PMID- 38072960 OWN - NLM STAT- MEDLINE DCOM- 20240124 LR - 20240202 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 30 IP - 1 DP - 2024 Jan TI - Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. PG - 229-239 LID - 10.1038/s41591-023-02726-5 [doi] AB - Relapsed/refractory aggressive large B cell lymphoma (LBCL) remains an area of unmet need. Here we report the primary analysis of a phase 1b/2 trial of outpatient mosunetuzumab (a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody-drug conjugate) in relapsed/refractory LBCL. The phase 2 component is a single arm of an ongoing multi-arm trial. The primary endpoint during dose expansion was independent review committee (IRC)-assessed best overall response rate. Secondary endpoints included investigator-assessed overall response rate, complete response, duration of response, progression-free survival and overall survival. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% confidence interval (CI): 48.8-69.0) and 45.9% (45/98; 95% CI: 35.8-56.3), respectively (median follow-up, 23.9 months). Median duration of complete was not reached (95% CI: 20.5-not estimable (NE)). Median progression-free survival was 11.4 months (95% CI: 6.2-18.7). Median overall survival was 23.3 months (95% CI: 14.8-NE). Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients. These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018 . CI - (c) 2023. The Author(s). FAU - Budde, Lihua E AU - Budde LE AUID- ORCID: 0000-0003-1464-5494 AD - City of Hope Comprehensive Cancer Center, Duarte, CA, USA. ebudde@coh.org. FAU - Olszewski, Adam J AU - Olszewski AJ AUID- ORCID: 0000-0002-6472-6658 AD - Brown University, Providence, RI, USA. FAU - Assouline, Sarit AU - Assouline S AD - Jewish General Hospital, McGill University, Montreal, Quebec, Canada. FAU - Lossos, Izidore S AU - Lossos IS AUID- ORCID: 0000-0002-9346-9013 AD - Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA. FAU - Diefenbach, Catherine AU - Diefenbach C AD - Perlmutter Cancer Center at NYU Langone Health, New York, NY, USA. FAU - Kamdar, Manali AU - Kamdar M AD - University of Colorado, Aurora, CO, USA. FAU - Ghosh, Nilanjan AU - Ghosh N AD - Hematologic Oncology and Blood Disorders, Atrium Health Levine Cancer Institute, Charlotte, NC, USA. FAU - Modi, Dipenkumar AU - Modi D AD - Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA. FAU - Sabry, Waleed AU - Sabry W AD - Saskatoon Cancer Center, Saskatoon, Saskatchewan, Canada. FAU - Naik, Seema AU - Naik S AD - Penn State Cancer Institute, Hershey, PA, USA. FAU - Mehta, Amitkumar AU - Mehta A AD - University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Nakhoda, Shazia K AU - Nakhoda SK AD - Fox Chase Cancer Center, Philadelphia, PA, USA. FAU - Smith, Stephen D AU - Smith SD AD - Fred Hutchinson Cancer Center, Seattle, WA, USA. FAU - Dorritie, Kathleen AU - Dorritie K AD - UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. FAU - Jia, Ting AU - Jia T AD - Roche (China) Holding Ltd, Shanghai, China. FAU - Pham, Song AU - Pham S AD - F. Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada. FAU - Huw, Ling-Yuh AU - Huw LY AD - Genentech, Inc., South San Francisco, CA, USA. FAU - Jing, Jing AU - Jing J AD - Genentech, Inc., South San Francisco, CA, USA. FAU - Wu, Hao AU - Wu H AD - Genentech, Inc., South San Francisco, CA, USA. FAU - Ead, Wahib S AU - Ead WS AD - Genentech, Inc., South San Francisco, CA, USA. FAU - To, Iris AU - To I AD - Genentech, Inc., South San Francisco, CA, USA. FAU - Batlevi, Connie Lee AU - Batlevi CL AD - Genentech, Inc., South San Francisco, CA, USA. FAU - Wei, Michael C AU - Wei MC AD - Genentech, Inc., South San Francisco, CA, USA. FAU - Chavez, Julio C AU - Chavez JC AUID- ORCID: 0000-0002-2045-6238 AD - Moffitt Cancer Center, Tampa, FL, USA. Julio.C.Chavez@moffitt.org. LA - eng SI - ClinicalTrials.gov/NCT03671018 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article DEP - 20231210 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - KG6VO684Z6 (polatuzumab vedotin) RN - 0 (Antibodies, Monoclonal) RN - 0 (Immunoconjugates) RN - 0 (Antineoplastic Agents) SB - IM MH - Humans MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Antibodies, Monoclonal MH - *Immunoconjugates/adverse effects MH - *Lymphoma, Large B-Cell, Diffuse/drug therapy MH - *Antineoplastic Agents/therapeutic use PMC - PMC10803244 COIS- L.E.B. reports research funding from Amgen, Merck and AstraZeneca and consulting fees from Genentech, Inc., AstraZeneca, AbbVie, Bristol Myers Squibb, Kite Pharma and Nurix. A.J.O. reports being a Clinical Research Scholar of the Leukemia & Lymphoma Society; research funding from Genentech, Inc., Precision