Phase I Trial of a Modified Vaccinia Ankara Priming Vaccine Followed by a Fowlpox Virus Boosting Vaccine Modified to Express Brachyury and Costimulatory Molecules in Advanced Solid Tumors.

Abstract

LESSONS LEARNED:

Modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury followed by fowlpox virus-BN-Brachyury was well tolerated upon administration to patients with advanced cancer. Sixty-three percent of patients developed CD4+ and/or CD8+ T-cell responses to brachyury after vaccination. BN-Brachyury vaccine also induced T-cell responses against CEA and MUC1, which are cascade antigens, that is, antigens not encoded in the vaccines.

BACKGROUND:

Brachyury, a transcription factor, plays an integral role in the epithelial-mesenchymal transition, metastasis, and tumor resistance to chemotherapy. It is expressed in many tumor types, and rarely in normal tissues, making it an ideal immunologic target. Bavarian Nordic (BN)-Brachyury consists of vaccination with modified vaccinia Ankara (MVA) priming followed by fowlpox virus (FPV) boosting, each encoding transgenes for brachyury and costimulatory molecules.

METHODS:

Patients with metastatic solid tumors were treated with two monthly doses of MVA-brachyury s.c., 8 × 108 infectious units (IU), followed by FPV-brachyury s.c., 1 × 109 IU, for six monthly doses and then every 3 months for up to 2 years. The primary objective was to determine safety and tolerability.

RESULTS:

Eleven patients were enrolled from March 2018 to July 2018 (one patient was nonevaluable). No dose-limiting toxicities were observed. The most common treatment-related adverse event was grade 1/2 injection-site reaction observed in all patients. Best overall response was stable disease in six patients, and the 6-month progression-free survival rate was 50%. T cells against brachyury and cascade antigens CEA and MUC1 were detected in the majority of patients.

CONCLUSION:

BN-Brachyury vaccine is well tolerated and induces immune responses to brachyury and cascade antigens and demonstrates some evidence of clinical benefit.

• Authors: Julie M Collins, Renee N Donahue, Yo-Ting Tsai, Michell Manu, Claudia Palena, Margaret E Gatti-Mays, Jennifer L Marté, Ravi A Madan, Fatima Karzai, Christopher R Heery, Julius Strauss, Houssein Abdul-Sater, Lisa Cordes, Jeffrey Schlom, James L Gulley, Marijo Bilusic
• Journal: The oncologist (Oncologist) Vol. 25 Issue 7 Pg. 560-e1006 (07 2020) ISSN: 1549-490X [Electronic] England
• PMID: 31876334 (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

• Fetal Proteins
• T-Box Domain Proteins
• Brachyury protein

Topics

• Animals
• Fetal Proteins
• Fowlpox virus
• Humans
• Neoplasms (therapy)
• T-Box Domain Proteins (genetics)
• Vaccinia
• Vaccinia virus (genetics)