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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., Competing Interests: Lihua E. BuddeConsulting or Advisory Role: Roche/Genentech, Kite/Gilead, Novartis, BeiGeneResearch Funding: Merck, Amgen, MustangBio, AstraZenecaPatents, Royalties, Other Intellectual Property: CCR4 CAR T cells for treatment of patients with CCR4-positive cancer. CD33CAR for treatment of patients with CD33+ acute myeloid leukemiaTravel, Accommodations, Expenses: Roche/Genentech, Kite/Gilead, AstraZeneca Sarit AssoulineStock and Other Ownership Interests: Knight PharmaceuticalsHonoraria: Janssen Oncology, Pfizer, AbbVie, Novartis Canada Pharmaceuticals Inc, AstraZeneca, BMSConsulting or Advisory Role: Roche/Genentech, BeiGeneResearch Funding: Roche Canada (Inst), Takeda (Inst), Astex Pharmaceuticals (Inst), BeiGene (Inst), Novartis (Inst)Travel, Accommodations, Expenses: Roche Canada Laurie H. SehnHonoraria: Amgen, Apobiologix, AbbVie, Celgene, Gilead Sciences, Janssen-Ortho, Karyopharm Therapeutics, Kite, a Gilead company, Lundbeck, Merck, Roche/Genentech, Seattle Genetics, Takeda, Teva, TG Therapeutics, AstraZeneca, Acerta Pharma, morphosys, Incyte, Debiopharm Group, Sandoz-Novartis, Verastem, GenmabConsulting or Advisory Role: Celgene, AbbVie, Seattle Genetics, TG Therapeutics, Janssen, Amgen, Roche/Genentech, Gilead Sciences, Lundbeck, Amgen, apobiologix, Karyopharm Therapeutics, Kite, a Gilead company, Merck, Takeda, Teva, TG therapeutics, AstraZeneca, Acerta Pharma, MorphoSys, Incyte, Debiopharm Group, Sandoz-Novartis, Genmab, VerastemResearch Funding: Roche/Genentech (Inst), Teva (Inst) Stephen J. SchusterConsulting or Advisory Role: Celgene, Nordic Nanovector, Novartis, AbbVie, Acerta Pharma/AstraZeneca, Alimera Sciences, BeiGene, Juno Therapeutics, Loxo Oncology, Tessa Therapeutics, Genentech/RocheResearch Funding: Novartis (Inst), Pharmacyclics (Inst), Adaptive Biotechnologies (Inst), Merck (Inst), Genentech/Roche (Inst), Celgene (Inst), Juno Therapeutics (Inst), AbbVie (Inst), Incyte (Inst), TG Therapeutics (Inst), DTRM (Inst)Patents, Royalties, Other Intellectual Property: Patent Combination Therapies of CAR and PD-1 Inhibitors (via University of Pennsylvania with royalties to Novartis) Sung-Soo YoonHonoraria: NovartisConsulting or Advisory Role: Janssen, Takeda, Amgen, Celgene/JazzResearch Funding: Kyowa Kirin, Roche/Genentech, Yuhan Dok Hyun YoonHonoraria: Celltrion, Roche, Janssen, Amgen, Celgene, Samyang, Kirin Pharmaceuticals, TakedaConsulting or Advisory Role: Roche, Janssen, Amgen, Celgene, Green Cross, NovartisResearch Funding: Samyang, Abclone, Roche/Genentech, Janssen Oncology, Amgen, Genmab, Boryung, Eutilex Matthew J. MatasarStock and Other Ownership Interests: MerckHonoraria: Genentech, Roche, Bayer, Pharmacyclics, Seattle Genetics, Takeda, Immunovaccine, ADC Therapeutics, Karyopharm TherapeuticsConsulting or Advisory Role: Genentech, Bayer, Merck, Juno Therapeutics, Roche, Teva, Rocket Medical, Seattle Genetics, Daiichi Sankyo, TakedaResearch Funding: Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Rocket Medical, Seattle Genetics, Immunovaccine, IGM Biosciences , IGM BiosciencesTravel, Accommodations, Expenses: Genentech, Roche, Seattle Genetics, Bayer Francesc BoschConsulting or Advisory Role: AstraZeneca, Roche/Genentech, Janssen-Cilag, Lilly, AbbVie, Kite, a Gilead company, BeiGene, NovartisSpeakers' Bureau: AbbVie, Janssen, Roche, AstraZenecaResearch Funding: Janssen, AstraZeneca Loretta J. NastoupilHonoraria: Celgene, Gilead Sciences, Novartis, Bayer, Janssen Oncology, Pfizer, Gamida Cell, TG Therapeutics, Bristol Myers Squibb, ADC Therapeutics, Morphosys, Epizyme, GenmabResearch Funding: TG Therapeutics, Janssen Biotech, Celgene, Genentech/Roche, LAM Therapeutics, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Ian W. FlinnConsulting or Advisory Role: AbbVie (Inst), Seattle Genetics (Inst), TG Therapeutics (Inst), Verastem (Inst), Roche (Inst), Gilead Sciences (Inst), Kite, a Gilead company (Inst), Janssen (Inst), BeiGene (Inst), Takeda (Inst), AstraZeneca (Inst), Juno Therapeutics (Inst), Unum Therapeutics (Inst), MorphoSys (Inst), Nurix (Inst), Shanghai Yingli Pharmaceuticals (Inst), Genentech (Inst), Great Point Partners (Inst), Iksuda Therapeutics (Inst), Novartis (Inst), Pharmacyclics (Inst), Century Therapeutics (Inst), Hutchison MediPharma (Inst), SERVIER (Inst), Vincerx Pharma (Inst), Genmab (Inst), InnoCare Pharma (Inst)Research Funding: Acerta Pharma (Inst), Agios (Inst), Calithera Biosciences (Inst), Celgene (Inst), Constellation Pharmaceuticals (Inst), Genentech (Inst), Gilead Sciences (Inst), Incyte (Inst), Infinity Pharmaceuticals (Inst), Janssen (Inst), Karyopharm Therapeutics (Inst), Kite, a Gilead company (Inst), Novartis (Inst), Pharmacyclics (Inst), Portola Pharmaceuticals (Inst), Roche (Inst), TG Therapeutics (Inst), Trillium Therapeutics (Inst), AbbVie (Inst), ArQule (Inst), BeiGene (Inst), Curis (Inst), FORMA Therapeutics (Inst), Forty Seven (Inst), Merck (Inst), Pfizer (Inst), Takeda (Inst), Teva (Inst), Verastem (Inst), AstraZeneca (Inst), Juno Therapeutics (Inst), Unum Therapeutics (Inst), MorphoSys (Inst), Seattle Genetics (Inst), IGM Biosciences (Inst), Loxo (Inst), Rhizen Pharmaceuticals (Inst), Triact Therapeutics (Inst) Mazyar ShadmanConsulting or Advisory Role: AbbVie, Genentech, AstraZeneca, Sound Biologics, Cellectar, Pharmacyclics, BeiGene, Bristol Myers Squibb/Celgene, MorphoSys, Innate Pharma, Kite, a Gilead company, Adaptive Biotechnologies, EpizymeResearch Funding: Pharmacyclics (Inst), Acerta Pharma (Inst), Merck (Inst), TG Therapeutics (Inst), BeiGene (Inst), Celgene (Inst), Genentech (Inst), MustangBio (Inst), AbbVie (Inst), Sunesis Pharmaceuticals (Inst), Bristol Myers Squibb/Celgene Catherine DiefenbachStock and Other Ownership Interests: Gilead SciencesConsulting or Advisory Role: Seattle Genetics, Bayer, Bristol Myers Squibb, Genentech/Roche, Merck, Janssen, Celgene, MorphoSysResearch Funding: Seattle Genetics (Inst), Genentech (Inst), Incyte (Inst), LAM Therapeutics (Inst), Merck (Inst), Bristol Myers Squibb (Inst), Millennium (Inst), Roche/Genentech (Inst), Janssen (Inst), MEI Pharma (Inst), Trillium Therapeutics (Inst), Astex Pharmaceuticals (Inst)Expert Testimony: Jim Harmon Carol O'HearEmployment: Genentech/RocheStock and Other Ownership Interests: Genentech/RochePatents, Royalties, Other Intellectual Property: Antibody bufferingTravel, Accommodations, Expenses: Genentech/Roche Huang HuangEmployment: Roche Canada Antonia KwanEmployment: Genentech/RocheStock and Other Ownership Interests: Roche/Genentech Chi-Chung LiEmployment: Roche/GenentechStock and Other Ownership Interests: Roche/GenentechPatents, Royalties, Other Intellectual Property: Patent applications pertaining to the development and dosing of bispecific antibodies Emily C. PiccioneEmployment: GenentechStock and Other Ownership Interests: Roche/Genentech Michael C. WeiEmployment: Genentech/RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Genentech/Roche Shen YinEmployment: GenentechStock and Other Ownership Interests: GenentechTravel, Accommodations, Expenses: Genentech Nancy L. BartlettConsulting or Advisory Role: Seattle Genetics, Roche/Genentech, ADC Therapeutics, BTG, Acerta PharmaResearch Funding: Seattle Genetics (Inst), Kite, a Gilead company (Inst), Merck (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Immune Design (Inst), Forty Seven (Inst), Janssen (Inst), Pharmacyclics (Inst), Millennium (Inst), ADC Therapeutics (Inst), Autolus (Inst), Roche/Genentech (Inst), Pfizer (Inst), Affimed Therapeutics (Inst)No other potential conflicts of interest were reported.

Activities of enzymes involved in muscle damage [creatine kinase (CK) and aspartate aminotransferase (AST)] and levels of malondialdehyde (MDA) as a marker of oxidative stress were monitored in the plasma of 27 members of an America's Cup yachting crew. The preventive benefits of allopurinol on muscle damage were also tested. In racing period A, the crew was divided into two groups according to their tasks on board. Blood samples from all 27 sailors were obtained before the start of a 5-day fleet race, after the last race, and after the ten match races. In period B, crew members were divided at random into two groups. One group (13 participants) received 300 mg/day of allopurinol 3 h before racing. The other ten members received placebo. Blood samples were collected just before and after the second round of the Louis Vuitton Cup. All participants showed increased CK and AST activities after the racing period A. The increase in CK activity was highest in sailors involved in strenuous physical work. At the end of period A, plasma MDA levels were higher in all participants as compared with non-participant athletes. In period B, a significant decrease in CK activity, but not in AST, appeared among participants receiving allopurinol. Plasma MDA decreased in sailors treated with allopurinol, but this reduction did not reach statistical significance. America's Cup is a sailing sport with high physical demands, as shown by the increase in muscle-damage markers. Treatment with allopurinol appeared to decrease the levels of muscle damage markers.