A Phase I First-in-human Trial of Bvax (B-cell Vaccination) in Addition to Standard of Care Chemoradiotherapy for Newly Diagnosed Glioblastoma

Summary

The objectives of this phase I first-in-human trial are to evaluate safety, feasibility, and preliminary efficacy of an individualized Bvax vaccine in addition to standard of care chemoradiation in patients with newly diagnosed glioblastoma.

Timeline

Start

2026-09-01

Primary completion

2028-09-01

Completion

2030-09-01

Publications

• Background Zanetti M, Castiglioni P, Rizzi M, Wheeler M, Gerloni M. B lymphocytes as antigen-presenting cell-based genetic vaccines. Immunol Rev. 2004 Jun;199:264-78. doi: 10.1111/j.0105-2896.2004.00152.x.
• Background Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12.
• Background Wennhold K, Thelen M, Schlosser HA, Haustein N, Reuter S, Garcia-Marquez M, Lechner A, Kobold S, Rataj F, Utermohlen O, Chakupurakal G, Theurich S, Hallek M, Abken H, Shimabukuro-Vornhagen A, von Bergwelt-Baildon M. Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy. Cancer Immunol Res. 2017 Sep;5(9):730-743. doi: 10.1158/2326-6066.CIR-16-0236. Epub 2017 Aug 4.
• Background Trefzer U, Weingart G, Chen Y, Herberth G, Adrian K, Winter H, Audring H, Guo Y, Sterry W, Walden P. Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma. Int J Cancer. 2000 Mar 1;85(5):618-26. doi: 10.1002/(sici)1097-0215(20000301)85:53.0.co;2-z.
• Background Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2535-43. doi: 10.1001/jama.2015.16669.
• Background Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.
• Background Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
• Background Schultze JL, Michalak S, Seamon MJ, Dranoff G, Jung K, Daley J, Delgado JC, Gribben JG, Nadler LM. CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy. J Clin Invest. 1997 Dec 1;100(11):2757-65. doi: 10.1172/JCI119822.
• Background Rotte A, Frigault MJ, Ansari A, Gliner B, Heery C, Shah B. Dose-response correlation for CAR-T cells: a systematic review of clinical studies. J Immunother Cancer. 2022 Dec;10(12):e005678. doi: 10.1136/jitc-2022-005678.
• Background Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bahr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Jul 1;6(7):1003-1010. doi: 10.1001/jamaoncol.2020.1024.
• Background Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020. Neuro Oncol. 2023 Oct 4;25(12 Suppl 2):iv1-iv99. doi: 10.1093/neuonc/noad149.
• Background Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bahr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris AG, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 2023 Jan 5;25(1):123-134. doi: 10.1093/neuonc/noac099.
• Background Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 2022 Nov 2;24(11):1935-1949. doi: 10.1093/neuonc/noac116.
• Background Lee-Chang C, Miska J, Hou D, Rashidi A, Zhang P, Burga RA, Jusue-Torres I, Xiao T, Arrieta VA, Zhang DY, Lopez-Rosas A, Han Y, Sonabend AM, Horbinski CM, Stupp R, Balyasnikova IV, Lesniak MS. Activation of 4-1BBL+ B cells with CD40 agonism and IFNgamma elicits potent immunity against glioblastoma. J Exp Med. 2021 Jan 4;218(1):e20200913. doi: 10.1084/jem.20200913.
• Background Lee-Chang C, Bodogai M, Moritoh K, Olkhanud PB, Chan AC, Croft M, Mattison JA, Holst PJ, Gress RE, Ferrucci L, Hakim F, Biragyn A. Accumulation of 4-1BBL+ B cells in the elderly induces the generation of granzyme-B+ CD8+ T cells with potential antitumor activity. Blood. 2014 Aug 28;124(9):1450-9. doi: 10.1182/blood-2014-03-563940. Epub 2014 Jul 18.
• Background Lee-Chang C, Bodogai M, Moritoh K, Chen X, Wersto R, Sen R, Young HA, Croft M, Ferrucci L, Biragyn A. Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers. J Immunol. 2016 Apr 15;196(8):3385-97. doi: 10.4049/jimmunol.1502034. Epub 2016 Mar 16.
• Background Kugler A, Seseke F, Thelen P, Kallerhoff M, Muller GA, Stuhler G, Muller C, Ringert RH. Autologous and allogenic hybrid cell vaccine in patients with metastatic renal cell carcinoma. Br J Urol. 1998 Oct;82(4):487-93. doi: 10.1046/j.1464-410x.1998.00794.x.
• Background Kim EK, Seo HS, Chae MJ, Jeon IS, Song BY, Park YJ, Ahn HM, Yun CO, Kang CY. Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures. Gene Ther. 2014 Jan;21(1):106-14. doi: 10.1038/gt.2013.65. Epub 2013 Nov 14.
• Background Hegi ME, Stupp R. Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter--still a dilemma? Neuro Oncol. 2015 Nov;17(11):1425-7. doi: 10.1093/neuonc/nov198. Epub 2015 Sep 15. No abstract available.
• Background Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. doi: 10.1056/NEJMoa043331.
• Background Gonzalez NK, Wennhold K, Balkow S, Kondo E, Bolck B, Weber T, Garcia-Marquez M, Grabbe S, Bloch W, von Bergwelt-Baildon M, Shimabukuro-Vornhagen A. In vitro and in vivo imaging of initial B-T-cell interactions in the setting of B-cell based cancer immunotherapy. Oncoimmunology. 2015 Jun 17;4(9):e1038684. doi: 10.1080/2162402X.2015.1038684. eCollection 2015 Sep.
• Background Fuerst TR, Pierce BG, Keck ZY, Foung SKH. Designing a B Cell-Based Vaccine against a Highly Variable Hepatitis C Virus. Front Microbiol. 2018 Jan 15;8:2692. doi: 10.3389/fmicb.2017.02692. eCollection 2017.
• Background Domingues P, Gonzalez-Tablas M, Otero A, Pascual D, Miranda D, Ruiz L, Sousa P, Ciudad J, Goncalves JM, Lopes MC, Orfao A, Tabernero MD. Tumor infiltrating immune cells in gliomas and meningiomas. Brain Behav Immun. 2016 Mar;53:1-15. doi: 10.1016/j.bbi.2015.07.019. Epub 2015 Jul 26.
• Background Drean A, Goldwirt L, Verreault M, Canney M, Schmitt C, Guehennec J, Delattre JY, Carpentier A, Idbaih A. Blood-brain barrier, cytotoxic chemotherapies and glioblastoma. Expert Rev Neurother. 2016 Nov;16(11):1285-1300. doi: 10.1080/14737175.2016.1202761. Epub 2016 Jul 4.
• Background Brown CE, Hibbard JC, Alizadeh D, Blanchard MS, Natri HM, Wang D, Ostberg JR, Aguilar B, Wagner JR, Paul JA, Starr R, Wong RA, Chen W, Shulkin N, Aftabizadeh M, Filippov A, Chaudhry A, Ressler JA, Kilpatrick J, Myers-McNamara P, Chen M, Wang LD, Rockne RC, Georges J, Portnow J, Barish ME, D'Apuzzo M, Banovich NE, Forman SJ, Badie B. Locoregional delivery of IL-13Ralpha2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. Nat Med. 2024 Apr;30(4):1001-1012. doi: 10.1038/s41591-024-02875-1. Epub 2024 Mar 7.
• Background Bodogai M, O'Connell J, Kim K, Kim Y, Moritoh K, Chen C, Gusev F, Vaughan K, Shulzhenko N, Mattison JA, Lee-Chang C, Chen W, Carlson O, Becker KG, Gurung M, Morgun A, White J, Meade T, Perdue K, Mack M, Ferrucci L, Trinchieri G, de Cabo R, Rogaev E, Egan J, Wu J, Biragyn A. Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells. Sci Transl Med. 2018 Nov 14;10(467):eaat4271. doi: 10.1126/scitranslmed.aat4271.
• Background Biagi E, Rousseau R, Yvon E, Schwartz M, Dotti G, Foster A, Havlik-Cooper D, Grilley B, Gee A, Baker K, Carrum G, Rice L, Andreeff M, Popat U, Brenner M. Responses to human CD40 ligand/human interleukin-2 autologous cell vaccine in patients with B-cell chronic lymphocytic leukemia. Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6916-23. doi: 10.1158/1078-0432.CCR-05-0484.
• Background Arrieta VA, Chen AX, Kane JR, Kang SJ, Kassab C, Dmello C, Zhao J, Burdett KB, Upadhyayula PS, Lee-Chang C, Shilati J, Jaishankar D, Chen L, Gould A, Zhang D, Yuan J, Zhao W, Ling X, Burks JK, Laffleur B, Amidei C, Bruce JN, Lukas RV, Yamaguchi JT, Cieremans D, Rothschild G, Basu U, McCord M, Brat DJ, Zhang H, Cooper LAD, Zhang B, Sims P, Cloughesy TF, Prins R, Canoll P, Stupp R, Heimberger AB, Horbinski C, Iwamoto FM, Rabadan R, Sonabend AM. ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma. Nat Cancer. 2021 Dec;2(12):1372-1386. doi: 10.1038/s43018-021-00260-2. Epub 2021 Nov 29.

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Indications