Biosciences, Genmab, Artiva, Kymera Therapeutics and Schrodinger; and consulting fees from Genmab, Blue Cross and Blue Shield of Rhode Island, Schrodinger, ADC Therapeutics and BeiGene. S.A. reports consulting fees from Ipsen, F. Hoffmann-La Roche Ltd, Genentech, Inc., Janssen, BeiGene, Gilead Sciences, Novartis and AstraZeneca. C.D. reports research funding and consulting fees from Genentech, Inc./F. Hoffmann-La Roche Ltd. M.K. reports research funding from Novartis; consultancy fees from AbbVie, AstraZeneca, Celgene/Bristol Myers Squibb, Adaptive Biotechnologies, ADC Therapeutics, BeiGene, Genentech, Inc., Syncopation and Caribou Biosciences; speakers bureau for SeaGen; and Data Monitoring Committee for Celgene and Genentech, Inc. N.G. reports research funding from TG Therapeutics, Genentech, Inc./F. Hoffmann-La Roche Ltd, Bristol Myers Squibb, Gilead Sciences, MorphoSys, AbbVie and Pharmacyclics; consulting fees from SeaGen, TG Therapeutics, AstraZeneca, Phamacyclics, Janssen, Bristol Myers Squibb, Gilead Sciences, Kite Pharma, BeiGene, Incyte corporation, Lava Therapeutics, Genentech, Inc./F. Hoffmann-La Roche Ltd, Novartis, Loxo Oncology, AbbVie, Genmab, Adaptive Biotech and ADC Therapeutics; speakers bureau for AstraZenca, Janssen, Pharmacyclics, Kite Pharma, Bristol Myers Squibb and Epizyme; and member on the board of directors/advisory committee for F. Hoffmann-La Roche Ltd NHL solutions panel. D.M. reports research funding from Genentech, Inc., ADC Therapeutics, Genmab and Karyopharm Therapeutics; speakers bureau for BeiGene; consulting fees from AstraZeneca; and advisory board member for SeaGen, ADC Therapeutics and MorphoSys. W.S. reports honoraria for advisory boards from F. Hoffmann-La Roche Ltd, Amgen, Janssen, BeiGene, Novartis, Bristol Myers Squibb, Incyte corporation and AstraZeneca and conference attendance travel support from BeiGene. S.N. reports employment with Penn State Cancer Institute; research funding from Genentech and AbbVie; and honoraria from ADC Therapeutics. A.M. reports research funding from Incyte corporation, Takeda, Forty Seven/Gilead Sciences, Juno Pharmaceuticals/Bristol Myers Squibb, Celgene/Bristol Myers Squibb, Innate Pharmaceuticals, Seattle Genetics, TG Therapeutics, Affimed, Merck, Kite Pharma/Gilead Sciences, F. Hoffmann-La Roche Ltd/Genentech, Inc. and ADC Therapeutics; consulting fees from Gilead Sciences, Seattle Genetics, Incyte corporation, MorphoSys, TG Therapeutics, Kyowa Kirin, BeiGene, F. Hoffmann-La Roche Ltd/Genentech, Inc. and ADCT; and speakers bureau for Incyte corporation/MorphoSys, BeiGene, Ipsen and Kyowa Kirin. S.K.N. reports employment with Fox Chase Cancer Center; research funding from BTG/SERB; and honoraria from Bristol Myers Squibb, BTG/SERB and ADC Therapeutics. S.D.D. reports funding from ADC Therapeutics, AstraZeneca, Bayer, BeiGene, De Novo Biopharma, Enterome, Genentech Inc., Incyte corporation, Kymera Therapeutics, Merck, Sharp & Dohme corporation, MorphoSys, Nanjing Pharmaceuticals and Viracta Therapeutics; and personal financial interests in ADC Therapeutics, AstraZeneca, BeiGene, Karyopharm Therapeutics, Kite Pharma, Incyte corporation, Numab Therapeutics, AbbVie and Genentech, Inc. K.D. reports research funding from Genmab, Janssen, F. Hoffmann-La Roche Ltd, Bristol Myers Squibb and Kite Pharma/Gilead and honoraria from Janssen. T.J. reports employment with F. Hoffmann-La Roche (China) Holding Ltd. S.P. reports employment with F. Hoffmann-La Roche Ltd (Canada). L-Y.H., J.J., H.W. and W.S.E. report employment with Genentech, Inc. I.T. reports employment with, personal financial interest in and patents/patents pending for Genentech, Inc. C.L.B. and M.C.W. report employment with and personal financial interest in Genentech, Inc. J.C.C. reports consulting fees from Kite Pharma/Gilead Sciences, Novartis, Bristol Myers Squibb, Cellectar, Adicet, Genentech, Inc., AstraZeneca, BeiGene, AbbVie, Genmab, Janssen and ADC Therapeutics; honoraria from AstraZeneca, Eli Lilly and BeiGene; research support from Merck, Janssen and AstraZeneca; and Data and Safety Monitoring Board member for Atara and the National Cancer Institute. I.S.L. has no competing interests to declare. EDAT- 2023/12/11 00:42 MHDA- 2024/01/24 06:43 PMCR- 2023/12/10 CRDT- 2023/12/10 23:19 PHST- 2023/10/19 00:00 [received] PHST- 2023/11/16 00:00 [accepted] PHST- 2024/01/24 06:43 [medline] PHST- 2023/12/11 00:42 [pubmed] PHST- 2023/12/10 23:19 [entrez] PHST- 2023/12/10 00:00 [pmc-release] AID - 10.1038/s41591-023-02726-5 [pii] AID - 2726 [pii] AID - 10.1038/s41591-023-02726-5 [doi] PST - ppublish SO - Nat Med. 2024 Jan;30(1):229-239. doi: 10.1038/s41591-023-02726-5. Epub 2023 Dec 10.