Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma. Issue 7 (1st March 2023)

• Record Type: Journal Article
• Authors: Ahluwalia, Manmeet S.; Reardon, David A.; Abad, Ajay P.; Curry, William T.; Wong, Eric T.; Figel, Sheila A.; Mechtler, Laszlo L.; Peereboom, David M.; Hutson, Alan D.; Withers, Henry G.; Liu, Song; Belal, Ahmed N.; Qiu, Jingxin; Mogensen, Kathleen M.; Dharma, Sanam S.; Dhawan, Andrew; Birkemeier, Meaghan T.; Casucci, Danielle M.; Ciesielski, Michael J.; Fenstermaker, Robert A.
• Is Part Of: Journal of clinical oncology. Volume 41:Issue 7(2023)
• Page Start: 1453
• Page End: 1465
• Publication Date: 2023-03-01
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.22.00996
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: Despite intensive treatment with surgery, radiation therapy, temozolomide (TMZ) chemotherapy, and tumor-treating fields, mortality of newly diagnosed glioblastoma (nGBM) remains very high. SurVaxM is a peptide vaccine conjugate that has been shown to activate the immune system against its target molecule survivin, which is highly expressed by glioblastoma cells. We conducted a phase IIa, open-label, multicenter trial evaluating the safety, immunologic effects, and survival of patients with nGBM receiving SurVaxM plus adjuvant TMZ following surgery and chemoradiation (ClinicalTrials.gov identifier: NCT02455557 ). METHODS: Sixty-four patients with resected nGBM were enrolled including 38 men and 26 women, in the age range of 20-82 years. Following craniotomy and fractionated radiation therapy with concurrent TMZ, patients received four doses of SurVaxM (500 μg once every 2 weeks) in Montanide ISA-51 plus sargramostim (granulocyte macrophage colony-stimulating factor) subcutaneously. Patients subsequently received adjuvant TMZ and maintenance SurVaxM concurrently until progression. Progression-free survival (PFS) and overall survival (OS) were reported. Immunologic responses to SurVaxM were assessed. RESULTS: SurVaxM plus TMZ was well tolerated with no serious adverse events attributable to SurVaxM. Of the 63 patients who were evaluable for outcome, 60 (95.2%) remained progression-free 6 months after diagnosis (prespecified primary end point). Median PFS was 11.4 months and median OS was 25.9 months measured from first dose of SurVaxM. SurVaxM produced survivin-specific CD8+ T cells and antibody/immunoglobulin G titers. Apparent clinical benefit of SurVaxM was observed in both methylated and unmethylated patients. CONCLUSION: SurVaxM appeared to be safe and well tolerated. The combination represents a promising therapy for nGBM. For patients with nGBM treated in this manner, PFS may be an acceptable surrogate for OS. A large randomized clinical trial of SurVaxM for nGBM is in progress.