AzTrials
AzTrials

Advanced Solid TumorPhase 1NCT05381935

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

A Phase 1 study testing ES014 in people with Advanced Solid Tumor, run by Elpiscience Biopharma, Ltd..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor
What is being tested?
ES014
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
21 Apr 2023to 30 Apr 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To be eligible for study entry, subjects must satisfy all of the following criteria:
  • Capable of giving signed informed consent.
  • 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.
  • Provide tumor tissue samples (minimum 10 unstained FFPE slides) obtained from the initial diagnosis to study entry.
  • At least one measurable lesion per RECIST v1.1.
Show all 12Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • Part 1: ECOG PS 0-1.
  • Part 2: ECOG PS 0-2.
  • Life expectancy of at least 12 weeks.
  • Adequate hematologic, hepatic, renal and coagulation functions per protocol
  • Male and female subjects of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception

Who cannot join

  • Any prior therapy targeting CD39, CD73, adenosine A2A receptor, or TGF-β.
  • Receipt of any investigational agents or devices within 4 weeks prior to the first dose of study drug.
  • Prior treatment with the following therapies:
  • 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.
  • 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.
  • Prior allogeneic or autologous bone marrow transplantation or solid organ transplantation.
Show all 20Show fewer
  • Toxicity from previous anticancer treatment per protocol.
  • Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug.
  • 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.
  • Major surgery within 4 weeks prior to the first dose of study treatment.
  • Live vaccine therapies within 4 weeks prior to the first dose of study treatment.
  • Recent history of allergen desensitization therapy within 4 weeks prior to the first dose of study treatment.
  • Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES014.
  • Invasive malignancy or history of invasive malignancy other than disease under study within the last two years per protocol.
  • CNS metastases.
  • Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications per protocol.
  • Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.
  • 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).
  • 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).
  • History or evidence of cardiac abnormalities per protocol.

About this study

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

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.

Read the 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.

Being tested
ES014

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ES014Drug

    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.

  • ES014Drug

    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.

Study groups in NCT05381935
Study groupRoleWhat they receive
Part 1 dose escalationExperimentalES014 doses will be escalated in patients with advanced solid tumors with approximately 30 subjects.
Receives: Drug: ES014
Part 2 dose expansionExperimentalPart 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.
Receives: Drug: ES014

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The frequency and severity of adverse events of ES014

    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]

    Measured: 1-3 years

  2. Dose Limiting Toxicity of ES014

    Evaluation of dose-limiting toxicity (DLT)

    Measured: Assessed during first 28 days of treatment

  3. Optimal biological dose (OBD) of ES014

    The OBD of ES014 will be determined

    Measured: 1-3 years

Secondary outcomes (9)

  1. Maximum observed serum concentration (Cmax) of ES014

    Maximum observed serum concentration (Cmax) of ES014 will be measured.

    Measured: 1-3 years

  2. Trough observed serum concentration (Ctrough) of ES014

    Trough observed serum concentration (Ctrough)of ES014 will be measured.

    Measured: 1-3 years

  3. Area under the serum concentration time curve (AUC) of ES014

    Area under the serum concentration time curve (AUC) of ES014 will be measured

    Measured: 1-3 years

  4. Time to Cmax (Tmax) of ES014

    Time to Cmax (Tmax) of ES014 will be measured

    Measured: 1-3 years

  5. The terminal elimination half life of ES014

    The terminal elimination half-life (t 1/2) of ES014 will be measured

    Measured: 1-3 years

  6. The clearance of ES014

    A pharmacokinetic measurement of the volume of plasma from which ES014 is completely removed per unit time

    Measured: 1-3 years

  7. The volume of distribution of ES014

    The amount of of ES014 in the body divided by the plasma concentration will be measured

    Measured: 1-3 years

  8. The immunogenicity of ES014

    The presence and the frequency of anti-drug antibodies (ADA) against ES014 will be measured

    Measured: 1-3 years

  9. The antitumor activity of ES014

    Tumor response will be measured by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) by Investigator assessment

    Measured: 1-3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2022
  2. Study start21 Apr 2023 (estimated)
  3. Primary completion30 Apr 2026 (estimated)
  4. Study completion30 Apr 2026 (estimated)

Why it stopped: Sponsor's clinical development strategy adjustment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05381935
Sponsor's protocol ID
ES014-1001
Status last verified
Jan 2023
First submitted
11 May 2022
Last updated
31 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ES014 in people with Advanced Solid Tumor, run by Elpiscience Biopharma, Ltd..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 31 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The frequency and severity of adverse events of ES014 (time frame: 1-3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05381935.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in