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Protein-targeting vaccine extends survival in glioblastoma
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A vaccine that targets the protein survivin appeared safe and extended survival among patients with newly diagnosed glioblastoma, according to results from a phase 2 study presented at Society for Neuro-Oncology Annual Meeting.
“Survivin is a protein that inhibits the process of apoptosis and is expressed in cancer,” Manmeet S. Ahluwalia, MD, associate director and head of operations at Burkhardt Brain Tumor and Neuro-Oncology Center at Cleveland Clinic and a HemOnc Today Editorial Board Member, said in an interview. “Survivin has been shown to be a negative predictor of prognosis in cancer. For glioblastoma in particular, it has been shown that higher expression of survivin is associated with worse outcomes.”
SurVaxM (MimiVax) is a peptide vaccine that targets survivin. Phase 1 study results have shown the vaccine to be safe for patients with malignant gliomas.
Ahluwalia and colleagues conducted a phase 2 study that included 63 patients (median age, 60 years; 38 males) with newly diagnosed glioblastoma. All patients received concurrent temozolomide plus radiation, followed by adjuvant temozolomide plus SurVaxM.
Primary endpoints included 6-month PFS, 12-month OS and immune response. Secondary endpoints included safety and tolerability.
According to study results, nearly all patients (96.7%) remained progression free during the first 6 months with SurVaxM.
Moreover, 94.2% of patients remained alive 1 year after diagnosis, compared with only 65% of patients in a historical comparison group.
HemOnc Today spoke with Ahluwalia about the study and the potential implications of the results.
Question: What is unique about SurVaxM ?
Answer: Right now there is a lot of excitement about immunotherapy in cancer. However, until now, immune checkpoint blockade has not been shown to have great outcomes in glioblastoma. Still, there has been considerable interest in vaccines for glioblastoma and this vaccine targets survivin, which is present on cancer cells. The vaccine has been shown to be extremely well-tolerated in prior phase 1 trials.
Q: How did you conduct the study?
A: For this phase 2 trial, we decided to combine the vaccine with the standard of care. Patients with newly diagnosed glioblastoma who underwent surgical resection received chemotherapy and radiation for 6 weeks. In addition to this, patients received six cycles of chemotherapy plus the vaccine every 2 weeks for the induction phase, followed by the vaccine every 12 weeks until disease progression or intolerable toxicities.
Q: What did you find?
A: The results were fascinating. Survivin was present in all patients included in the study. The vaccine was extremely well-tolerated and resulted in better survival outcomes. The vaccine provided a great benefit for patients who had higher survivin expression, as it appears to blunt the negative association of survivin, which is a poor prognostic factor of glioblastoma. Despite treatments, most patients with glioblastoma treated with standard of care usually survive for 15 months to 18 months. What we were able to show in our cohort was that PFS was 11.4 months and median OS was 26 months. These results are promising and hypothesis-generating.
Q: What still needs to be confirmed before this vaccine can be used in practice?
A: Additional clinical trials in a randomized manner need to be performed, and they are planned for this year.
Q: What is next for research?
A: We plan to conduct two trials to further confirm the early promising activity. One trial will be a prospective, randomized, double-blind, placebo-controlled phase 2 trial of SurVaxM plus temozolomide for patients with newly diagnosed glioblastoma. The second trial will consist of a combination of SurVaxM plus pembrolizumab (Keytruda, Merck) for patients with recurrent glioblastoma. – by Jennifer Southall
Reference:
Ahluwalia MS, et al. Presented at: Society for Neuro-Oncology Annual Meeting; Nov. 15-18, 2018; New Orleans.
For more information:
Manmeet S. Ahluwalia, MD, can be reached at Cleveland Clinic, 2049 E. 100th St.,
Cleveland, OH 44195; email: ahluwam@ccf.org.
Disclosure: Ahluwalia reports consultant roles with AbbVie, AstraZeneca, Elsevier, Flatiron, Monteris Medical, Varian Medical Systems and VBI vaccines; research support from AbbVie, AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, Novocure and Pharmacyclics; and stock ownership in Doctible and MimiVax.