Lihua E Budde1, Sarit Assouline2, Laurie H Sehn3, Stephen J Schuster4, Sung-Soo Yoon5, Dok Hyun Yoon6, Matthew J Matasar7, Francesc Bosch8, Won Seog Kim9, Loretta J Nastoupil10, Ian W Flinn11, Mazyar Shadman12, Catherine Diefenbach13, Carol O'Hear14, Huang Huang15, Antonia Kwan14, Chi-Chung Li14, Emily C Piccione14, Michael C Wei14, Shen Yin14, Nancy L Bartlett16. 1. City of Hope National Medical Center, Duarte, CA. 2. Jewish General Hospital and McGill University, Montreal, Quebec, Canada. 3. BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, British Columbia, Canada. 4. Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA. 5. Seoul National University Hospital, Seoul, South Korea. 6. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 7. Memorial Sloan Kettering Cancer Center, New York, NY. 8. University Hospital Vall d'Hebron and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 9. Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea. 10. MD Anderson Cancer Center, Houston, TX. 11. Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN. 12. Fred Hutchinson Cancer Research Center, Seattle, WA. 13. Perlmutter Cancer Center at NYU Langone Health, New York, NY. 14. Genentech, Inc, South San Francisco, CA. 15. F. Hoffmann-La Roche Limited, Mississauga, Ontario, Canada. 16. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO.
Abstract
PURPOSE: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). METHODS: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response. RESULTS: Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n = 197), common adverse events (≥ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade ≥ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively. CONCLUSION: Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.
PURPOSE: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). METHODS: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response. RESULTS: Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n = 197), common adverse events (≥ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade ≥ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively. CONCLUSION: Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.
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