| Eligibility |
Inclusion Criteria:
- Subjects must be >/= 18 years of age at time of informed consent
- Able to comply with the study protocol, in the investigator's judgment
- Subjective with radiographically resectable primary pancreatic tumors with
radiographic features consistent with adenocarcinoma will be evaluated for surgical
resection
- Tumors must be radiographically resectable, defined as:
- A clear fat plane around the celiac and superior mesenteric arteries
- patent superior mesenteric and portal veins without primary tumor involvement
- No encasement of the superior mesenteric vein or portal veins
- No encasement of the superior mesenteric or hepatic arteries
- No metastatic disease
- No extra-regional nodal disease
- Subjects with histologically confirmed resected ductal pancreatic adenocarcinoma with
macroscopic complete resection (R0 and R1) will be selected for neoantigen vaccine
creation. Subjects with neuroendocrine (and mixed type) tumors are excluded
- Pancreatic cancer surgical staging: T 1-3, N0-2, M0
° Per AJCC 8th edition staging
- Performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Scale of
Performance Status (Section 20.0 APPENDICES, Appendix1)
- Subjects must not have had prior chemotherapy, radiation therapy, or immunotherapy for
PDAC
- Subjects must be able to read, understand, and sign informed consent
- Women of childbearing potential must have a negative serum or urine pregnancy test
within 14 days prior to study initiation
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures that result in a failure rate
of less than (<) 1% per year during the treatment period and for at least 5 months
after the last dose of atezolizumab and for at least 90 days after the last dose of
RO7198457. A woman is considered to be of childbearing potential if she is
postmenarcheal, has not reached a postmenopausal state (>/= 12 continuous months of
amenorrhea with no identified cause other than menopause), and has not undergone
surgical sterilization (removal of ovaries and/or uterus)
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
a condom during the entire study period and up to 90 days after last administration of
RO7198457. Male participants should not donate sperm for 90 days after the last dose
of RO7198457
- Examples of contraceptive methods with a failure rate of <1% per year include
bilateral tubal ligation, male sterilization and established proper use of hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and
copper intrauterine devices
- Hormonal contraceptive methods must be supplemented by a barrier method plus
spermicide
- The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception
Exclusion Criteria:
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
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