Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of ES014 (Anti-CD39/TGF-β Bispecific Antibody) in Patients With Locally Advanced or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05381935
Recruitment Status : Not yet recruiting
First Posted : May 19, 2022
Last Update Posted : August 8, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: ES014 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, First-in-Human, Dose Escalation and Expansion, Phase 1 Study of ES014 in Subjects With Locally Advanced or Metastatic Solid Tumors
Estimated Study Start Date : April 21, 2023
Estimated Primary Completion Date : April 30, 2026
Estimated Study Completion Date : April 30, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 dose escalation
ES014 doses will be escalated in patients with advanced solid tumors with approximately 30 subjects.
Drug: ES014
ES014 is administered via intravenous infusion, once every 14 days, every 28 days as a treatment cycle for a maximum treatment duration per patient of 2 years.

Experimental: Part 2 dose expansion
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.
Drug: ES014
ES014 is administered via intravenous infusion, once every 14 days, every 28 days as a treatment cycle for a maximum treatment duration per patient of 2 years.




Primary Outcome Measures :
  1. The frequency and severity of adverse events of ES014 [ Time Frame: 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]


  2. Dose Limiting Toxicity of ES014 [ Time Frame: Assessed during first 28 days of treatment ]
    Evaluation of dose-limiting toxicity (DLT)

  3. Optimal biological dose (OBD) of ES014 [ Time Frame: 1-3 years ]
    The OBD of ES014 will be determined


Secondary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) of ES014 [ Time Frame: 1-3 years ]
    Maximum observed serum concentration (Cmax) of ES014 will be measured.

  2. Trough observed serum concentration (Ctrough) of ES014 [ Time Frame: 1-3 years ]
    Trough observed serum concentration (Ctrough)of ES014 will be measured.

  3. Area under the serum concentration time curve (AUC) of ES014 [ Time Frame: 1-3 years ]
    Area under the serum concentration time curve (AUC) of ES014 will be measured

  4. Time to Cmax (Tmax) of ES014 [ Time Frame: 1-3 years ]
    Time to Cmax (Tmax) of ES014 will be measured

  5. The terminal elimination half life of ES014 [ Time Frame: 1-3 years ]
    The terminal elimination half-life (t 1/2) of ES014 will be measured

  6. The clearance of ES014 [ Time Frame: 1-3 years ]
    A pharmacokinetic measurement of the volume of plasma from which ES014 is completely removed per unit time

  7. The volume of distribution of ES014 [ Time Frame: 1-3 years ]
    The amount of of ES014 in the body divided by the plasma concentration will be measured

  8. The immunogenicity of ES014 [ Time Frame: 1-3 years ]
    The presence and the frequency of anti-drug antibodies (ADA) against ES014 will be measured

  9. The antitumor activity of ES014 [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria

  1. To be eligible for study entry, subjects must satisfy all of the following criteria:
  2. Capable of giving signed informed consent.
  3. Part 1: Histological or cytological documentation of unresectable locally advanced or metastatic solid tumors, if 1) disease has progressed despite standard therapy, and no further standard therapy exists; or 2) standard therapy has proven to be ineffective or intolerable.

    Part 2: Histological or cytological documentation of PDAC (Cohort 2A), CRC (Cohort 2B), or NSCLC (Cohort 2C), with unresectable locally advanced or metastatic disease, if 1) disease has progressed despite standard therapy, and no further standard therapy exists; or 2) standard therapy has proven to be ineffective or intolerable.

  4. Provide tumor tissue samples (minimum 10 unstained FFPE slides) obtained from the initial diagnosis to study entry.
  5. At least one measurable lesion per RECIST v1.1.
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

    • Part 1: ECOG PS 0-1.
    • Part 2: ECOG PS 0-2.
  7. Life expectancy of at least 12 weeks.
  8. Adequate hematologic, hepatic, renal and coagulation functions per protocol
  9. Male and female subjects of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception

Key Exclusion Criteria

  1. Any prior therapy targeting CD39, CD73, adenosine A2A receptor, or TGF-β.
  2. Receipt of any investigational agents or devices within 4 weeks prior to the first dose of study drug.
  3. Prior treatment with the following therapies:

    1. Anticancer therapy within 30 days or 5 half-lives of the drug prior to the first dose of study drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered. Exception: hormonal and/or hormonal replacement therapy.
    2. A wash out of at least 2 weeks before the start of study drug for radiation to the extremities and 4 weeks for radiation to the chest, brain, or visceral organs is required.
  4. Prior allogeneic or autologous bone marrow transplantation or solid organ transplantation.
  5. Toxicity from previous anticancer treatment per protocol.
  6. Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug.
  7. Subjects who received transfusion of blood products (including platelets or red blood cells), G-CSF, GM-CSF, recombinant erythropoietin, or recombinant thrombopoietin within 14 days prior to the first dose of study treatment.
  8. Major surgery within 4 weeks prior to the first dose of study treatment.
  9. Live vaccine therapies within 4 weeks prior to the first dose of study treatment.
  10. Recent history of allergen desensitization therapy within 4 weeks prior to the first dose of study treatment.
  11. Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES014.
  12. Invasive malignancy or history of invasive malignancy other than disease under study within the last two years per protocol.
  13. CNS metastases.
  14. Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications per protocol.
  15. Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.
  16. Active infection requiring systemic therapy, known human immunodeficiency virus (HIV) infection, or positive test for hepatitis B active infection (HBsAg) or hepatitis C active infection (hepatitis C antibody).
  17. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
  18. History or evidence of cardiac abnormalities per protocol.

Information from the National Library of Medicine

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): NCT05381935


Contacts
Layout table for location contacts
Contact: Clinical Development (+86) 21 50651310 Clinical.Development@elpiscience.com
Contact: Clinical Development

Sponsors and Collaborators
Elpiscience Biopharma, Ltd.
Investigators
Layout table for investigator information
Study Director: Elpiscience Biopharma, Ltd. Elpiscience Biopharma, Ltd.
Layout table for additonal information
Responsible Party: Elpiscience Biopharma, Ltd.
ClinicalTrials.gov Identifier: NCT05381935    
Other Study ID Numbers: ES014-1001
First Posted: May 19, 2022    Key Record Dates
Last Update Posted: August 8, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms