FDA Recommends Termination of Phase 2 Trial Examining Immunotherapy ERC1671 in Glioblastoma

The FDA has recommended the early termination of a phase 2 trial (NCT01903330) examining the cell-based immunotherapy ERC1671 (Gliovac or Sitoiganap) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), cyclophosphamide, and bevacizumab (Avastin) in patients with glioblastoma, according to an announcement from Epitopoietic Research Corporation (ERC)–USA and the University of California, Irvine.¹

In place of this trial, the regulatory agency recommends that a phase 3 registrational trial be conducted. The data from this trial could potentially be used to support the filing of a new drug application (NDA) for the regimen to obtain future FDA approval for use in this population.

“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,” Daniela A. Bota, MD, PhD, vice dean for Clinical Research and medical director of Comprehensive Brain Tumor Program at the University of California, Irvine School of Medicine, stated in a press release.

The advanced immunotherapy, ERC1671, is based on freshly extracted tumor cells and lysates that rouses the immune system to identify and reject cancer cells. The agent comprises autologous and allogeneic tumor cells that are produced from the glioma tumor tissues of 3 donor patients with cancer, as well as the lysates of all these cells. Once injected, the product stimulates the immune system to induce a response against tumor cells to eliminate them.

In the blinded phase 2 trial, investigators evaluated the efficacy of ERC1671 plus GM-CSF, cyclophosphamide, and bevacizumab vs placebo/bevacizumab in the treatment of patients with recurrent or progressive, bevacizumab-naïve glioblastoma multiforme and gliosarcoma.² 

To be eligible for enrollment, patients had to be at least 18 years of age, have a histologic diagnosis of glioblastoma or gliosarcoma, a Karnofsky performance score of 70% or greater, and a life expectancy of more than 12 weeks. Patients needed to have been in their first or second relapse and they must have previously undergone surgery, underwent conventional radiation treatment, and received temozolomide.

Patients who have diffuse leptomeningeal disease; a history, presence, or suspicion of metastatic disease; received immunosuppressive agents less than 2 weeks before first dose of ERC1671; or who previously received bevacizumab, bevacizumab biosimilars, or other anti-VEGF agents, were excluded.

ERC1671/GM-CSF were administered intradermally, while cyclophosphamide was given orally. Patients received GM-CSF at a fixed dose of 500 mcg, while they received a 50 mg/day dose of cyclophosphamide. Bevacizumab, or approved bevacizumab biosimilars, were given at a dose of 10 mg/kg every 2 weeks. Treatment was given in 28-day cycles until either disease progression or unacceptable toxicity.

The primary end point of the trial was overall survival (OS) at 12 months, while secondary end points included progression-free survival, immune response, toxicity, and rate of radiographic response per MacDonald Criteria or iRANO criteria.

Interim data from the trial, reported in August 2020, showed that the 6-month OS rate in the first 10 patients who received ERC1671 was 100%; the 12-month OS rate was 40%. Additionally, the median OS with the regimen was 10.5 months.³ In comparison, historic controls had a 6-month OS rate of just 33% and a median OS of just 5.3 months. The improvement in OS benefit with ERC1671 proved to be highly significant (log rank test, P <.0001).

Additionally, about 10% of patients who were given ERC1671 experienced total recovery and survived longer than 3 years after glioblastoma recurrence and having received standard-of-care treatment. No spontaneous remissions were noted in the control arm of the trial; all of these patients experienced disease progression.

A subgroup of patients who had progressed on treatment with bevacizumab were found to disproportionately benefit from ERC1671, with a doubling in survival benefit vs historical controls.

“We are thrilled that the FDA now recognizes the potential of ERC1671 to treat this intractable disease and major unmet medical need,” Apostolos Stathopoulos, MD, PhD, president and chief executive officer of ERC Belgium, added in the release. “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.”

References

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. April 7, 2021. Accessed April 7, 2021. https://bit.ly/39Q6Q67
2. ERC1671/GM-CSF/cyclophosphamide for the treatment of glioblastoma multiforme. ClinicalTrials.gov. Updated February 23, 2021. Accessed April 7, 2021. https://clinicaltrials.gov/ct2/show/NCT01903330
3. 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. https://bwnews.pr/39Rf6mg