Oncolytic Adenovirus CAdVEC and HER2 Specific CAR T Cells for the Treatment of Advanced or Refractory HER2 Positive Solid Tumors, VISTA Study

Inclusion Criteria

• PROCUREMENT: The patient has a histologically confirmed advanced refractory HER2 positive solid tumor, including but not limited to: head and neck squamous cell carcinoma; cancer of the salivary glands; lung cancer; breast cancer; bladder cancer; gastric cancer; esophageal cancer; colorectal cancer; and pancreatic adenocarcinoma. HER2 positivity is defined as >= 2+ staining by immunohistochemistry (IHC) with either the Food and Drug Administration (FDA)-approved CB11
• PROCUREMENT: Antibody (Leica) or anti HER2/neu (4B5) (VENTANA), which refers to greater than weak-to-moderate staining intensity in > 10% tumor cells
• PROCUREMENT: The disease must be deemed unsuitable for curative surgery, radiotherapy, systemic therapy, including checkpoint inhibitors, or any combination of the above modalities by the referring oncology physician and confirmed by the senior oncologists leading the protocol
• PROCUREMENT: Disease must have progressed after standard first line therapy, or without available effective treatment options. Patients are still eligible if they have failed more than one line of therapy
• PROCUREMENT: The patient must have at least one tumor site appropriate for intratumoral injection
• PROCUREMENT: The patient must have radiographically measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• PROCUREMENT: Life expectancy more than 12 weeks
• PROCUREMENT: The patient is >= 18 years of age, and able to understand and give informed consent to study related procedures and treatments
• TREATMENT: Histologically confirmed advanced refractory HER2 positive solid tumor, including but not limited to: head and neck squamous cell carcinoma; cancer of the salivary glands; lung cancer; breast cancer; bladder cancer; gastric cancer; esophageal cancer; colorectal cancer; and pancreatic adenocarcinoma. HER2 positivity is defined as >= 2+ staining by IHC with either the FDA-approved CB11 antibody (Leica) or anti HER2/neu (4B5) (VENTANA), which refers to greater than weak-to-moderate staining intensity in > 10% tumor cells
• TREATMENT: The disease must be deemed unsuitable for curative surgery, radiotherapy, systemic therapy, including checkpoint inhibitors, or any combination of the above modalities by the referring oncology physician and confirmed by the senior oncologists leading the protocol
• TREATMENT: Disease must have progressed after standard first line therapy, or without available effective treatment options. Patients are still eligible if they have failed more than one line of therapy
• TREATMENT: The patient must have at least one tumor site appropriate for intratumoral injection
• TREATMENT: The patient must have radiographically measurable disease as per RECIST 1.1
• TREATMENT: Absolute neutrophil count (ANC) >= 1.0 x 10^9/l (within 7 days prior to consent for treatment)
• TREATMENT: Hemoglobin >= 9 g/dl (within 7 days prior to consent for treatment)
• TREATMENT: Platelet count >= 100 x 10^9/l (within 7 days prior to consent for treatment)
• TREATMENT: Prothrombin time (PT) or partial thromboplastin time (PTT) =< 1.5 x upper limit of normal (ULN) unless the subject is receiving anticoagulation (within 7 days prior to consent for treatment)
• TREATMENT: Bilirubin < 2 ULN (within 7 days prior to consent for treatment)
• TREATMENT: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 ULN (within 7 days prior to consent for treatment)
• TREATMENT: Serum creatinine < 2 x the ULN or creatinine clearance > 60 mL/min (within 7 days prior to consent for treatment)
• TREATMENT: Left ventricular ejection fraction (LVEF) >= 55% (within 7 days prior to consent for treatment)
• TREATMENT: Prior HER2 targeted therapy is allowed if delivered at least 4 weeks prior to the enrollment (excluding DL1 and DL2)
• TREATMENT: Eastern Cooperative Oncology Group (ECOG) performance status 2 or less
• TREATMENT: Females of childbearing potential must have a negative pregnancy test and agree to use contraception during on-study protocol therapy
• TREATMENT: Male subjects with pregnant partner/female partner of childbearing potential agree to use barrier contraceptive during the study to minimize the risk of embryo-fetal exposure
• TREATMENT: The patient is >= 18 years of age, and able to understand and give informed consent to study related procedures and treatments.

Exclusion Criteria

• PROCUREMENT EXCLUSION CRITERIA
• History or evidence of active autoimmune disease requiring systemic corticosteroids (more than 10 mg/day), immunosuppressants or other disease modifying agents (except palliative radiation)
• Evidence of significant immunosuppressive conditions, such as the following: * Post organ transplant. * Diagnosis of human immunodeficiency virus (HIV) or other immunodeficiency disorders
• Diagnosis of other malignancies within 5 years except for cutaneous basal cell or squamous cell carcinoma, well-differentiated thyroid cancer, or localized prostate cancer
• Patients with known active hepatitis B or C infection
• Patient has had acute myocardial infarction within 6 months prior to consent for procurement
• Injectable tumor site is believed to incur a significant risk of major hemorrhage (e.g. located in the central nervous system [CNS] (brain), pulmonary parenchyma, and proximal to critical neurovascular structures). This is to be assessed by the treating and clinical team on a case-by-case basis
• Uncontrolled intercurrent illness including but not limited to psychiatric illness and or social situations that in the opinion of the investigator would compromise compliance of study requirements or put the patient at unacceptable risk
• Note: The procurement eligibility criteria are not applicable to patients on dose levels 1 and 2
• TREATMENT EXCLUSION CRITERIA
• Patients with any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (dose equivalent to prednisone > 10 mg/day), lymphodepleting antibodies, immunotherapy or cytotoxic agents. CNS metastasis requiring continuous high-dose steroids (dose equivalent to prednisone > 10 mg/day) or other active therapeutic intervention. This does not include stable, previously-treated brain metastases
• Patients at significant risk of airway compromise or other critical obstruction (e.g. bowel, ureter, etc.) in the event of possible post injection tumor inflammation based on the investigative team’s judgement
• History or evidence of active autoimmune disease requiring continuous systemic corticosteroids, immunosuppressants or other disease modifying agents
• Evidence of significant immunosuppressive conditions, such as the following: * Post organ transplant. * Diagnosis of HIV or other immunodeficiency disorders
• Diagnosis of other malignancies within 5 years except for cutaneous basal cell or squamous cell carcinoma, well-differentiated thyroid cancer, or localized prostate cancer.
• Patients with known active infectious disease, such as hepatitis B or C infection
• Patient has had acute myocardial infarction within 6 months prior to HER2. CAR T CELL infusion
• Patients with abnormal left ventricular function (LVEF < 55%)
• Injectable tumor site is believed to incur a significant risk of major hemorrhage (e.g located in the CNS (brain), pulmonary parenchyma, and proximal to critical neurovascular structures). This is to be assessed by the treating and clinical team on a case-by-case basis
• Pregnant or breastfeeding females
• Uncontrolled intercurrent illness including but not limited to psychiatric illness and or social situations that in the opinion of the investigator would compromise compliance of study requirements or put the patient at unacceptable risk.