Key Inclusion Criteria:  Capable of giving signed informed consent Males and females age ≥ 18 years Phase 1/Dose Escalation : any histologically confirmed advanced or metastatic EGFR-positive malignancy for which all standard of care treatment options have been received and are no longer effective or are considered inappropriate at the discretion of the investigator. Phase 2a/Expansion : histologically confirmed advanced or metastatic EGFR positive malignancy of mCRC (EXP-1 cohort), SCCHN (EXP-2 cohort) or NSCLC (EXP-3 cohort).  Additional Criteria for Phase 2a/Expansion: subjects must have a disease history specific to their disease as listed below:  EXP-1: mCRC. Metastatic colorectal cancer (mCRC) MSI low/DNA mismatch repair proficient. Subjects must have received ≥ 1 lines of previous combination therapy and must have been exposed to oxaliplatin, irinotecan, a fluoropyrimidine, a VEGF targeting agent and, if considered appropriate by the treating physician, an EGFR targeted antibody. EXP-2: SCCHN. Subjects with advanced or metastatic SCCHN whose disease has progressed after having received ≥ 1 prior lines of therapy for advanced disease, which must have included platinum-based therapy, fluoropyrimidine, and an anti PD 1/PD-L1 antibody. EXP-3: NSCLC. Subjects with advanced or metastatic EGFR-expressing NSCLC (EGFR WT) whose disease has progressed after having received ≥ 1 prior lines of therapy for advanced disease. Subjects must have received at least a platinum-based doublet in combination with anti-PD1/PD-L1 antibody or must have received a platinum-based doublet followed by an anti-PD1/PD-L1 antibody. One or more measurable tumors lesions per RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate bone marrow, hepatic and renal function.  Key Exclusion Criteria:  Superior vena cava syndrome contra-indicating hydration Untreated or symptomatic central nervous system (CNS) metastases No resolution of specific toxicities related to any prior anti-cancer therapy to Grade ≤ 1 according to the NCI-CTCAE v.5.0 (except peripheral or motor neuropathy, lymphopenia and alopecia) Treatment with systemic anticancer therapy or an investigational device within 4 weeks (6 weeks if therapy was mitomycin C and/or nitrosoureas), or within 5 half-lives of the agent (if half-life is known and it is shorter) before the first dose of study treatment. Radiation therapy within 2 weeks before first dose of any study treatment or unresolved (NCI CTCAE v5.0 Grade > 1) toxicity from previous radiotherapy Clinically significant cardiovascular disease Major surgery within 4 weeks prior to any study treatment administration 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 prior to first dose of study treatment. 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 systemic immunosuppressive therapy A serious nonmalignant disease 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