The purpose of this study is to evaluate the efficacy and safety of adjuvant autogene cevumeran plus atezolizumab and modified leucovorin, 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (mFOLFIRINOX) versus mFOLFIRINOX alone in participants with resected pancreatic ductal adenocarcinoma (PDAC) who have not received prior systemic anti-cancer treatment for PDAC and have no evidence of disease after surgery.
Inclusion Criteria:
* Histologically confirmed diagnosis of PDAC
* Pancreatic cancer tumor, lymph node, metastasis (TNM) pathological staging values of T1-T3, N0-N2, and M0 per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual
* Macroscopically complete (R0 or R1) resection of PDAC
* Unequivocal absence of disease after surgery as assessed by the investigator within 28 days prior to randomization
* CA19-9 level measured within 14 days prior to initiation of study treatment
* Interval of between 6 and 12 weeks since resection of PDAC
* Full recovery from surgery and ability to receive atezolizumab, autogene cevumeran, and mFOLFIRINOX in the investigator's judgment
* Adequate hematologic and end-organ function
* Female participants of childbearing potential must be willing to avoid pregnancy during the treatment period and for 28 days after the final dose of autogene cevumeran, for 9 months after the last dose of chemotherapy, and for 5 months after the final dose of atezolizumab. They must refrain from donating eggs for 9 months after the last dose of chemotherapy.
* Male participants with a female partner of childbearing potential or pregnant female partner must remain abstinent or use specified contraceptive methods during the treatment period and for 28 days after the final dose of autogene cevumeran and for 6 months after the last dose of chemotherapy. Men must refrain from donating sperm during this same period.
Exclusion Criteria:
* Prior adjuvant, neoadjuvant, or induction treatment for pancreatic cancer
* Plan for further adjuvant anti-cancer therapy for PDAC (e.g., radiotherapy and/or chemotherapy), not mandated per protocol, to be initiated after completion of mFOLFIRINOX treatment
* Absence of spleen; distal pancreatectomy with splenectomy is exclusionary
* Preexisting Grade \>/=2 neuropathy
* Known complete dihydropyrimidine dehydrogenase (DPD) deficiency including homozygous or compound heterozygous mutations of DPYD genetic locus associated with DPD deficiency
* Disorders of the colon or rectum, or postoperative complication leading to Grade \>/=2 diarrhea
* Pregnancy or breastfeeding
* Active or history of autoimmune disease or immune deficiency
* Treatment with brivudine, sorivudine, or their chemically-related analogues, which are inhibitors of DPD, within 4 weeks prior to initiation of study treatment
* Current or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) and/or uridine diphosphate glucoronosyltransferase 1A1 (UGT1A1).
