B-cell Lymphoid Malignancies
Conditions
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.
Interventions
DRUGESG206
Administered via intravenous (IV) infusion
Sponsors
Escugen (Australia) Biotechnology Pty Ltd
Shanghai Escugen Biotechnology Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Any Treatment Emergent Adverse Events | First 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
| Measure | Time frame | Description |
|---|---|---|
| AUC0-inf | Up to 20 months | Area under the serum concentration time curve from time 0 extrapolated to infinity |
| Tmax | Up to 20 months | Time to maximum plasma concentration |
| T1/2 | Up to 20 months | Half-life |
| Cmax | Up to 20 months | Maximum observed plasma concentration |
| 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 |
| ADA | Up to 20 months | Incidence of anti-drug antibodies |
| Overall Response (OR) | Up to 20 months | Defined as complete response (CR) + partial response (PR) |
Outcome results
None listed