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A Study to Find the Maximum Tolerated Dose (MTD) of SYN125 in People With Solid Tumors and the MTD of SYN125 With a Fixed Dose of SYN004 in People With Cancer of the Internal or External Lining of the Body.

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ClinicalTrials.gov Identifier: NCT04363242
Recruitment Status : Recruiting
First Posted : April 27, 2020
Last Update Posted : June 15, 2021
Sponsor:
Collaborator:
Synermore Biologics USA Limited
Information provided by (Responsible Party):
Synermore Biologics Co., Ltd.

Brief Summary:
A Phase 1 Dose Escalation Trial of SYN125 Single Agent in the Treatment of Solid Tumors and in Combination With Fixed Dose SYN004 in Patients With Cancer of the Internal or External Lining of the Body.

Condition or disease Intervention/treatment Phase
Epithelial Carcinoma Solid Tumor Biological: SYN125 Biological: SYN004 Phase 1

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) for solid tumors, and when it is used as a combined treatment with a fixed dose of SYN004 (Part B), in patients with epithelial cancers with EGFR (epithelial growth factor receptor) expressions.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Trial of SYN125 Single Agent in Solid Tumors and in Combination With Fixed Dose SYN004 in Patients With Epithelial Cancers With EGFR Expressions.
Actual Study Start Date : April 9, 2020
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : May 2022

Arm Intervention/treatment
Experimental: Part A
Dose escalation of SYN125. Each dose level (low, medium, high) 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.
Biological: SYN125
Administered by IV infusion

Experimental: Part B
Dose escalation of SYN125 administered with a fixed-dose of SYN004 (SYN004 will be administered immediately after SYN125 infusion is complete, if tolerated). Once cohorts with low and medium dose levels in Part A are completed and no DLTs are observed per cohort, Part B with the SYN125 low dose level + SYN004 will start and run in parallel with Part A. The high dose of SYN125 in a cohort in Part A will begin along with Part B.
Biological: SYN125
Administered by IV infusion

Biological: SYN004
Administered by IV infusion




Primary Outcome Measures :
  1. Part A: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to Day 28 ]
    Incidence of DLTs with single agent SYN125

  2. Part B: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to Day 28 ]
    Incidence of DLTs with SYN125 and fixed-dose SYN004 administered in combination


Secondary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: Up to Day 50 ]
    Incidence of Adverse Events (AEs)

  2. Incidence of Clinical Laboratory Abnormalities [ Time Frame: Up to Day 50 ]
    Defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0)

  3. 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 ]
    Serum concentration time profiles (Area under the serum concentration-time curve from time zero to the last measurable concentration) of SYN125 and SYN004

  4. Area under the serum concentration time-curve over the dosing interval [ Time Frame: Up to Day 106 ]
    Area under the serum concentration time-curve over the dosing interval of SYN125 and SYN004

  5. Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC0-inf) [ Time Frame: Up to Day 106 ]
    Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of SYN125 and SYN004

  6. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Day 106 ]
    Maximum Observed Plasma Concentration (Cmax) of SYN125 and SYN004

  7. Time to maximum observed serum concentration (Tmax) [ Time Frame: Up to Day 106 ]
    Time to maximum observed serum concentration (Tmax) of SYN125 and SYN004

  8. Terminal elimination half-life (t1/2) [ Time Frame: Up to Day 106 ]
    Terminal elimination half-life (t1/2) of SYN125 and SYN004

  9. Clearance [ Time Frame: Up to Day 106 ]
    Clearance of SYN125 and SYN004

  10. Volume of distribution at steady-state (Vss) [ Time Frame: Up to Day 106 ]
    Volume of distribution at steady-state (Vss) of SYN125 and SYN004



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Signed informed consent form.
  • Have documented diagnosis of recurrent or metastatic solid tumors for whom no standard treatment options are available (Part A only).
  • Have epithelial cancers which have endothelial growth factor receptor (EGFR) expressions (not necessarily mutated or over-expressed) (Part B only).

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 wash-out period will be 28 days from last dose of previous therapy except for palliative RT and smaller molecular oral therapeutic agents where 5 half-lives or 28 days, whichever is shorter, will apply (Part A and Part B).
  • Have evaluable disease per modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for immune based therapeutics (iRECIST).
  • 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.


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): NCT04363242


Locations
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United States, Kansas
University of Kansas Cancer Center, Clinical Research Center, 4350 Shawnee Mission Parkway, MS 6004 Recruiting
Fairway, Kansas, United States, 66205
Contact: Study Coordinator    913-945-7552    CTNurseNav@kumc.edu   
United States, Michigan
Henry Ford Health System, Henry Ford Hospital Recruiting
Brownstown, Michigan, United States, 48183
Contact: Karie Gignac, MD    313-916-7453    CTOP1@hfhs.org   
Contact    313-695-9808      
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Katlyn Kraft, CCRP    314-747-5440    katlyn.kraft@wustl.edu   
United States, Oklahoma
University of Oklahoma, Peggy and Charles Stephenson Cancer Center, 800 Northeast 10th Street Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Study Coordinator    405-271-8778    Phase1-Referrals@ouhsc.edu   
Sponsors and Collaborators
Synermore Biologics Co., Ltd.
Synermore Biologics USA Limited
Investigators
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Principal Investigator: Ding Wang, MD Henry Ford Hospital
Additional Information:
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Responsible Party: Synermore Biologics Co., Ltd.
ClinicalTrials.gov Identifier: NCT04363242    
Other Study ID Numbers: SYN125-001
First Posted: April 27, 2020    Key Record Dates
Last Update Posted: June 15, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Synermore Biologics Co., Ltd.:
Epithelial cancer
Epithelial Growth Factor Receptor expression
EGFR
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type