Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial
Abstract
Abstract In this phase I study, we test a pooled synthetic long peptide vaccine targeting the six KRAS mutations (G12V, G12A, G12R, G12C, G12D, G13D) with ipilimumab and nivolumab in resected pancreatic adenocarcinoma. Co-primary endpoints include safety and maximal percent change of IFNγ-producing mutant KRAS T cell responses in the blood within 17 weeks. Secondary endpoints include disease-free survival, overall survival, and maximal percent change of IFNγ-producing mutant KRAS T cell responses at any time after vaccination. Vaccine-related adverse events are grade 1-2. 11/12 and 10/12 patients generate a significant increase in average T cell response to 6 mutant KRAS antigens and tumor-specific response, respectively. Immunophenotyping demonstrate Th1 CD4 central memory and effector memory T cells, and CD8 effector memory T cells at a lower frequency. The vaccine also generates cross-reactive T cells that recognize more than one mutant KRAS antigen. These findings support the safety and diverse anti-tumor immunity of mutant KRAS vaccines (NCT04117087).
Article Details
Authors (39)
Amanda L. Huff
S. Daniel Haldar
Alexander A. Girgis
Hejia Henry Wang
Ludmila Danilova
Thatcher Heumann
Maureen Berg
Yuxuan Wang
Lalitya Andaloori
Alexei Hernandez
Gabriella Longway
Benjamin Barrett
Zirui Zhu
Emily Davis-Marcisak
Christopher Thoburn
James Leatherman
Sarah Mitchell
Jae W. Lee
Daniel H. Shu
Maximillian F. Konig
Brian J. Mog
Ludwig Center for Cancer Genetics and Therapeutics and Lustgarten Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine
Janelle Montagne
Erin M. Coyne
Katherine Bever
Marina Baretti
Mark Yarchoan
Robert A. Anders
Luciane T. Kagohara
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Daniel Laheru
Amy M. Thomas
Jennifer Durham
Julie M. Nauroth
Jiayun Lu
Hao Wang
Division of Quantitative Sciences, Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA
Elana J. Fertig
Institute for Genome Sciences, University of Maryland School of Medicine
Won Jin Ho
Nilofer S. Azad
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore
Elizabeth M. Jaffee
Neeha Zaidi