Phase 1a/2a Dose Escalation Trial to Determine Safety, Tolerance, MTD, and Preliminary Antineoplastic Activity of AVID100, in Patients With Advanced or Metastatic Solid Tumors of Epithelial Origin

• Patients with a documented (histologically- or cytologically-proven) solid tumor epithelial carcinoma that is locally advanced or metastatic

• Patients with a malignancy that is either refractory to standard therapy, or for which no standard therapy is available

• Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor

• Phase 1a Dose-Escalation Cohorts: Patients with measurable or non-measurable disease according to RECIST, v1.1 criteria. To include patients reasonably likely to express EGFR.

• Patients with measurable disease according to RECIST, v1.1 criteria.

• Patients with triple negative breast cancer who are either EGFR 2+ or EGFR 3+ by validated IHC assay.

• Patients with squamous non-small cell lung cancer who are EGFR 3+ by validated IHC assay.

• Patients with squamous cell carcinoma of the head and neck who are EGFR 3+ by validated IHC assay.

• Patients whose malignancy is either refractory to standard therapy, or for which no standard therapy is available

• Patients whose malignancy is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor

‣ Patients to be Excluded (patients must not meet any of the following criteria Phase 1 only)

• Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a medically effective method of contraception.

• Patients with known central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required

• Patients with a malignancy other than that of epithelial origin

• Patients with hematologic abnormalities at baseline

• Patients with a significant cardiovascular disease or condition

• Patients with a significant ocular disease or condition

• Patients with a significant pulmonary disease or condition

• History of pneumonia within 6 months prior to the first study drug administration

• Patients with significant gastrointestinal (GI) abnormalities

⁃ Patients with non-healing wounds on any part of the body

‣ Patients to be Excluded (patients must not meet any of the following criteria Phase 2a only)

• Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a medically effective method of contraception.

• Patients with known central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required

• Patients with a malignancy other than EGFR-overexpressing triple negative breast cancer, squamous histology non-small cell lung cancer, or squamous cell carcinoma of the head and neck.

• Patients with hematologic abnormalities at baseline

• Patients with a significant cardiovascular disease or condition

• Patients with a significant ocular disease or condition

• Patients with a significant pulmonary disease or condition

• History of pneumonia within 6 months prior to the first study drug administration

• Patients with significant gastrointestinal (GI) abnormalities

⁃ Patients with non-healing wounds on any part of the body

⁃ Patients without measurable disease according to RECIST v1.1

⁃ Patients with an active second malignancy within the last 2 years prior to entry

‣ Drugs and Other Treatments to be Excluded

• Any antineoplastic agent for the primary malignancy (standard or investigational), without delayed toxicity, within 4 weeks, 5 plasma half-lives, or twice the duration of the biological effect, whichever is shortest, prior to first study drug administration and during study with the exception of: Nitrosoureas and nitrogen mustard within 6 weeks prior to first study drug administration and during study

• Any other investigational treatments during study. This includes participation in any medical device or other therapeutic intervention clinical trials.

• Radiotherapy for target lesions within 4 weeks prior to first study drug administration and during study

• Herbal preparations or related over-the-counter (OTC) preparations/supplements containing herbal ingredients aimed at treating the underlying malignancy within 2 weeks prior to first study drug administration and during study

• Strong inhibitors and/or inducers of cytochrome P450 (CYP) isoenzyme 3A4 within 2 weeks prior to first study drug administration and during study

• Immunosuppressive or systemic hormonal therapy within 2 weeks prior to first study drug administration and during study.

• Prophylactic use of hematopoietic growth factors within 1 week prior to first study drug administration and during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as clinically indicated