Clinical Trials

Date: 2017-01-04

Type of information: DSMB assessment

phase: 3

Announcement: update

Company: Bavarian Nordic (Denmark)

Product: Prostvac® (rilimogene)

Action mechanism:

• immunotherapy product/gene therapy. Prostvac® is a PSA-targeted, ready-to-use active immunotherapy for the treatment of prostate cancer. Prostvac® is being developed in collaboration with the National Cancer Institute under a Cooperative Research and Development Agreement. In April 2010, Prostvac® was granted Fast Track designation by the FDA for the treatment of men with asymptomatic or minimally symptomatic mCRPC.

Disease: asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)

Therapeutic area: Cancer - Oncology

Country: Australia, Belgium, Canada, Denmark, Estonia, France, Germany, Iceland, Israel, The Netherlands, Poland, Puerto Rico, Russian Federation, Spain, UK, USA

Trial details:

• The PROSPECT study is a global randomized, double-blind, placebo-controlled study in patients with asymptomatic or minimally symptomatic mCRPC.  It is a 3-arm study and will evaluate overall survival in two separate comparisons, Prostvac® plus adjuvant dose GM-CSF versus controls, and PROSTVAC without GM-CSF versus controls. (NCT01322490)

Latest news:

• • On September 14, 2017, Bavarian Nordic announced that an independent Data Monitoring Committee (DMCB) has determined, based on a preplanned interim analysis, that continuation of the Phase 3 PROSPECT study of Prostvac® in patients with metastatic castration-resistant prostate cancer (mCRPC) is futile. The study enrolled 1,297 patients at more than 200 sites in 15 countries.
• • On January 4, 2017, Bavarian Nordic provided guidance for the current estimated timing of interim and final overall survival analysis from the PROSPECT study - a placebo controlled Phase 3 study designed to investigate the efficacy of Prostvac® to prolong the survival of men with metastatic castration-resistant prostate cancer (mCRPC). The company maintains its previous guidance that full data is expected within this year, albeit in the second half of 2017, with the third interim analysis likely to occur around mid-2017. This estimate is based on a decline in the number of average monthly events currently seen in the PROSPECT study. While the company remains blinded to all patient specific data, the latest estimates have been provided by the independent Data Monitoring Committee (DMC) following a routine analysis of the current survival data. The objective of the study is to determine whether Prostvac® alone or in combination with GM-CSF is effective in prolonging overall survival. The study has been fully enrolled with 1,297 asymptomatic or minimally symptomatic mCRPC patients as of January 2015. Patients were enrolled at more than 200 sites in 15 countries. Both the first and second interim analyses confirmed that the study would continue as planned. Final study data requires 534 events in both comparisons of treatment arms versus placebo, and the third interim analysis will occur at 427 events. The first interim analysis took place in February 2016 based upon the occurrence of 214 events, and the second interim analysis took place in July 2016 based upon the occurrence of 321 events. Both analyses confirmed that the study will continue as planned. While the final study data are anticipated in 2017 and requires 534 events in both comparisons, a third interim analysis will occur at 427 events. Should the PROSPECT trial prove successful, applications for approval will be made in the United States, the European Union and other territories.
• • On December 10, 2014, Bavarian Nordic announced that it has reached the planned enrollment of 1,200 patients in the PROSPECT Phase 3 clinical study of its targeted active immunotherapy candidate, Prostvac®, in the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Patients were enrolled at 214 sites in 15 countries. The PROSPECT Phase 3 global study is being executed under the leadership of principal investigators James L. Gulley, M.D., Ph.D., Chief Genitourinary Malignancies Branch, Head, Immunotherapy Section, Center for Cancer Research, National Cancer Institute and Phil Kantoff, MD., Chief, Division of Solid Tumor Oncology, Director, Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. The trial is being conducted under a Special Protocol Assessment agreement with the FDA. The primary objective of the study is to determine whether the overall survival of patients receiving PROSTVAC (with or without the addition of granulocyte macrophage colony-stimulating factor; GM-CSF), is superior to that of patients receiving placebo. The final analysis of the study will occur when 534 deaths have occurred in either one or both comparisons of the treatment arms vs. placebo. Integrated in the statistical plan are pre-specified interim analyses of data which will evaluate whether the trial should continue as planned or potentially be stopped early for efficacy. In such case, a Biologics License Application may be filed at an earlier stage, potentially shortening the overall development.
• • On April 8, 2013, Bavarian Nordic has announced that the Company plans to conduct an interim analysis of the on-going PROSPECT Phase 3 trial of Prostvac® in prostate cancer patients with metastatic disease. The updated statistical analysis plan for the trial, which was recently accepted by the FDA, now includes pre-specified interim analyses of data that will be performed to evaluate whether the trial should continue as planned or potentially be stopped early for efficacy. In such case, a Biologics License Application may be filed at an earlier stage, potentially shortening the overall development time. Enrollment in the trial is currently ongoing at almost 100 sites in 10 countries, and continues to expand into new countries and sites. As previously communicated, the initiation of new sites has been delayed due to a lengthier and more arduous regulatory process than anticipated in certain countries. Bavarian Nordic has responded to this delay by implementing a number of measures, aimed at completing enrollment within approximately one year. Two abstracts have been accepted for the American Society of Clinical Oncology (ASCO) Annual Meeting on May 31-June 4, 2013 in Chicago, Illinois, covering clinical safety data for Prostvac®, and the rationale for and design of two new studies of Prostvac® given in combination with enzalutamide.
• • On November 15, 2011, Bavarian Nordic has announced that its subsidiary, BN ImmunoTherapeutics has initiated the pivotal Phase 3 trial of Prostvac® for patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. The trial is being conducted under a Special Protocol Assessment agreement with the FDA.

Is general: Yes