A Study of ES014 (Anti-CD39/TGF-β Bispecific Antibody) in Patients With Locally Advanced or Metastatic Solid Tumors
- Registration Number
- NCT05381935
- Lead Sponsor
- Elpiscience Biopharma, Ltd.
- Brief Summary
The purpose of this first-in-human, open-label, multicenter, non-randomized study designed to determine the maximum tolerated dose (MTD)/maximum administered dose (MAD), optimal biological dose (OBD), and recommended phase 2 dose (RP2D) of ES014 by evaluating the safety, tolerability, PK, pharmacodynamics, and preliminary clinical activity of ES014 administered intravenously to subjects with advanced solid tumors.
- Detailed Description
Adenosine and transforming growth factor-β (TGF-β) are two key immune suppressors in the tumor microenvironment (TME) that cause broad immune suppression resulting in resistance to current checkpoint inhibitor immunotherapies. The bifunctional antibody-fusion protein ES014 was created by fusing the TGF-β receptor II ectodomain to an antibody targeting human ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1, CD39, UniprotKB: P49961). ES014 simultaneously neutralizes autocrine/paracrine TGF-β and inhibits the enzymatic activity of CD39, which results in the stabilization of pro-inflammatory extracellular adenosine triphosphate (eATP) and the restoration of anti-tumor immunity by impairing the accumulation of immune suppressive adenosine and TGF-β within the TME.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 dose expansion ES014 Part 2 of the study will consist of 3 expansion cohorts for pancreatic ductal adenocarcinoma (Cohort 2A), NSCLC (Cohort 2B), and colorectal adenocarcinoma (Cohort 2C) with 10 subjects per expansion cohort respectively at the recommended optimal biological dose determined in Part 1 dose escalation. Part 1 dose escalation ES014 ES014 doses will be escalated in patients with advanced solid tumors with approximately 30 subjects.
- Primary Outcome Measures
Name Time Method The frequency and severity of adverse events of ES014 1-3 years Adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
\[Time Frame: 1-3 years\]Dose Limiting Toxicity of ES014 Assessed during first 28 days of treatment Evaluation of dose-limiting toxicity (DLT)
Optimal biological dose (OBD) of ES014 1-3 years The OBD of ES014 will be determined
- Secondary Outcome Measures
Name Time Method Maximum observed serum concentration (Cmax) of ES014 1-3 years Maximum observed serum concentration (Cmax) of ES014 will be measured.
Time to Cmax (Tmax) of ES014 1-3 years Time to Cmax (Tmax) of ES014 will be measured
The terminal elimination half life of ES014 1-3 years The terminal elimination half-life (t 1/2) of ES014 will be measured
Trough observed serum concentration (Ctrough) of ES014 1-3 years Trough observed serum concentration (Ctrough)of ES014 will be measured.
Area under the serum concentration time curve (AUC) of ES014 1-3 years Area under the serum concentration time curve (AUC) of ES014 will be measured
The clearance of ES014 1-3 years A pharmacokinetic measurement of the volume of plasma from which ES014 is completely removed per unit time
The volume of distribution of ES014 1-3 years The amount of of ES014 in the body divided by the plasma concentration will be measured
The immunogenicity of ES014 1-3 years The presence and the frequency of anti-drug antibodies (ADA) against ES014 will be measured
The antitumor activity of ES014 1-3 years Tumor response will be measured by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) by Investigator assessment