A Phase I Trial Using a Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury)-Based Immunotherapy Vaccine Regimen in Patients with Advanced Cancer.

Abstract

LESSONS LEARNED:

Concurrent ETBX-011, ETBX-051, and ETBX-061 can be safely administered to patients with advanced cancer. All patients developed CD4+ and/or CD8+ T-cell responses after vaccination to at least one tumor-associated antigen (TAA) encoded by the vaccine; 5/6 patients (83%) developed MUC1-specific T cells, 4/6 (67%) developed CEA-specific T cells, and 3/6 (50%) developed brachyury-specific T cells. The presence of adenovirus 5-neutralizing antibodies did not prevent the generation of TAA-specific T cells.

BACKGROUND:

A novel adenovirus-based vaccine targeting three human tumor-associated antigens-CEA, MUC1, and brachyury-has demonstrated antitumor cytolytic T-cell responses in preclinical animal models of cancer.

METHODS:

This open-label, phase I trial evaluated concurrent administration of three therapeutic vaccines (ETBX-011 = CEA, ETBX-061 = MUC1 and ETBX-051 = brachyury). All three vaccines used the same modified adenovirus 5 (Ad5) vector backbone and were administered at a single dose level (DL) of 5 × 1011 viral particles (VP) per vector. The vaccine regimen consisting of all three vaccines was given every 3 weeks for three doses then every 8 weeks for up to 1 year. Clinical and immune responses were evaluated.

RESULTS:

Ten patients enrolled on trial (DL1 = 6 with 4 in the DL1 expansion cohort). All treatment-related adverse events were temporary, self-limiting, grade 1/2 and included injection site reactions and flu-like symptoms. Antigen-specific T cells to MUC1, CEA, and/or brachyury were generated in all patients. There was no evidence of antigenic competition. The administration of the vaccine regimen produced stable disease as the best clinical response.

CONCLUSION:

Concurrent ETBX-011, ETBX-051, and ETBX-061 can be safely administered to patients with advanced cancer. Further studies of the vaccine regimen in combination with other agents, including immune checkpoint blockade, are planned.

• Authors: Margaret E Gatti-Mays, Jason M Redman, Renee N Donahue, Claudia Palena, Ravi A Madan, Fatima Karzai, Marijo Bilusic, Houssein Abdul Sater, Jennifer L Marté, Lisa M Cordes, Sheri McMahon, Seth M Steinberg, Alanvin Orpia, Andrea Burmeister, Jeffrey Schlom, James L Gulley, Julius Strauss
• Journal: The oncologist (Oncologist) Vol. 25 Issue 6 Pg. 479-e899 (06 2020) ISSN: 1549-490X [Electronic] England
• PMID: 31594913 (Publication Type: Clinical Trial, Phase I, Journal Article)
• Copyright: © AlphaMed Press; the data published online to support this summary are the property of the authors.

Chemical References

• Cancer Vaccines
• Carcinoembryonic Antigen
• Fetal Proteins
• MUC1 protein, human
• Mucin-1
• T-Box Domain Proteins
• Brachyury protein

Topics

• Adenoviridae (genetics)
• Animals
• Cancer Vaccines
• Carcinoembryonic Antigen
• Fetal Proteins
• Humans
• Immunotherapy
• Mucin-1
• Neoplasms (therapy)
• T-Box Domain Proteins