An Open-Label, Multicenter, First-in-Human, Phase 1 Study of ES009 in Subjects With Locally Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- ES009
- Conditions
- Advanced Solid Tumor
- Sponsor
- Elpiscience Biopharma Australia Pty. Ltd.
- Enrollment
- 12
- Locations
- 4
- Primary Endpoint
- Recommended phase 2 dose (RP2D) of ES009
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of ES009 administered intravenously to subjects with advanced solid tumors.
Detailed Description
ES009 is a recombinant humanized IgG4 monoclonal antibody that specifically targets and blocks LILRB2. By reprograming suppressive myeloid cells into pro-inflammatory phenotypes, ES009 reshapes the immunosuppressive tumor microenvironment into an immune-favorable one to combat cancer development and progression. This is a 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 ES009 by evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of ES009 administered intravenously to subjects with advanced solid tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Capable of giving signed informed consent.
- •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 or is considered inappropriate.
- •At least one measurable lesion per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-
- •Life expectancy of at least 12 weeks.
- •Adequate hematologic, hepatic, renal and coagulation function 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 per protocol.
Exclusion Criteria
- •Any prior therapy targeting LILRB
- •Receipt of any investigational therapies within 28 days or 5 half-lives prior to the first dose of study drug.
- •Prior treatment with the following therapies:• Anticancer therapy within 28 days or 5 half-lives of the drug prior to the first dose of study drug, whichever is shorter. Exception: 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.
- •Toxicity from previous anticancer treatment per protocol.
- •Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug with certain exceptions.
- •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.
Arms & Interventions
Dose Escalation Cohort
ES009 monotherapy dose level will be escalated in participants with advanced solid tumors.
Intervention: ES009
Outcomes
Primary Outcomes
Recommended phase 2 dose (RP2D) of ES009
Time Frame: 1-3 years
The RP2D of ES009 will be determined.
The frequency and severity of adverse events of ES009
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.
Maximum tolerated dose (MTD) of ES009
Time Frame: 1-3 years
The MTD of ES009 will be determined.
Optimal biological dose (OBD) of ES009
Time Frame: 1-3 years
The OBD of ES009 will be determined.
Maximum administered dose (MAD) of ES009
Time Frame: 1-3 years
The MAD of ES009 will be determined.
Secondary Outcomes
- Area under the serum concentration time curve (AUC) of ES009(1-3 years)
- Trough observed serum concentration (Ctrough) of ES009(1-3 years)
- Time to Cmax (Tmax) of ES009(1-3 years)
- Immunogenicity of ES009(1-3 years)
- Preliminary antitumor activity of ES009(1-3 years)
- Maximum observed serum concentration (Cmax) of ES009(1-3 years)
- The terminal elimination half life of ES009(1-3 years)