Safety and Preliminary Efficacy of SNK01 in Combination With Trastuzumab or Cetuximab in Subjects With Advanced HER2 or EGFR Cancers

Exclusion Criteria

• •Pregnant and/or lactating females. Women of childbearing potential must have negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days prior to receiving the first administration of the study drug(s) and a negative urine pregnancy test on Day 1 before first administration of the study drug(s). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
• •Life expectancy of less than three months.
• •Currently being treated with immunotherapy or received immunotherapy during the treatment regimen immediately prior to participation in this study.
• •Untreated for HER2- or EGFR-positive metastatic and/or unresectable malignancy OR have refused an available standard of care therapy appropriate for the specific tumor type for any reason other than for a known sensitivity, toxicity, or contraindication.
• •For EGFR-positive patients, first line cetuximab treatment stopped due to allergic response.
• •For EGFR-positive patients, superior vena cava syndrome contra-indicating hydration.
• •Untreated or symptomatic central nervous system (CNS) metastases. Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroid treatment for at least 4 weeks.
• •No resolution of specific toxicities related to any prior anti-cancer therapy to Grade ≤1 according to the NCI-CTCAE v.5.0 (except lymphopenia and alopecia).
• •Active peripheral or motor neuropathy of any CTCAE grade and due to any cause.
• •Known hypersensitivity or allergy or contraindication to at least one of the study drugs.
• •In case of previous chemotherapy, wash out period of less than 5 half-lives of treatment before study entry.
• •Clinically significant cardiovascular disease including:
• •1. Myocardial infarction within 3 months,
• •2. Congestive heart failure of the New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening LVEF assessment ≥ 45%,
• •3. Prolonged QT interval defined as screening corrected QT interval (QTc) \> 470 ms (Fridericia correction formula),
• •4. History of clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation),
• •5. History of Mobitz II 2nd degree or 3rd degree heart block without a permanent pacemaker in place,
• •6. Hypotension (systolic blood pressure \[BP\] \< 86 mmHg) or bradycardia with a heart rate \< 50 bpm,
• •7. Uncontrolled hypertension as indicated by a resting systolic BP \> 170 mmHg or diastolic BP \> 105 mmHg despite an optimal treatment,
• •Major surgery within 4 weeks prior first study drug administration or already planned during the study.
• •Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug(s). (Note: Subjects participating in an observational study are an exception to this criterion and may qualify for the study with Sponsor approval)
• •Any pulmonary, thyroid, renal, hepatic severe/uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol.
• •Active uncontrolled viral, fungal or bacterial infection requiring systematic therapy within 14 days of Day 1.
• •High fever or any active or unresolved infection.
• •Known history of testing positive for human immunodeficiency virus (HIV), and/or positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.
• •Autoimmune disease requiring therapy; immunodeficiency, or any disease process requiring immunosuppressive therapy.
• •A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
• •Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study.