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

A First-in-Human Phase I, Open Label, Multiple Dose, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of Anti-BAFFR mAb, ESG206 in Subjects With B-cell Lymphoid Malignancies

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.

Study Overview

• Status: Not yet recruiting
• Conditions: B-cell Lymphoid Malignancies
• Intervention / Treatment: Drug: ESG206

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ESG206 dose level 1; ESG206 will be administered intravenously at dose level 1 every two weeks in a 28-day cycle.	Drug: ESG206; Administered via intravenous (IV) infusion
Experimental: ESG206 dose level 2; ESG206 will be administered intravenously at dose level 2 every two weeks in a 28-day cycle.	Drug: ESG206; Administered via intravenous (IV) infusion
Experimental: ESG206 dose level 3; ESG206 will be administered intravenously at dose level 3 every two weeks in a 28-day cycle.	Drug: ESG206; Administered via intravenous (IV) infusion
Experimental: ESG206 dose level 4; ESG206 will be administered intravenously at dose level 4 every two weeks in a 28-day cycle.	Drug: ESG206; Administered via intravenous (IV) infusion
Experimental: ESG206 dose level 5; ESG206 will be administered intravenously at dose level 5 every two weeks in a 28-day cycle.	Drug: ESG206; Administered via intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events	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.	First dose date up to last dose plus 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed plasma concentration	Up to 20 months
AUC0-inf	Area under the serum concentration time curve from time 0 extrapolated to infinity	Up to 20 months
Tmax	Time to maximum plasma concentration	Up to 20 months
T1/2	Half-life	Up to 20 months
Overall Response (OR)	Defined as complete response (CR) + partial response (PR)	Up to 20 months
Progression-free Survival (PFS)	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	Up to 20 months
ADA	Incidence of anti-drug antibodies	Up to 20 months

Collaborators and Investigators

• Sponsor: Shanghai Escugen Biotechnology Co., Ltd
• Collaborators: Escugen (Australia) Biotechnology Pty Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: February 18, 2022
• First Submitted That Met QC Criteria: February 28, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ESG206-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No