Battling brachyury

Phase 1 study indicates safety and efficacy of Bavarian Nordic vaccine in advanced cancer patients

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COPENHAGEN, Denmark—Advanced cancer patients can be safely immunized with an modified vaccinia virus Ankara (MVA)-based vaccine targeting brachyury, and they can develop brachyury-specific T cell immune responses, according to a poster presentation at the Society for Immunotherapy of Cancer’s Annual Meeting in National Harbor, Md., titled “Phase 1, dose escalation, clinical trial of MVA-Brachyury-TRICOM Vaccine demonstrating safety and brachyury-specific T cell responses.” The poster summarizes the results of Bavarian Nordic’s NCI-sponsored Phase 1 study investigating the company’s cancer vaccine, MVA-BN Brachyury.
Brachyury, a tumor-associated antigen and transcription factor that drives the epithelial-to-mesenchymal transition in human carcinomas, reportedly plays a key role in tumor metastasis and progression. It is especially prevalent in several kinds of lung cancer, making it a logical target for determining a therapeutic route. This Phase 1 dose escalation study assessed whether patients with advanced cancer or chordoma, a rare tumor of the notochord that overexpresses brachyury, can elicit brachyury-specific T cell responses following vaccination with MVA-Brachyury-TRICOM.
Bavarian Nordic, an integrated biotechnology company, is focused on the development, manufacturing and commercialization of cancer immunotherapies and vaccines for infectious diseases based on its live virus vaccine platform. The company has developed a portfolio of vaccines for infectious diseases, including the non-replicating smallpox vaccine, IMVAMUNE. Bavarian Nordic and its partner, Janssen, are developing an Ebola vaccine regimen. In collaboration with the U.S. National Cancer Institute (NCI), Bavarian Nordic has developed a portfolio of active cancer immunotherapies, including PROSTVAC, which is currently in Phase 3 clinical development for the treatment of advanced prostate cancer.
The company developed MVA-BN Brachyury using the MVA-BN (Modified Vaccinia Ankara Bavarian Nordic) platform. The clinical study has shown that MVA-BN is well tolerated and induces a strong immune response in advanced cancer patients, according to the company.
Dr. Christopher R. Heery, director of the Clinical Trials Group in the Laboratory of Tumor Immunology and Biology of the Center for Cancer Research at NCI, was the study’s principal investigator. The study enrolled 13 patients with chordoma and 25 patients with other metastatic, solid cancers. Patients were enrolled in groups of three, receiving escalating doses of MVA-BN Brachyury in three cycles, every four weeks. Once safety was established, additional patients were enrolled at the two highest doses.
According to the researchers, MVA-BN Brachyury was well tolerated with no dose-limiting toxicities.
The maximal tolerated dose was not reached, and no serious adverse vaccine-related events were observed. Immune responses were analyzed in 29 patients. Brachyury-specific T cell responses were observed at each dose level: 66 percent of patients at dose level one, 80 percent at dose level two and 90 percent at dose level three. At the two highest dose levels, about 80 percent of the patients who developed brachyury-specific T cells demonstrated responses in both CD4 and CD8 T-lymphocytes.
Paul Chaplin, president and CEO of Bavarian Nordic, described the Phase 1 study as “very positive news on many levels.” As he explained, “We now have confirmation that an MVA-BN based cancer immunotherapy can elicit a T cell response against a specific tumor target. Additionally, finding a therapeutic approach to treating brachyury expression, which is not normally found on a tumor cell surface, has to date proven to be quite difficult. The creation of a vaccine-based, immunotherapy approach could be a unique solution to targeting a tumor antigen which has been associated with high rates of metastasis and multidrug resistance.”
Heery concluded, “These findings show for the first time that advanced cancer patients can be safely immunized with an MVA-based vaccine targeting brachyury, and can develop brachyury-specific T cell immune responses. These results warrant further studies using this vaccine in additional cohorts of cancer patients.”
The same day Bavarian Nordic announced the news of this Phase 1 trial, it also published its interim financial report for the first nine months of 2015. Financial expectations for the full year were maintained. As for some of the other highlights of the report that were focused mostly on the third quarter of the fiscal year:
  • In July, Bavarian Nordic received a new order from the U.S. government for bulk supply of IMVAMUNE smallpox vaccine valued at $133 million.
  • In July, an NCI-sponsored Phase 2 study of PROSTVAC in up to 150 patients with localized prostate cancer was initiated.
  • In August, the first-in-human Phase 1 study investigating a new MVA-BN based vaccine against respiratory syncytial virus was initiated, and the 63-patient study is now fully enrolled.
  • In September, Bavarian Nordic was awarded a subcontract valued at up to $33 million from Janssen as part of a contract to support the advanced development and manufacturing of the MVA-BN/AdVac prime-boost Ebola vaccine regimen.
  • In October, a safety and immunogenicity study of the prime-boost Ebola vaccine regimen was initiated in Sierra Leone.
  • In October, Bavarian Nordic received a new order from Canada for IMVAMUNE valued at $6.4 million.
Chaplin said, “Significant progress has been made in our pipeline during the year. In particular, the accelerated advancement of our Ebola vaccine regimen into Phase 3 trials was a major accomplishment. In addition, the initiation of clinical development of our RSV vaccine marks an important entry into new, commercially attractive markets. Additional pipeline progress is planned in the near term, notably with CV-301 immunotherapy, beginning with lung cancer and in multiple cancers thereafter. We are also very pleased with the continued support from the U.S. government for the procurement of IMVAMUNE, highlighting our large-scale vaccine manufacturing expertise.”

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