Study of Personalized Tumor Vaccines (PCVs) and a PD-L1 Blocker in Patients With Pancreatic Cancer That Can be Treated With Surgery

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

Prior neoadjuvant treatment or radiation therapy for PDAC

Prior therapy with uPD-1 antibody or any other immune therapy

Borderline resectable, locally unresectable or metastatic PDAC

Pancreas tumor histology other than PDAC

Pregnancy, breastfeeding, or intending to become pregnant during the study or within 90 days after the last dose of study treatment

Life expectancy less than 12 weeks

Inability to comply with study and/or follow-up procedures

Any other malignancy for which the patient is undergoing active treatment which will be concurrent with the investigational agent in this study.

Patients with unresolved Clavien-Dindo \>/= Grade 3 (Section 20.0 APPENDICES ,Appendix 2) postoperative complications

Actie, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment

Active tuberculosis

Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection or subjects receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications

Known hypersensitivity or allergy to the active substance or to any of the excipients of RO7198457, atezolizumab, oxaliplatin, leucovorin, irinotecan, or fluorouracil

Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity. These include, but are not limited to:

* History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa)

* History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or multiple allergies

* History of the following within 6 months prior to RO7198457 administration: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysthythmia, or electrocardiogram (ECG) abnormality (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), cerebrovascular accident, transient ischemic attack,, or seizure disorder

History or autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following caveats:

* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible

* Patient with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible

Patients type 2 diabetes mellitus may be eligible

° Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible provided that they meet the following conditions:

Rash must cover less than 10% of the body surface area (BSA)

Disease is well controlled at baseline and only requires low potency topical steroids

No acute exacerbations of underlying condition within the last 12 months (e.g., not requiring psorlen and ultraviolet A (PUVA) radiation, methotrexate retinoids, biologic agents, oral calcineurin inhibitors, high potency, or oral steroids)

Treatment with systemic immunosuppressive medication (including but not limited to prednisone \>10mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-x antagonists) within 2 weeks prior to RO7198457 administration. Patients who have received acute, low-dose, systemic immunosuppressant medication (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the PI and Co-PI. The use of inhaled corticosteroids (e.g., fluticasone for chronic obstructive pulmonary disease) is allowed. The use of oral mineralocorticoids (e.g., flurocortisone for patients with orthostatic hypotension) is allowed. Physiologic doses of corticosteroids for adrenal insufficiency are allowed.

Subjects with allergies to IV contrast agents requiring pretreatment with corticosteroids will be excluded. Corticosteroids are immunosuppressive and may interfere with RO7198457 tolerability and efficacy. Given that there are serial contrast agent-dependent follow-up imaging studies built into the study which will overlap with vaccination, subjects who require pretreatment with corticosteroids prior to IV contrast administration will be excluded

History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchioloitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \[SCID\]) or combined T- and B-cell immunodeficiencies (e.g., T- and B-negative SCID, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency)

Prior allogeneic bone marrow transplantation or prior solid organ transplantation

Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug

Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse

Previous splenectomy

Administration of a live, attenuated vaccine within 4 weeks before RO7198457 administration or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to RO7198457 administration or at any time during the study, and for 90 days following the last study treatment

What this study is about