A phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma

Tira J. Tan, W. X. Gladys Ang, Who-Whong Wang, Hui-Shan Chong, Sze Huey Tan, Rachael Cheong, John Whay-Kuang Chia, Nicholas L. Syn, Wai Ho Shuen, Rebecca Ba, Nivashini Kaliaperumal, Bijin Au, Richard Hopkins, Xinhua Li, Aaron C. Tan, Amanda O. L. Seet, John E. Connolly, Thaschawee Arkachaisri, Valerie Chew, Ahmad bin Mohamed Lajam, Dianyan Guo, Marvin Z. W. Chew, Martin Wasser, Pavanish Kumar, Salvatore Albani () and Han Chong Toh ()
Additional contact information
Tira J. Tan: National Cancer Centre
W. X. Gladys Ang: SingHealth Duke-NUS Academic Medical Centre
Who-Whong Wang: National Cancer Centre
Hui-Shan Chong: National Cancer Centre
Sze Huey Tan: National Cancer Centre
Rachael Cheong: National Cancer Centre
John Whay-Kuang Chia: Curie Oncology
Nicholas L. Syn: National University of Singapore
Wai Ho Shuen: National Cancer Centre
Rebecca Ba: National Cancer Centre
Nivashini Kaliaperumal: Agency for Science, Technology and Research (A*STAR)
Bijin Au: Agency for Science, Technology and Research (A*STAR)
Richard Hopkins: Agency for Science, Technology and Research (A*STAR)
Xinhua Li: Singapore Clinical Research Institute (SCRI)
Aaron C. Tan: National Cancer Centre
Amanda O. L. Seet: National Cancer Centre
John E. Connolly: Agency for Science, Technology and Research (A*STAR)
Thaschawee Arkachaisri: Rheumatology and Immunology Service, KK Women’s and Children’s Hospital
Valerie Chew: SingHealth Duke-NUS Academic Medical Centre
Ahmad bin Mohamed Lajam: SingHealth Duke-NUS Academic Medical Centre
Dianyan Guo: SingHealth Duke-NUS Academic Medical Centre
Marvin Z. W. Chew: SingHealth Duke-NUS Academic Medical Centre
Martin Wasser: SingHealth Duke-NUS Academic Medical Centre
Pavanish Kumar: SingHealth Duke-NUS Academic Medical Centre
Salvatore Albani: SingHealth Duke-NUS Academic Medical Centre
Han Chong Toh: National Cancer Centre

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Cancer vaccines as immunotherapy for solid tumours are currently in development with promising results. We report a phase 1 study of Ad-sig-hMUC1/ecdCD40L (NCT02140996), an adenoviral-vector vaccine encoding the tumour-associated antigen MUC1 linked to CD40 ligand, in patients with advanced adenocarcinoma. The primary objective of this study is safety and tolerability. We also study the immunome in vaccinated patients as a secondary outcome. This trial, while not designed to determine clinical efficacy, reports an exploratory endpoint of overall response rate. The study meets its pre-specified primary endpoint demonstrating safety and tolerability in a cohort of 21 patients with advanced adenocarcinomas (breast, lung and ovary). The maximal dose of the vaccine is 1 ×1011 viral particles, with no dose limiting toxicities. All drug related adverse events are of low grades, most commonly injection site reactions in 15 (71%) patients. Using exploratory high-dimensional analyses, we find both quantitative and relational changes in the cancer immunome after vaccination. Our data highlights the utility of high-dimensional analyses in understanding and predicting effective immunotherapy, underscoring the importance of immune competency in cancer prognosis.

Date: 2022
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DOI: 10.1038/s41467-022-33834-4

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