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
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.
- 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
For Part B of study only: MSI-H patients are eligible to participate, irrespective of KRAS
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
- Adequate renal function, as defined by having creatinine clearance ≥30 mL/min
calculated by either Cockcroft-Gault or Modification of Diet in Renal Disease
- 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
- 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.
- Have ongoing toxicities >Grade 1 according to NCI CTCAE (National Cancer Institute
Common Terminology Criteria for Adverse Events) v5.0 (excluding alopecia and
- 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.