A Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Participants With Resected PDAC

Official title

A Phase II, Open-Label, Multicenter, Randomized Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX Versus mFOLFIRINOX Alone in Patients With Resected Pancreatic Ductal Adenocarcinoma

Overview

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.

Interventions

• Drug Autogene cevumeran
  Autogene cevumeran will be administered intravenously (IV) at a recommended dose at specified timepoints.
• Drug Atezolizumab
  Atezolizumab will be administered IV at a dose of 1680 milligrams (mg) at specified timepoints.
• Drug mFOLFIRINOX
  mFOLFIRINOX (oxaliplatin, leucovorin, irinotecan, 5-FU) will be administered IV at specified timepoints.

Primary outcome measures

• Disease Free Survival (DFS) [Time frame: From randomization to first recurrence of PDAC or first occurrence of new cancer, as determined by the investigator, or death from any cause (whichever occurs first), up to approximately 6 years]

Secondary outcome measures (4)

• DFS Rates at 12, 24, and 36 Months [Time frame: Months 12, 24, 36]
• Overall Survival (OS) [Time frame: From randomization to death from any cause (up to approximately 6 years)]
• OS Rates at 3 and 5 Years [Time frame: Years 3 and 5]
• Percentage of Participants With Adverse Events (AEs) [Time frame: Up to approximately 6 years]

Eligibility criteria

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 treatment initiation
• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 32 centers

• USC Norris Comprehensive Cancer Center — Los Angeles
• USC Norris Cancer Center — Newport Beach
• University of California, San Francisco (UCSF) — San Francisco
• University of California Los Angeles — Santa Monica
• St. Francis Hospital and Medical Center — Hartford
• Smilow Cancer Center — New Haven
• Yale Cancer Center — New Haven
• Smilow Cancer Hospital Care Center at Trumbull — Trumbull
• … and 24 more centers

Germany · 13 centers

• Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) — Berlin
• Katholisches Klinikum Bochum gGmbH;St. Josef-Hospital — Bochum
• Universitaetsklinikum Koeln — Cologne
• Universitätsklinikum Carl Gustav Carus Dresden — Dresden
• Universitätsklinikum Essen — Essen
• Krankenhaus Nordwest GmbH — Frankfurt
• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• Universitaetsklinikum Heidelberg — Heidelberg
• … and 5 more centers

Spain · 10 centers

• Institut Catala d?Oncologia Hospital Germans Trias i Pujol — Badalona
• Hospital Regional Universitario de Malaga — Málaga
• Clinica Universitaria de Navarra (CUN) — Pamplona/iruña
• Hospital Universitario Central de Asturias — Oviedo
• Hospital Universitario Vall d Hebron — Barcelona
• Hospital General Universitario Gregorio Marañon — Madrid
• Clinica Universitaria de Navarra de Madrid;Servicio de Hepatologia — Madrid
• Hospital Universitario Ramón y Cajal — Madrid
• … and 2 more centers

United Kingdom · 8 centers

Center list to be confirmed — check the primary protocol.

South Korea · 7 centers

• National Cancer Center (NCC) Hospital - Center for Liver and Pancreatobiliary Cancer — Goyang-si
• CHA Bundang Medical Center — Gyeonggi-do
• The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital) — Seocho
• Seoul National University Bundang Hospital — Seongnam-si
• Samsung Medical Center — Seoul
• Severance Hospital - Yonsei Cancer Center — Seoul
• University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center ( — Songpa-gu

Belgium · 5 centers

• Antwerp University Hospital — Edegem
• ULB Hôpital Erasme — Brussels
• AZ Maria Middelares — Ghent
• Universitair Ziekenhuis Gent — Ghent
• UZ Leuven — Leuven

France · 5 centers

• Centre Hospitalier Régional Universitaire de Lille — Lille
• Centre Leon Berard — Lyon
• Institut Paoli Calmettes — Marseille
• Institut de Cancérologie de Lorraine — Vandœuvre-lès-Nancy
• Gustave Roussy — Villejuif

Canada · 4 centers

• St Michael Hospital — Toronto
• Princess Margaret Cancer Center — Toronto
• Centre Hospitalier de l'Universite de Montreal - Notre - Dame Hos pital — Montreal
• Jewish General Hospital — Montreal

Netherlands · 3 centers

• Amsterdam UMC Location VUMC — Amsterdam
• UMC Radboud Nijmegen — Nijmegen
• Erasmus MC — Rotterdam

Sweden · 2 centers

• Sahlgrenska Universitetssjukhuset — Gothenburg
• … and 1 more center

Identifiers

NCT: NCT05968326 · GO44479 · 2022-502404-73-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