The FDA has issued a letter to the developer of the immunotherapy vaccine, ERC1671, recommending that the phase 2 clinical trial of ERC1671 in combination with granulocyte-macrophage colony-stimulating factor, and cyclophosphamide for the treatment of glioblastoma be terminated.
The FDA has issued a letter to the developer of the immunotherapy vaccine, ERC1671, recommending that the phase 2 clinical trial of ERC1671 in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), and cyclophosphamide for the treatment of glioblastoma be terminated, according to a press release from ERC-USA and the University of California, Irvine.1
In place of the current study, the FDA recommends that ERC-USA conduct a phase 3 confirmatory study, from which data could support the future filing of a Biologics License Application and potentially lead to an FDA approval.
“We are highly reassured that the FDA shares our view that ERC1671 should enter a registration trial and move toward an NDA as soon as possible,” said Daniela A. Bota, MD, PhD, vice dean for Clinical Research, University of California, Irvine School of Medicine, and medical Director, UCI Health Comprehensive Brain Tumor Program and principal investigator of the phase 2 study, in the press release.
The cell-based immunotherapy ERC1671 was showing promise as treatment of recurrent glioblastoma based on interim results from the phase 2 study. A total of 10 patients were included in the first analysis and a 6-month overall survival rate of 100% was achieved as a well as a 12-month OS rate of 40% with the combination of ERC1671, GM-CSF, and cyclophosphamide. The median OS observed with the combination in the study was 10.5 months. It was noted in a 2020 press release that the interim results were better than historic controls which showed a 6-month OS rate of only 33% and a median OS of only 5.3 months (P < .0001).2
The trial was double-blinded and placebo-controlled. 84 patients were randomized 1:1in the study receive either ERC1671 plus GM-CSF and cyclophosphamide or placebo plus bevacizumab (Avastin). The secondary end points explored were progression-free survival rate, immune response, the percentage of grade 3 through 5 adverse events, and the rate of radiographic response.
Patients were eligible to enroll if they were at least 18 years of age with a histologic diagnosis of glioblastoma or gliosarcoma, a Karnofsky Performance score ≥ 70%, a life expectancy of at least 12 weeks, measurable disease, adequate organ function, and who are in their first or second relapse of glioblastoma. In terms of prior treatment, patients were eligible for the study given they had prior surgery for glioblastoma and systemic corticosteroid therapy of ≤ 4 mg of dexamethasone or equivalent.
Individuals who were unable to undergo an MRI with contrast were excluded from the study along with those who had the presence of diffuse leptomeningeal disease, history, presence, or risk of metastatic disease, significant vascular disease, and other conditions that may have interfered with on-study treatment. In addition, the study excluded those who received immunosuppressive drugs less than 2 weeks before the first dose of ERC1671, bevacizumab, bevacizumab biosimilars, other VEGF-targeted agents, and those with hypersensitivity to bevacizumab.
Following the early success of ERC1671, ERC-USA considers the response from the FDA to be helpful for the future development of the agent, which may fill a treatment gap for patients with recurrent glioblastoma who currently have no effective treatment options.
“We are thrilled that the FDA now recognizes the potential of ERC1671 to treat this intractable disease and major unmet medical need. We believe ERC1671 provides significant hope to patients with recurrent glioblastoma and we are grateful to the FDA’s encouragement to aggressively enter into a registration trial, said Apostolos Stathopoulos, MD, PhD, president and chief executive office of ERC Belgium, parent company to ERC-USA, in a statement.
1. ERC-USA announces FDA recommendation for early termination of phase 2 clinical trial of ERC1671 (Gliovac or Sitoiganap) and application for registration trial for treatment of glioblastoma. News release. ERC-USA. April 7, 2021. Accessed April 7, 2021.
2. ERC announces interim results from phase 2 trial of immunotherapy ERC1671 in recurrent glioblastoma patients. News release. ERC Belgium. August 19, 2020. Accessed April 7, 2021.