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PROSTVAC

Prostate cancer immunotherapy candidate

PHASE 3


PROSTVAC is Bavarian Nordic’s lead targeted immunotherapy candidate that is being investigated for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Encouraging results from the PROSTVAC development program are being validated with the ongoing pivotal phase 3 PROSPECT study, conducted in collaboration with the National Cancer Institute under a Special Protocol Assessment from the U.S. Food and Drug Administration (FDA). Data to date also suggest that PROSTVAC has potential in combination with other therapies and/or in earlier stages of the disease.

Tumor volume and activity

Prostate Cancer
No pain Pain
Hormone dependent Castration resistant
Nonmetastatic Metastatic

Figure courtesy of William K. Oh, MD; ASCO 2011.

PROSTVAC is being studied to see if it has the potential to extend the lives of men with mCRPC, who have limited treatment options. The hypothesis behind a targeted immunotherapy with a potentially favorable safety profile is that it may do so with less of an impact on quality of life. PROSTVAC employs the company’s prime/boost technology platform and targets prostate-specific antigen (PSA), and is believed to induce a specific, direct immune response that attacks prostate cancer.

PROSTVAC is administered subcutaneously, which may provide ease of use for physicians and patients.

PROSTVAC immunotherapy is intended to trigger a specific and targeted immune response against prostate cancer cells and tissue by using virus-based immunotherapies that carry the tumor-associated antigen PSA (prostate-specific antigen) along with 3 natural human immune-enhancing costimulatory molecules collectively designated as TRICOM (LFA-3, ICAM-1, and B7.1).

  • When PSA-TRICOM is presented to the immune system in the PROSTVAC regimen, cytotoxic T lymphocytes (CTLs) are generated that may recognize and kill PSA-expressing cancer cells
  • A cascade effect may also occur, which may overcome the immunosuppressive cancer microenvironment and lead to immune recognition of other tumor-associated antigens

PROSTVAC is being developed in partnership with the National Cancer Institute under a formal Collaborative Research and Development Agreement and has been the subject of 8 completed and 10 ongoing clinical studies. Encouraging results from these clinical studies, specifically the randomized, double-blind, placebo-controlled phase 2 study (see below), have formed the scientific and clinical basis for the phase 3 PROSPECT pivotal study currently ongoing.

16 ongoing or completed PROSTVAC clinical studies

  Completed Ongoing
Phase 1 4 -
Phase 2 4 9
Phase 3 - 1
Total 8 10
Total patients 300+ 1,800+


PROSTVAC was tested in 2 phase 1 studies and a single-arm phase 2 study prior to the initiation of a randomized, controlled, double-blind phase 2 clinical study that enrolled 125 minimally symptomatic mCRPC patients across 43 centers in the United States. Patients who received PROSTVAC had a median overall survival that was 8.5 months longer than the control group (25.1 vs 16.6 months) and a 44% reduction in the risk of death (stratified log-rank P=.0061). PROSTVAC was generally well tolerated, with the most common side effects including injection site reactions, fever, fatigue, and nausea.


PROSTVAC Phase 2 Results

Potentially Promising Increase in Survival in mCRPC

PROSTVAC Overall Survival

  Arm N Deaths Median OS (months)
PROSTVAC 82 65 25.1
Control 40 37 16.6
 

8.5 months improvement in OS
Hazard ratio = 0.56 (95% CI 0.37-0.85), P=.0061

The PROSTVAC regimen consists of an initial PSA-TRICOM vaccinia-based priming dose, followed by 6 subsequent PSA-TRICOM fowlpox-based boosting doses. These 7 subcutaneous injections are given within a 5-month treatment period.

Priming Dose*
(Vaccinia-based)
Boosting doses*
(Fowlpox-based)
Wk1 Wk3 Wk5 Wk9 Wk13 Wk17 Wk21

*Or matching placebo.
Adjuvant low-dose granulocyte-macrophage colony-stimulating factor (GM-CSF, 100 µg) or placebo given subcutaneously on days 1- 4 for each PROSTVAC dose.