Fixed-Duration Zanubrutinib, Bendamustine, and Obinutuzumab (ZBG) in Treatment-Naïve Advanced Stage Follicular Lymphoma

Summary

This study investigates a fixed-duration regimen of zanubrutinib, bendamustine, and obinutuzumab (ZBG) in the treatment of treatment-naïve patients with advanced-stage follicular lymphoma. Patients will receive combination therapy with zanubrutinib, bendamustine, and obinutuzumab over 6 cycles, with each cycle lasting 28 days. The specific dosing schedule is as follows: Bendamustine 70 mg/m²: administered intravenously on Days 2-3 of Cycle 1, and on Days 1-2 of Cycles 2-6. Obinutuzumab 1000 mg: administered intravenously on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6 (every 28-day cycle). Zanubrutinib 160 mg orally twice daily (bid), continuously throughout Cycles 1-6. Treatment is discontinued after 6 cycles, with no subsequent maintenance therapy. Primary endpoint is 2-year PFS. Secondary endpoints include: CR rate after 6 cycles, ORR after 3 and 6 cycles MRD-negative rate after 3 and 6 cycles, OS, safety and tolerability.

Timeline

Start

2025-07-15

Primary completion

2028-07-15

Completion

2028-12-30

Publications

• Background Serna A, Navarro V, Iacoboni G, Lopez L, Sancho JM, Gonzalez-Barca E, Lopez-Garcia A, Cordoba R, Saez A, Jimenez-Ubieto A, Ferrero A, Garcia T, Sanchez A, Garcia C, Bosch M, Cabirta A, Jimenez M, Marin-Niebla A, Bosch F, Abrisqueta P. Rituximab maintenance after bendamustine-based treatment for follicular lymphoma and mantle cell lymphoma may exert a negative influence on SARS-CoV-2 infection outcomes. Haematologica. 2025 Jan 1;110(1):173-178. doi: 10.3324/haematol.2024.285219. No abstract available.
• Background Fowler NH, Nastoupil L, De Vos S, Knapp M, Flinn IW, Chen R, Advani RH, Bhatia S, Martin P, Mena R, Davis RE, Neelapu SS, Eckert K, Ping J, Co M, Beaupre DM, Neuenburg JK, Palomba ML. The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. Br J Haematol. 2020 May;189(4):650-660. doi: 10.1111/bjh.16424. Epub 2020 Mar 16.
• Background Zinzani PL, Mayer J, Flowers CR, Bijou F, De Oliveira AC, Song Y, Zhang Q, Merli M, Bouabdallah K, Ganly P, Zhang H, Johnson R, Martin Garcia-Sancho A, Provencio Pulla M, Trneny M, Yuen S, Tilly H, Kingsley E, Tumyan G, Assouline SE, Auer R, Ivanova E, Kim P, Huang S, Delarue R, Trotman J. ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma. J Clin Oncol. 2023 Nov 20;41(33):5107-5117. doi: 10.1200/JCO.23.00775. Epub 2023 Jul 28.
• Background Zinzani PL, Munoz J, Trotman J. Current and future therapies for follicular lymphoma. Exp Hematol Oncol. 2024 Aug 22;13(1):87. doi: 10.1186/s40164-024-00551-1.
• Background Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.
• Background Pott C, Jurinovic V, Trotman J, Kehden B, Unterhalt M, Herold M, Jagt RV, Janssens A, Kneba M, Mayer J, Young M, Schmidt C, Knapp A, Nielsen T, Brown H, Spielewoy N, Harbron C, Bottos A, Mundt K, Marcus R, Hiddemann W, Hoster E. Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study. J Clin Oncol. 2024 Feb 10;42(5):550-561. doi: 10.1200/JCO.23.00838. Epub 2023 Dec 14.
• Background Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trneny M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. doi: 10.1056/NEJMoa1614598.
• Background Casulo C, Byrtek M, Dawson KL, Zhou X, Farber CM, Flowers CR, Hainsworth JD, Maurer MJ, Cerhan JR, Link BK, Zelenetz AD, Friedberg JW. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study. J Clin Oncol. 2015 Aug 10;33(23):2516-22. doi: 10.1200/JCO.2014.59.7534. Epub 2015 Jun 29.
• Background Freedman A, Jacobsen E. Follicular lymphoma: 2020 update on diagnosis and management. Am J Hematol. 2020 Mar;95(3):316-327. doi: 10.1002/ajh.25696. Epub 2019 Dec 22.

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