• Phase I: Maximum Tolerated Dose [ Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
  Number of patients with dose limiting toxicities
• Phase II: Percentage of patients with an Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)] [ Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
  Objective Response Rate as determined by RECIST which will be complete response (CR) + partial response (PR)

• Phase I: Number of patients with Dose Limiting Toxicities [ Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
• Phase I: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. [ Time Frame: Every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
• Phase I: Number of participants who developed measurable anti-drug antibodies [ Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
• Phase II: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. [ Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
• Phase II: Duration of response (DOR) in patients who responded as determined by RECIST [ Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
• Phase II: Number of participants who developed measurable anti-drug antibodies [ Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
• Phase II: Progression Free Survival (PFS) [ Time Frame: 2 years from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
  Kaplan Meier Curve for survival without progression in patients who responded to treatment
• Phase II: Overall Survival (OS) [ Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
  Kaplan Meier Curve for survival in all enrolled patients
• Phase I and II: Phase I and II Maximum observed serum or plasma concentration (Cmax). [ Time Frame: 84 Days from date of first dose ]
• Phase I and II: Clearance (CL). [ Time Frame: 84 Days from date of first dose ]
• Phase I and II: Area under the serum or plasma concentration time curve from 0 to infinity (AUC[0-∞]). [ Time Frame: 84 Days from date of first dose ]
• Phase I and II: Terminal phase elimination half life (t½). [ Time Frame: 84 Days from date of first dose ]
• Phase I and II: Volume of distribution at terminal phase (Vz). [ Time Frame: 84 Days from date of first dose ]
• Phase I and II: Volume of distribution at steady state (Vss). [ Time Frame: 84 Days from date of first dose ]

• HER2-positive Breast Cancer
• HER2 Gene Mutation
• HER-2 Gene Amplification
• HER2 Positive Gastric Cancer
• Salivary Gland Cancer
• Salivary Gland Tumor
• Salivary Gland Carcinoma
• Salivary Gland Neoplasms
• Lung Cancer
• Colo-rectal Cancer
• Rare Diseases
• Solid Tumor
• Recurrent Gastric Cancer
• Recurrent Colon Cancer
• Recurrent Breast Cancer
• Head and Neck Cancer
• Head and Neck Carcinoma
• Bladder Cancer
• Cervical Cancer
• Liver Cancer
• Bile Duct Cancer
• Urologic Cancer
• Pancreatic Cancer
• Prostate Cancer
• Recurrent Prostate Cancer
• Rectal Cancer
• Recurrent Ovarian Carcinoma
• Recurrent Renal Cell Cancer
• Rectal Cancer Stage II
• Rectal Cancer Stage I
• Rectal Cancer Stage III
• Skin Cancer
• Mouth Cancer
• Lip Cancer Stage I
• Tongue Cancer
• Breast Neoplasm Malignant Primary
• Larynx Cancer
• Tonsil Cancer
• Palate Cancer
• Mucoepidermoid Carcinoma
• Primary Peritoneal Carcinoma
• Mucinous Adenocarcinoma Gastric
• Mucinous Breast Cancer Recurrent
• Cholangiocarcinoma

• Experimental: Phase I: Dose Escalation
  Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
  Intervention: Drug: A166
• Experimental: Phase II: • Cohort 1
  HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) breast cancer. Treatment with A166 at recommended Phase II dose.
  Intervention: Drug: A166
• Experimental: Phase II: • Cohort 2
  HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) gastric cancer. Treatment with A166 at recommended Phase II dose.
  Intervention: Drug: A166
• Experimental: Phase II: • Cohort 3
  HER2 low expressing (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) breast cancer. Treatment with A166 at recommended Phase II dose.
  Intervention: Drug: A166
• Experimental: Phase II: • Cohort 4
  All cancers other than breast cancer with low HER2 expression (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) and HER2 positive (IHC2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer. Treatment with A166 at recommended Phase II dose.
  Intervention: Drug: A166

Inclusion Criteria:

Phase I

Patients must meet the following criteria for inclusion into the study:

