medRxiv : the preprint server for health sciences · 2026
Pembrolizumab, Temozolomide and HSPPC-96 Vaccine in Newly Diagnosed Glioblastoma Post-Chemoradiation: Results from a Multi-institutional, Phase 2, Randomized, Placebo-Controlled Trial.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ozer Byram H, Lindhorst Scott M, Merrell Ryan T, Trevino Christopher R, Rudnick Jeremy D, Avgeropoulos Nicolas G, Ramakrishna Naren, Khagi Simon, Rauf Yasmeen, Walbert Tobias, Pan Edward, Youssef Michael, Fink Karen L, Mandel Jacob J, Taylor Lynne P, Colman Howard, Dunbar Erin M, Paleologos Nina, Burton Eric C, Wu Jing, Leeper Heather E, Gonzalez Javier, Penas-Prado Marta, Raizer Jeffrey J, Veglia Eleonora, Craig Sandra, Yuan Ying, Chambers Claudia, Wall Kathleen, Grajkowska Ewa, Mendoza Tito, Armstrong Terri S, Gilbert Mark R
Аннотация
BACKGROUND: GBM is one of the most common and most aggressive brain tumors in adults, and upfront standard of care treatment has limited efficacy. Immune checkpoint inhibitor strategies have significantly improved outcomes in various solid tumors but have not proven effective in GBM, suggesting other strategies may be needed to realize their full potential.
METHODS: GBM patients were treated with upfront standard of care chemoradiation with temozolomide and pembrolizumab, followed by adjuvant temozolomide and pembrolizumab for six nine-week cycles. Depending on production of sufficient vaccine, patients were randomized into HSPPC-96 vaccine or placebo group (q4 weeks) while those with failed vaccine production continued on study unblinded as an ancillary group. The primary objective was overall survival at one year, and secondary endpoints were progression-free survival at six months, overall and progression-free survival, radiographic response, and tolerability by patient-reported outcomes and adverse event documentation.
RESULTS: 90 patients were screened, 32 were treated (8 vaccine, 9 placebo, 15 ancillary), and 26 were evaluable for radiographic responses prior to accrual termination. The study did not meet its primary endpoint of overall survival at one year (65.5% in vaccine group, 75% in placebo). Progression-free endpoints were mildly improved in the vaccine group but were not significant, and response rates were not significantly different. The regimen was well-tolerated and safe.
CONCLUSIONS: Though limited by early discontinuation, these findings do not support the combination of pembrolizumab and HSPPC-96 vaccine with standard of care therapy.
TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03018288.
METHODS: GBM patients were treated with upfront standard of care chemoradiation with temozolomide and pembrolizumab, followed by adjuvant temozolomide and pembrolizumab for six nine-week cycles. Depending on production of sufficient vaccine, patients were randomized into HSPPC-96 vaccine or placebo group (q4 weeks) while those with failed vaccine production continued on study unblinded as an ancillary group. The primary objective was overall survival at one year, and secondary endpoints were progression-free survival at six months, overall and progression-free survival, radiographic response, and tolerability by patient-reported outcomes and adverse event documentation.
RESULTS: 90 patients were screened, 32 were treated (8 vaccine, 9 placebo, 15 ancillary), and 26 were evaluable for radiographic responses prior to accrual termination. The study did not meet its primary endpoint of overall survival at one year (65.5% in vaccine group, 75% in placebo). Progression-free endpoints were mildly improved in the vaccine group but were not significant, and response rates were not significantly different. The regimen was well-tolerated and safe.
CONCLUSIONS: Though limited by early discontinuation, these findings do not support the combination of pembrolizumab and HSPPC-96 vaccine with standard of care therapy.
TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03018288.