Study of VB10.NEO in Combination With Atezolizumab in Solid Tumors

Exclusion Criteria

• •Pregnant or breastfeeding, or intending to become pregnant during the trial or within 90 days after the last dose of VB10.NEO or 5 months after the last dose of atezolizumab, whichever occurs later
• •Significant cardiovascular disease such as, but not limited to, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
• •QT interval corrected through use of Fridericia's formula (QTcF) \>470ms demonstrated by at least 2 electrocardiograms (ECGs) \>30 minutes apart
• •Clinically significant liver disease including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse
• •Positive hepatitis B surface antigen (HBsAg) test at screening
• •Subjects with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive IgG antibody to hepatitis B core antigen) are eligible.
• •Positive hepatitis C virus (HCV) antibody test at screening
• •Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
• •Positive human immunodeficiency virus (HIV)-1 test at screening
• •Active tuberculosis
• •Any other diseases, metabolic dysfunction, physical examination finding, and/or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or may render the subject at high risk from treatment complications
• •Known primary immunodeficiencies
• •Active, or history of, autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• •Subjects with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the trial.
• •Subjects with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the trial.
• •Subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) are eligible for the trial provided all of the following conditions are met:
• •Rash must cover \<10% of body surface area
• •Disease is well controlled at baseline and requires only low potency topical corticosteroids
• •No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
• •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
• •Known allergy or hypersensitivity to any component of the VB10.NEO formulation.
• •History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on imaging conducted for tumor assessment at screening
• •History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• •History of drug-induced pneumonitis that was asymptomatic (defined by radiographic findings only) and reversible (without any anti-inflammatory therapies) is permitted.
• •Severe infection within 28 days prior to Cycle 1, Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• •Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease \[COPD\] exacerbation) are eligible for the trial.
• •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• •Subjects with indwelling catheters (e.g., PleurX) are allowed.
• •Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12 mg/dL, or corrected calcium \>ULN)
• •Major surgical procedure within 28 days prior to Cycle 1, Day 1, or anticipation of need for a major surgical procedure during the course of the trial
• •Prior allogeneic stem cell or solid organ transplantation
• •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 28 days or 5 drug-elimination half-lives (whichever is longer) prior to Cycle 1, Day 1
• •Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone \>7.5 mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, and tumor necrosis factor-alpha \[TNF-α\] antagonists) within 2 weeks prior to Cycle 1, Day 1 with the following exceptions:
• •Subjects who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the trial after medical monitor confirmation has been obtained
• •Subjects who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the trial.
• •Treatment with investigational therapy within 28 days prior to Cycle 1, Day 1
• •Live, attenuated vaccines are prohibited within 28 days prior to Cycle 1, Day 1, during atezolizumab treatment, and for 5 months after the final dose of atezolizumab
• •Vaccination with an approved COVID-19 vaccine that does not contain live, attenuated virus is permitted