1. Patients must be able to provide documented voluntary informed consent.
2. Male or female patient ≥ 18 years.
3. Histologically documented, incurable, locally advanced or metastatic cancer.
4. Evaluable or measurable HER2 positive (by ISH or NGS) disease or HER2 expressing disease. HER2 expressing is defined in this protocol as HER2 expression of ≥ 1+ determined by validated IHC.
5. Patients should have no available therapy likely to convey clinical benefit.
6. Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.
7. Serum bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
8. Creatinine clearance ≥ 50 mL/min calculated by Cockroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 24 hour urine collection is not required but is allowed.
9. ECOG Performance Status ≤ 1.
10. Women of childbearing potential and men must agree to use an approved method of birth control (e.g., hormonal, barrier) while receiving study drug, and for at least 7 months after the last dose of study drug. Women are excluded from birth control if they had had tubal ligation or a hysterectomy.
11. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

Phase II

Patients must meet the following criteria for inclusion into the study:

1. Patients must be able to provide documented voluntary informed consent.
2. Male or female patient ≥ 18 years.
3. Histologically documented, incurable, locally advanced or metastatic cancer.
4. Evaluable or measurable HER2 positive (by ISH or NGS) disease or HER2 expressing disease. HER2 expressing is defined in this protocol as HER2 expression of ≥ 1+ determined by validated IHC.

5. Regarding previous therapy:

   5.1. Cohort 1: HER2 positive (IHC 2+ with FISH confirmation and Immunohistochemistry (IHC 3+) breast cancer: patients should have progressed after at least 2 previous HER2 directed regimens in metastatic disease with approved therapies.

   5.2. Cohort 2: HER2 positive (IHC 2+ with FISH confirmation and IHC 3+) gastric cancer: patients should have progressed after at least 1 previous HER2 directed regimens in metastatic disease with approved therapies.

   5.3. Cohort 3: HER2 low expressing (IHC 1+ and IHC 2+ without FISH confirmation) breast cancer: patients should have no available therapy likely to convey clinical benefit.

   5.4. Cohort 4: all cancers other than breast cancer with low HER2 expression (IHC 1+ and IHC 2+ without FISH confirmation) and HER2 positive (IHC 2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer: patients should have no available therapy likely to convey clinical benefit.

6. Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.
7. Serum bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
8. Creatinine clearance ≥ 50 mL/min calculated by Cockroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 24 hour urine collection is not required but is allowed.
9. ECOG Performance Status ≤ 1.
10. Women of childbearing potential and men must agree to use an approved method of birth control (e.g., hormonal, barrier) while receiving study drug, and for at least 7 months after the last dose of study drug. Women are excluded from birth control if they had had tubal ligation or a hysterectomy.
11. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

Exclusion Criteria:

Phase I:

1. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
2. History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
3. History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
4. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
5. Require supplemental oxygen for daily activities.
6. Documented Grade ≥ 2 peripheral neuropathy.
7. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
8. Any experimental therapy within 4 weeks of first infusion of study drug.
9. Any major surgical procedure within 4 weeks of first infusion of study drug.
10. Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
11. Have known prior positive test results for human immunodeficiency virus.
12. Uncontrolled hypertension or diabetes.
13. Pregnancy or lactation.
14. Resting corrected QT interval (QTc) > 470 ms at baseline.
15. Left ventricular ejection fraction (LVEF) < 45% determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
16. Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent.

Phase II:

1. Any patient who was treated in the Phase I part of this study.
2. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
3. History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
4. History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
5. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
6. Require supplemental oxygen for daily activities.
7. Documented Grade ≥ 2 peripheral neuropathy.
8. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
9. Any experimental therapy within 4 weeks of first infusion of study drug.
10. Any major surgical procedure within 4 weeks of first infusion of study drug.
11. Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
12. Have known prior positive test results for human immunodeficiency virus.
13. Uncontrolled hypertension or diabetes.
14. Pregnancy or lactation.
15. Resting QTc > 470 ms at baseline.
16. LVEF < 45% determined by ECHO or MUGA scan.
17. Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent.