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.

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.

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.