Clinical Trials /

A Study to Find the Maximum Tolerated Dose of SYN125 in People With Advanced Colorectal and Head and Neck Cancer

NCT04363242

Description:

A Phase 1 Dose Escalation Trial of SYN125 Single Agent and in Combination With Fixed Dose SYN004 in Patients With Advanced Colorectal and Head and Neck Cancer

Related Conditions:
  • Colorectal Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Pharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Find the Maximum Tolerated Dose of SYN125 in People With Advanced Colorectal and Head and Neck Cancer
  • Official Title: A Phase 1 Dose Escalation Trial of SYN125 Single Agent and in Combination With Fixed Dose SYN004 in Patients With Advanced Colorectal and Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: SYN125-001
  • NCT ID: NCT04363242

Conditions

  • Colorectal Neoplasms
  • Head and Neck Neoplasms

Interventions

DrugSynonymsArms
SYN125Part A
SYN004Part B

Purpose

A Phase 1 Dose Escalation Trial of SYN125 Single Agent and in Combination With Fixed Dose SYN004 in Patients With Advanced Colorectal and Head and Neck Cancer

Detailed Description

      Humans have an immune system that can protect and fight infections and abnormal cells.
      T-cells are a type of cell produced by the body that can attack and kill cancer cells.
      Unfortunately, many cancer cells have ways preventing T-cells from working properly. SYN125
      and SYN004 can make T-cells work again. This is a study to find the maximum tolerated dose of
      SYN125 when it is used as a single treatment (Part A), and when it is used as a combined
      treatment with a fixed dose of SYN004 (Part B), in patients with advanced colorectal cancer
      and head and neck cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalDose escalation of SYN125. Each dose level will be tested in a cohort of 3 patients. If no dose-limiting toxicity (DLT) is observed in the 3 patients, dose escalation will continue to the next SYN125 dose level.
  • SYN125
Part BExperimentalDose escalation of SYN125 administered with a fixed-dose of SYN004 (SYN004 will be administered immediately after SYN125 infusion is complete, if tolerated). Each dose level of SYN125 will be tested in a cohort of 3 patients following that level of SYN125 being cleared in Part A. If no dose-limiting toxicity (DLT) is observed in the 3 patients, dose escalation will continue to the next level after that single SYN125 dose level has been cleared in Part A.
  • SYN125
  • SYN004

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent form.

          -  Have documented diagnosis of either:

               1. Recurrent or metastatic squamous-cell carcinoma of the head and neck (oral
                  cavity, pharynx, or larynx) not suitable for local curative treatment and for
                  whom no standard treatment options are available; or

               2. Metastatic colorectal cancer with either (i) KRAS wild-type or (ii)
                  EGFR-expressing tumors, or (iii) High levels of MicroSatellite Instability
                  (MSI-H), which has progressed following treatment with a fluoropyrimidine,
                  oxaliplatin, and irinotecan, or for whom no standard treatment options are
                  available.

        For Part B of study only: MSI-H patients are eligible to participate, irrespective of KRAS
        mutation status.

        Note: Prior EGFR (epidermal growth factor receptor) therapy and approved checkpoint
        inhibitor therapy are allowed but not required.

          -  Prior anti-PD-1 (programmed cell death 1), anti-PD-L1 (programmed death-ligand 1),
             anti-PD-L2 (programmed death-ligand 2), anti-cytotoxic T-lymphocyte antigen (CTLA-4)
             are allowed, where the last dose is at least 5 half-lives prior to Day 1 of study
             treatment, at the discretion of the investigator.

          -  Have evaluable disease per iRECIST criteria (modified Response Evaluation Criteria in
             Solid Tumors for immune based therapeutics).

          -  Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.

          -  Adequate bone marrow function, with absolute neutrophil count >1,500/µL, platelet
             count >75,000/µL, and hemoglobin >9g/dL (or 5.6 mmol/L).

          -  Adequate liver function with bilirubin <1.5 x the upper limit of normal (ULN) range,
             and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x the
             ULN.

          -  Adequate renal function, as defined by having creatinine clearance ≥30 mL/min
             calculated by either Cockcroft-Gault or Modification of Diet in Renal Disease
             equations.

          -  Adequate cardiac function, no clinically significant abnormalities assessed by
             electrocardiogram (ECG), and absence of significant cardiac disease.

          -  Negative serum pregnancy test within 24 hours prior to start of study drug in female
             patients of childbearing potential. Not applicable to patients unable to become
             pregnant, including those with bilateral oophorectomy and/or hysterectomy or
             postmenopausal.

