Phase 2 Study Will Evaluate VBI-1901 and Balstilimab Combination for the Treatment of Glioblastoma

October 13, 2022

Article

As part of the phase 2 INSIGhT trial, VBI Vaccines, Inc, and Agenus will examine the combination of VBI-1901 and balstilimab in patients with glioblastoma.

About the Phase 2 INSIGhT Trial

Trial Name: INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)

ClinicalTrials.gov Identifier: NCT02977780

Sponsor: Patrick Y. Wen, MD

Completion Date: December 2024

A collaboration between VBI Vaccines, Inc. and Agenus will evaluate the combination of VBI-1901, a monoclonal antibody targeting the PD-1 protein, and balstilimab in patients with primary glioblastoma as part of the adaptive INSIGhT trial (NCT02977780).¹

The agreement states that VBI Vaccines, Inc, will be the sponsor of the study and responsible for operational execution of the combination trial. Agenus will provide the supply of the study drug along with scientific support.

“Glioblastomas are notoriously 1 of the most immunosuppressive solid tumors, which is why there are few effective treatment options. Based upon the encouraging data we have observed to date, we believe VBI-1901 has the potential to activate and boost specific T-cell immunity capable of trafficking to the tumor microenvironment, stated David E. Anderson, PhD, chief scientific officer of VBI Vaccines, Inc, in the press release. “We are now adding an anti-PD-1 monoclonal antibody to the treatment regimen as it may help to further enhance and sustain a meaningful anti-tumor immune response. An anti-PD-1 is designed to prolong the life of these T cells so that they may have greater opportunity to infiltrate and kill tumor cells. Given this potential synergy, we are excited to be partnering with Agenus in this clinical collaboration.”

INSIGhT is a phase 2 trial aiming to compare the effects of the standard of care treatment for patients with glioblastoma with 3 investigational agents, abemaciclib (Verzenio), neratinib (Nerlynx), and CC-115.²

In the active comparator arm, temozolomide (Temodal) will be administered orally on a daily dosing schedule approximately 2-3 hours before each session of radiotherapy and post radiation for up to 6 cycles. Then, the first experimental arm will be given temozolomide orally on a daily dosing schedule 2-3 hours before each session of radiotherapy followed by neratinib, which will be taken post-radiation at a daily oral pre-determined dose. The other experimental arm will administer QBS10072S on day 1 of radiation treatment as well as post-radiation for up to 6 cycles.

Enrollment is open to patients aged 18 years and older with a histologically confirmed diagnosis of intracranial glioblastoma or gliosarcoma following maximum surgical resection. Those who have had prior surgery for glioblastoma or gliosarcoma but no systemic or radiation therapy are eligible for enrollment. Patients must also have a Karnofsky performance status ≥60, normal organ and marrow function, the ability to swallow pills, plan to begin radiation therapy 14-42 days after surgical resection, immunohistochemically negative for IDH1 R132H mutation, and the evidence that the tumor MGMT promoter is unmethylated by standard of care assays.

The primary end point of the trial is OS (overall survival) and the secondary end points are incidence of treatment-emergent adverse events, progression-free survival (PFS), OS, and the association between PFS and OS effects of experimental agents.

Currently, VBI-1901 is also being examined in a 3-part, dose-escalation, phase 1/2 study (NCT03382977). The trial aims to determine the safety, tolerability, and optimal dose level of VBI-1901 with subsequent extension of optimal dose level in 38 patients with recurrent glioblastoma.³

Patients are eligible for enrollment if between the ages of 18 and 70 and have histologically confirmed WHO grade IV glioblastoma. Additional inclusion criteria require patients to have unequivocal evidence of tumor recurrence as assessed by an MRI of the brain, have recovered from surgery side effects and toxicity to prior therapies, and be stable or decreasing on a corticosteroid of 4 mg daily or higher for at least 5 days. Patients must also have a Karnofsky performance score of ≥ 70% and adequate organ function.

A negative pregnancy test within 14 days prior to starting VBI-1901 treatment is required for female patients, and contraception use is required throughout the study. All patients must have a tumor specimen available for central pathological review to enroll in the study.

The primary end point is to assess dose-limiting toxicities with secondary end points consisting of the immunogenicity and optimal vaccine-induced immunity-serum IgG anti-gB antibodies, cellular immunity against HCMV gB and pp65 antigens, changes in frequencies of myeloid suppressors cells and regulatory T cell, PFS, OS, median OS, decrease in steroid use compared with baseline, change in quality-of-life, and the immunogenicity of the optimal dose of VBI-1801 formulated with either granulocyte-macrophage colony-stimulating factor or AS01B adjuvants.

Early data from this study showed encouraging tumor responses and improvement in OS compared with historical controls. The arm that will be advanced into the primary setting has seen 2 patients achieve partial responses and 5 with stable disease among 16 patients with recurrent glioblastoma.

One patient who had a partial response has been on treatment protocol for over 2 and a half years along with a sustained tumor response reduction of 93% relative to baseline. Further, tumor responses have translated to clinical benefit with the median OS rate is 12.9 months. This OS rate compares favorably with the 8-month OS historical control in the recurrent setting after patients were treated with a monotherapy.

“This clinical collaboration with VBI Vaccines, Inc, is aligned with our priority of developing balstilimab as a component of novel combination therapies across a range of tumor types. Balstilimab is a promising anti-PD-1 therapy that has been studied in over 750 patients. Balstilimab has demonstrated clinically meaningful results alone and combined with anti-CTLA-4 therapy in advanced cervical cancer. Combining balstilimab with VBI’s vaccine enhances innate and adaptive anti-tumor immunity and may offer promise to patients with glioblastoma, an aggressive and difficult to treat cancer,” added Steven O’Day, MD, chief medical officer of Agenus, in the press release.

References:

1. VBI vaccines and agenus announce collaboration to evaluate VBI-1901 in combination with anti-PD-1 balstilimab in a phase 2 study in primary glioblastoma patients. News release. VBI Vaccines, Inc. Updated October 12, 2022. Accessed October 13, 2022.https://yhoo.it/3VpWeB5

2. INdividualized screening trial of innovative glioblastoma therapy (INSIGhT). ClinicalTrials.gov. Updated August 16, 2022. Accessed October 13, 2022. https://clinicaltrials.gov/ct2/show/NCT02977780

3. Study to evaluate safety, tolerability, and optimal dose of candidate GBM vaccine VBI-1901 in recurrent GBM subjects. ClinicalTrials.gov. Updated July 1, 2022. Accessed October 13, 2022. https://clinicaltrials.gov/ct2/show/NCT03382977?term=VBI-1901&draw=2&rank=1