before first dosing.
  • Had major surgery within 4 weeks before first dosing.
  • Had undergone an autologous stem cell transplant within 100 days before first dosing.
  • Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, or renal disease).
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product or excipients.
  • Pregnant or breastfeeding women.
  • Unwillingness or inability to follow the procedures outlined in the protocol.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
ESG206 dose level 2ESG206ESG206 will be administered intravenously at dose level 2 every two weeks in a 28-day cycle.
ESG206 dose level 4ESG206ESG206 will be administered intravenously at dose level 4 every two weeks in a 28-day cycle.
ESG206 dose level 1ESG206ESG206 will be administered intravenously at dose level 1 every two weeks in a 28-day cycle.
ESG206 dose level 5ESG206ESG206 will be administered intravenously at dose level 5 every two weeks in a 28-day cycle.
ESG206 dose level 3ESG206ESG206 will be administered intravenously at dose level 3 every two weeks in a 28-day cycle.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Experiencing Any Treatment Emergent Adverse EventsFirst dose date up to last dose plus 30 days

Treatment-emergent adverse events (TEAEs) were defined as: Any AE that happens after treatment initiation,.or AE that was present at time of treatment initiation but worsened after treatment initiation, or AE that was present and resolved prior to treatment and reappeared after treatment initiation after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0.

Secondary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS)Up to 20 months

Defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause

ADAUp to 20 months

Incidence of anti-drug antibodies

AUC0-infUp to 20 months

Area under the serum concentration time curve from time 0 extrapolated to infinity

TmaxUp to 20 months

Time to maximum plasma concentration

Overall Response (OR)Up to 20 months

Defined as complete response (CR) + partial response (PR)

CmaxUp to 20 months

Maximum observed plasma concentration

T1/2Up to 20 months

Half-life

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