Date: 2016-03-07
Type of information: discontinuation of development
phase: 3
Announcement: discontinuation of the trial
Company: Celldex Therapeutics (USA - NJ)
Product: Rintega® (rindopepimut)
Action
mechanism: Rindopepimut (Rintega®) is an investigational immunotherapy that targets the tumor specific oncogene EGFRvIII (v3), a functional and permanently activated variant of the epidermal growth factor receptor (EGFR). Expression of EGFRvIII correlates with increased tumorigenicity in mouse models and poor long term survival in clinical studies of patients with glioblastoma. In addition, EGFRvIII-positive cells are believed to stimulate proliferation of non-EGFRvIII cells through IL-6 cell-to-cell signaling and to release microvesicles containing EGFRvIII, which can merge with neighboring cells, transferring tumor-promoting activity. EGFRvIII expression may also be associated with tumor stem cells that have been identified in glioblastoma. These stem cells contribute to resistance to cytotoxic therapy and tumor recurrence. EGFRvIII is expressed in tumors in about 30% of patients with glioblastoma. It has not been detected at a significant level in normal tissues; therefore, targeting of this tumor-specific molecule is not likely to impact healthy tissues. Rindopepimut has received Fast Track Designation in the United States and Orphan Drug Designation in both the United States and the European Union.
Disease: EGFRvIII positive glioblastoma
Therapeutic area: Cancer - Oncology - Rare diseases
Country: Australia, Austria,Belgium, Brazil, Canada, Colombia, Czech Republic, France, Germany, Greece, Hungary, India, Israel, Italy, Mexico Netherlands,New Zealand,Peru,Spain,Switzerland,Taiwan,Thailand,United Kingdom, USA
Trial
details: The ACT IV study is a randomized, double-blind, placebo controlled study of rindopepimut plus GM-CSF added to standard of care temozolomide in patients with newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma. In total, over 4,800 patients were screened for EGFRvIII status from more than 200 clinical trial sites across 22 countries and, consistent with prior studies, 30% were positive for the EGFRvIII mutation. 745 patients were enrolled into ACT IV to reach the required 374 patients with minimal residual disease (assessed by central review) needed for analysis of the primary overall survival endpoint. All patients, including patients with disease that exceed this threshold, will be included in a secondary analysis of overall survival as well as analyses of progression-free survival, safety and tolerability, and quality of life. (NCT01480479)
Latest
news: * On March 7, 2016, Celldex Therapeutics announced that the independent Data Safety and Monitoring Board (DSMB) has determined, based on a preplanned interim analysis, that continuation of the Phase 3 ACT IV study of Rintega® (rindopepimut) in patients with newly diagnosed EGFRvIII-positive glioblastoma will not reach statistical significance for overall survival in patients with minimal residual disease, the primary endpoint of the study, as both the Rintega® arm and the control arm are performing on par with each other. In the ACT IV study, Rintega® has performed consistently with prior Phase 2 studies but the control arm has significantly outperformed expectations (Hazard ratio = 0.99; median OS: Rintega® 20.4 months vs. control 21.1 months). Based on this recommendation, Celldex is discontinuing the study and does not anticipate incurring substantial additional costs related to Rintega® at this time. All patients on the Rintega® arm of the ACT IV study, prior Phase 2 studies and existing compassionate use recipients will be offered ongoing access to Rintega® on a compassionate use basis. Celldex currently has seven company-led clinical trials across five product candidates ongoing. The Company expects to report data from a number of these studies over the next three to 18 months, including a registration study in triple negative breast cancer and a number of Phase 1 and 2 cancer immunotherapy combination trials. * On December 15, 2014, Celldex Therapeutics announced that patient enrollment has been completed in the Company's Phase 3 ACT IV study of rindopepimut in EGFRvIII positive glioblastoma. Interim analyses will be conducted by an independent Data Safety and Monitoring Board at 50 and 75% of events. The first interim analysis is expected in mid-2015 and will provide insight into the frequency of events to inform estimates regarding timing for the second interim and final data read out.
