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SurVaxM vaccine appears ‘very promising’ for newly diagnosed glioblastoma
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CHICAGO — SurVaxM demonstrated encouraging efficacy and immunogenicity among patients with newly diagnosed glioblastoma, according to results of a multicenter, single-arm phase 2 clinical trial presented at ASCO Annual Meeting.
SurVaxM (SVN53-67/M57-KLH, MimiVax) — developed at Roswell Park Comprehensive Cancer Center by Robert Fenstermaker, MD, chair of neurosurgery, and Michael Ciesielski, PhD, assistant professor of neurosurgery — is a novel peptide-based vaccine that targets survivin, a tumor-specific antigen nearly universally expressed in patients with glioblastoma.
“We essentially saw significant increase in both PFS and OS, which is noteworthy in patients with such a notoriously aggressive and treatment-resistant disease,” Fenstermaker, senior author on the study, said in a press release.
“We found in our prior experiences that when there is a greater expression of survivin in patients with glioblastoma, it’s a negative prognostic factor,” lead study author Manmeet Ahluwalia, MD, FACP, the Dean and Diane Miller Family endowed chair in neuro-oncology in the Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, professor in the department of medicine at Clinic Lerner College of Medicine of Case Western Reserve University, and a HemOnc Today Editorial Board Member, said in an interview. “Patients with higher levels of survivin do more poorly and their tumors tend to behave more aggressively than those patients with a lower expression of survivin.”
Researchers evaluated SurVaxM in 63 patients (median age, 60 years; range, 20-82; 60% men) enrolled at five U.S. cancer centers who underwent craniotomy with near-total resection, defined as less than 1 cm3 residual contrast enhancement. Patients received one 500 mcg dose of SurVaxM along with 100 mcg sargramostim after resection and chemoradiotherapy, followed by four biweekly doses with adjuvant temozolomide and then maintenance dosing every 12 weeks.
Median time to first immunization was 3 months (range, 1.9-4) from diagnosis.
Fifty-three percent of patients had methylated MGMT and 46% had unmethylated MGMT, with one patient without data. Immunohistochemistry showed patients’ survivin expression ranged from 1% to 40% (median, 12%).
Six-month PFS served as the study’s primary endpoint. Researchers also evaluated 12-month OS and immunologic response, assessed by detecting survivin-specific antibody (IgG) and CD8-positive T-cell levels.
Twelve-month OS from the time of diagnosis was 93.5% in the overall population, 96.9% in the methylated MGMT group and 89.4% in the unmethylated group.
“The benchmarks for 12-month OS with standard treatment are 75% for methylated MGMT and 55% for unmethylated MGMT, so these initial results are very promising,” Ahluwalia told HemOnc Today.
Measured from the time of the first dose of vaccine, median OS was 26 months and median PFS was 12.1 months. Patients in the methylated MGMT group showed a median OS of 28.2 months and median PFS of 16.3 months, and those in the unmethylated group achieved a median OS of 15.6 months and median PFS of 7.9 months.
“Glioblastoma still tends to be a disease with dismal outcomes. Most patients survive 15 to 16 months after diagnosis,” Ahluwalia said. “Typically, patients with the MGMT promoter methylator tend to do better, with a survival around 18 to 20 months, whereas those with unmethylated MGMT have worse outcomes, with survival of 13 months. But with this vaccine, we were surprised to see both those cohorts with benefit.”
Antibody titres showed 67% patients had an increase in survivin-specific IgG titre from prevaccine baseline to at least 1:10,000, and 27% had levels of at least 1:100,000. Researchers also observed CD8-positive T-cell responses.
Researchers observed no grade 3 or worse serious adverse events associated with SurVaxM. The most common grade 1 to grade 2 adverse event was injection site reaction, with 39 cases.
Based on these promising findings, researchers are planning two additional trials of SurVaxM.
One — which has received FDA approval and soon will begin enrollment — will evaluate the combination of the vaccine and an immune checkpoint blockade. Researchers also are planning a larger randomized trial of over 200 newly diagnosed patients that will randomly assign patients to the chemoradiation alone or with the vaccine.
“We saw disease stabilization and PFS that were much better than what is seen with historical cohorts, which gives us hope that we will try to validate these findings in the upcoming randomized trial,” Ahluwalia said. – by Alexandra Todak
Reference:
Ahluwalia M, et al. Abstract 2016. Presented at: ASCO Annual Meeting; May 29-June 4, 2019; Chicago.
Disclosure: Ahluwalia reports stock or other ownership in Doctible and MimiVax; honoraria from Elsevier, Prime Education and Prime Oncology; consultant/advisory roles with AbbVie, AstraZeneca, Bristol-Myers Squibb, CBT Pharmaceuticals, Flatiron Health, Kadmon, Karyopharm Therapeutics, Monteris Medical, Varian Medical Systems and VBI Vaccines; and research funding to his institution from AbbVie, AstraZeneca, Bayer, Boston Biomedical, Bristol-Myers Squibb, Incyte, Merck, MimiVax, Novartis, Novocure and Pharmacyclics. Please see the abstract for all other authors’ relevant financial disclosures.