          -  Patients of childbearing potential must be using highly effective contraception
             consisting of 2 forms of birth control (at least 1 of which must be a barrier method)
             during heterosexual intercourse, starting at screening and continuing throughout
             study, for a total of 31 weeks post-treatment completion.

        Exclusion Criteria:

          -  Have ongoing toxicities >Grade 1 according to NCI CTCAE (National Cancer Institute
             Common Terminology Criteria for Adverse Events) v5.0 (excluding alopecia and
             neuropathy).

          -  Have any contraindications to receiving cetuximab therapy, anti-PD-1, anti-PD-L1,
             anti-PD-L2, anti-CTLA-4 (anti-cytotoxic T-lymphocyte antigen) antibody, or other
             antibody or drug targeting T-cell co-stimulation or immune checkpoint pathways.

          -  Have known hypersensitivity to study drugs.

          -  Have undergone surgery and not recovered adequately from toxicities and/or
             complications from the intervention prior to starting study therapy; or have
             unresolved toxicity from prior radiation, chemotherapy, or other targeted treatment,
             including investigational treatment.

          -  Have clinically significant cardiac arrhythmia, unless well-controlled.

          -  Have clinically active central nervous system metastases and/or carcinomatous
             meningitis. Patients with previously treated brain or meningeal metastasis may
             participate and be eligible for treatment provided they are stable and asymptomatic,
             and have no evidence of new or enlarging brain metastases evaluated within 4 weeks
             prior to the first dose of study drug.

          -  Patients with history of human immunodeficiency virus (HIV) and:

               1. CD4+ T-cell count is ≤350 cells µL;

               2. History of AIDS-defining opportunistic infection within the past 12 months;

               3. Antiretroviral therapy <4 weeks and HIV viral load >400 copies/mL.

          -  Have participated in another investigational drug or device study within 4 weeks of
             the first dose of study drug.

          -  Female patient who is pregnant or breast feeding.

          -  Have signs or symptoms of organ failure, major chronic illnesses other than cancer, or
             any concomitant medical or social condition that, in the opinion of the investigator,
             make it undesirable for the patient to participate in the study, or that could
             jeopardize compliance with the protocol.

        Other protocol-defined inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Incidence of dose-limiting toxicities (DLTs)
Time Frame:Up to Day 28
Safety Issue:
Description:Incidence of DLTs with single agent SYN125

Secondary Outcome Measures

Measure:Incidence of Adverse Events (AEs)
Time Frame:Up to Day 50
Safety Issue:
Description:Incidence of Adverse Events (AEs)
Measure:Incidence of Clinical Laboratory Abnormalities
Time Frame:Up to Day 50
Safety Issue:
Description:Defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0)
Measure:Serum concentration time profiles (Area under the serum concentration-time curve from time zero to the last measurable concentration)
Time Frame:Up to Day 106
Safety Issue:
Description:Serum concentration time profiles (Area under the serum concentration-time curve from time zero to the last measurable concentration) of SYN125 and SYN004
Measure:Area under the serum concentration time-curve over the dosing interval
Time Frame:Up to Day 106
Safety Issue:
Description:Area under the serum concentration time-curve over the dosing interval of SYN125 and SYN004
Measure:Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC0-inf)
Time Frame:Up to Day 106
Safety Issue:
Description:Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of SYN125 and SYN004
Measure:Maximum Observed Plasma Concentration (Cmax)
Time Frame:Up to Day 106
Safety Issue:
Description:Maximum Observed Plasma Concentration (Cmax) of SYN125 and SYN004
Measure:Time to maximum observed serum concentration (Tmax)
Time Frame:Up to Day 106
Safety Issue:
Description:Time to maximum observed serum concentration (Tmax) of SYN125 and SYN004
Measure:Terminal elimination half-life (t1/2)
Time Frame:Up to Day 106
Safety Issue:
Description:Terminal elimination half-life (t1/2) of SYN125 and SYN004
Measure:Clearance
Time Frame:Up to Day 106
Safety Issue:
Description:Clearance of SYN125 and SYN004
Measure:Volume of distribution at steady-state (Vss)
Time Frame:Up to Day 106
Safety Issue:
Description:Volume of distribution at steady-state (Vss) of SYN125 and SYN004

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Synermore Biologics Co., Ltd.

Trial Keywords

  • Colorectal cancer
  • Head and neck cancer
  • Dose escalation

Last Updated

April 23, 2020