BACKGROUND: Heat shock protein peptide complex-96 (HSPPC-96) triggers adaptive and innate antitumor immune responses. The safety and efficacy of HSPPC-96 vaccination was examined in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: In this open-label, single-arm, phase I study, adult patients were vaccinated with HSPPC-96 in combination with the standard treatment for newly diagnosed GBM after surgical resection. Primary endpoints were frequency of adverse events and progression-free survival (PFS) at 6 months. Secondary endpoints included overall survival (OS), PFS, and tumor-specific immune response (TSIR). RESULTS: A total of 20 patients with newly diagnosed GBM were enrolled from September 2013 to February 2015. No grade 3 or 4 vaccine-related adverse events were noted. After a median follow-up of 42.3 months, PFS was 89.5% (95% CI, 66.9%-98.7%) at 6 months, median PFS was 11.0 months (95% CI, 8.2-13.8), and median OS was 31.4 months (95% CI, 14.9-47.9). TSIR was significantly increased by 2.3-fold (95% CI, 1.7-3.2) after vaccination. Median OS for patients with high TSIR after vaccination was >40.5 months (95% CI, incalculable) as compared with 14.6 months (95% CI, 7.0-22.2) for patients with low TSIR after vaccination (hazard ratio, 0.25; 95% CI, 0.071-0.90; P = 0.034). A multivariate Cox regression model revealed TSIR after vaccination as a primary independent predicator for survival. CONCLUSION: The HSPPC-96 vaccination, combined with the standard therapy, is a safe and effective strategy for treatment of newly diagnosed GBM patients. TSIR after vaccination would be a good indicator predicting the vaccine efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02122822. FUNDING: National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2014BAI04B01, 2014BAI04B02), Beijing Natural Science Foundation (7164253), Beijing Talents Fund (2014000021469G257), and Shenzhen Science and Technology Innovation Committee (JSGG20170413151359491).
BACKGROUND: Heat shock protein peptide complex-96 (HSPPC-96) triggers adaptive and innate antitumor immune responses. The safety and efficacy of HSPPC-96 vaccination was examined in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: In this open-label, single-arm, phase I study, adult patients were vaccinated with HSPPC-96 in combination with the standard treatment for newly diagnosed GBM after surgical resection. Primary endpoints were frequency of adverse events and progression-free survival (PFS) at 6 months. Secondary endpoints included overall survival (OS), PFS, and tumor-specific immune response (TSIR). RESULTS: A total of 20 patients with newly diagnosed GBM were enrolled from September 2013 to February 2015. No grade 3 or 4 vaccine-related adverse events were noted. After a median follow-up of 42.3 months, PFS was 89.5% (95% CI, 66.9%-98.7%) at 6 months, median PFS was 11.0 months (95% CI, 8.2-13.8), and median OS was 31.4 months (95% CI, 14.9-47.9). TSIR was significantly increased by 2.3-fold (95% CI, 1.7-3.2) after vaccination. Median OS for patients with high TSIR after vaccination was >40.5 months (95% CI, incalculable) as compared with 14.6 months (95% CI, 7.0-22.2) for patients with low TSIR after vaccination (hazard ratio, 0.25; 95% CI, 0.071-0.90; P = 0.034). A multivariate Cox regression model revealed TSIR after vaccination as a primary independent predicator for survival. CONCLUSION: The HSPPC-96 vaccination, combined with the standard therapy, is a safe and effective strategy for treatment of newly diagnosed GBM patients. TSIR after vaccination would be a good indicator predicting the vaccine efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02122822. FUNDING: National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2014BAI04B01, 2014BAI04B02), Beijing Natural Science Foundation (7164253), Beijing Talents Fund (2014000021469G257), and Shenzhen Science and Technology Innovation Committee (JSGG20170413151359491).
Authors: Orin Bloch; Courtney A Crane; Yelena Fuks; Rajwant Kaur; Manish K Aghi; Mitchel S Berger; Nicholas A Butowski; Susan M Chang; Jennifer L Clarke; Michael W McDermott; Michael D Prados; Andrew E Sloan; Jeffrey N Bruce; Andrew T Parsa Journal: Neuro Oncol Date: 2013-12-12 Impact factor: 12.300
Authors: Michael Weller; Patrick Roth; Matthias Preusser; Wolfgang Wick; David A Reardon; Michael Platten; John H Sampson Journal: Nat Rev Neurol Date: 2017-05-12 Impact factor: 42.937
Authors: Alessandro Testori; Jon Richards; Eric Whitman; G Bruce Mann; Jose Lutzky; Luis Camacho; Giorgio Parmiani; Giulio Tosti; John M Kirkwood; Axel Hoos; Lianng Yuh; Renu Gupta; Pramod K Srivastava Journal: J Clin Oncol Date: 2008-02-20 Impact factor: 44.544
Authors: Vincenzo Mazzaferro; Jorgelina Coppa; Matteo G Carrabba; Licia Rivoltini; Marcello Schiavo; Enrico Regalia; Luigi Mariani; Tiziana Camerini; Alfonso Marchianò; Salvatore Andreola; Roberto Camerini; Marco Corsi; Jonathan J Lewis; Pramod K Srivastava; Giorgio Parmiani Journal: Clin Cancer Res Date: 2003-08-15 Impact factor: 12.531
Authors: Roger Stupp; Monika E Hegi; Warren P Mason; Martin J van den Bent; Martin J B Taphoorn; Robert C Janzer; Samuel K Ludwin; Anouk Allgeier; Barbara Fisher; Karl Belanger; Peter Hau; Alba A Brandes; Johanna Gijtenbeek; Christine Marosi; Charles J Vecht; Karima Mokhtari; Pieter Wesseling; Salvador Villa; Elizabeth Eisenhauer; Thierry Gorlia; Michael Weller; Denis Lacombe; J Gregory Cairncross; René-Olivier Mirimanoff Journal: Lancet Oncol Date: 2009-03-09 Impact factor: 41.316
Authors: E Jonasch; C Wood; P Tamboli; L C Pagliaro; S M Tu; J Kim; P Srivastava; C Perez; L Isakov; N Tannir Journal: Br J Cancer Date: 2008-03-25 Impact factor: 7.640
Authors: Paula Alcaide-Leon; Tracy L Luks; Marisa Lafontaine; Janine M Lupo; Hideho Okada; Jennifer L Clarke; Javier E Villanueva-Meyer Journal: J Neurooncol Date: 2019-11-14 Impact factor: 4.130
Authors: Maryam Rahman; W Gregory Sawyer; Scott Lindhorst; Loic P Deleyrolle; Jeffrey K Harrison; Aida Karachi; Farhad Dastmalchi; Joseph Flores-Toro; Duane A Mitchell; Michael Lim; Mark R Gilbert; David A Reardon Journal: Neuro Oncol Date: 2020-09-29 Impact factor: 12.300
Authors: Yang Zhang; Poorva Mudgal; Liuyang Wang; Haiyang Wu; Na Huang; Peter B Alexander; Zhixian Gao; Nan Ji; Qi-Jing Li Journal: Oncoimmunology Date: 2020-04-12 Impact factor: 8.110
Authors: Stephen C Frederico; John C Hancock; Emily E S Brettschneider; Nivedita M Ratnam; Mark R Gilbert; Masaki Terabe Journal: Front Oncol Date: 2021-05-10 Impact factor: 6.244