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1628 Subcutaneous Mosunetuzumab Is Active with a Manageable Safety Profile in Patients (pts) with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphomas (B-NHLs): Updated Results from a Phase I/II Study

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Diseases, Therapies, Lymphoid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Elizabeth L. Budde, MD, PhD1, Nancy L. Bartlett2*, Pratyush Giri3*, Stephen J. Schuster4*, Sarit Assouline5, Sung-Soo Yoon, MD, PhD6, Keith Fay7*, Matthew J. Matasar, MD, MS8, Norma C. Gutierrez9*, Paula Marlton, MD10, Martin Dreyling, MD11, Dok Hyun Yoon12*, Georg Hess, MD13*, John Radford, MD, FRCPath, FMedSci14*, Volker Wiebking15, Shen Yin15, Eva Cybulski15*, David C. Turner15*, Huang Huang16*, Mingzhu Zhou17*, Elicia Penuel15*, Michael C. Wei15* and Laurie H. Sehn, MD, MPH18

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
2Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
3Royal Adelaide Hospital, Adelaide, Australia
4Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
5Jewish General Hospital, McGill University, Montreal, QC, Canada
6Seoul National University Hospital, Seoul, Korea, Republic of (South)
7St Vincent's Hospital and Royal North Shore Hospital, Sydney, Australia
8Memorial Sloan Kettering Cancer Center, New York, NY
9Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, Spain
10Princess Alexandra Hospital and University of Queensland, Brisbane, Australia
11Ludwig-Maximilians-University Hospital Munich, Munich, Germany
12Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South)
13University Cancer Center Mainz, University Medical School of the Johannes Gutenberg-University, Mainz, Germany
14Christie NHS Foundation Trust, Manchester, United Kingdom
15Genentech, Inc., South San Francisco, CA
16F. Hoffmann-La Roche Ltd., Mississauga, ON, Canada
17F. Hoffmann-La Roche, Shanghai, China
18BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada

Background: Mosunetuzumab (Mosun), a CD20xCD3 T-cell engaging bispecific monoclonal antibody (Bi-mAb) that redirects T cells to eliminate malignant B cells, is the first Bi-mAb approved for R/R follicular lymphoma (FL; EMA 2022; Budde et al. Lancet Oncol 2022) and can be administered intravenously in the outpatient setting with a fixed treatment duration. A subcutaneous (SC) formulation that aims to improve safety and convenience is under evaluation. We present results for SC Mosun in a larger population with longer follow-up than previously reported (Bartlett et al. ASH 2021).

Methods: GO29781 is a Phase I/II, open-label, multicenter dose-escalation and expansion study of Mosun in pts with R/R B-NHL (NCT02500407). Pts with ≥1 prior line of systemic therapy (dose-escalation) or ≥2 prior lines (dose-expansion) were included. SC Mosun was administered with step-up dosing in Cycle (C) 1, then given on Day (D) 1 of subsequent 21-day cycles. The first 2 dose-escalation groups received Mosun 5mg on C1D1, 15mg or 45mg on C1D8, and 45mg on C1D15 and D1 from C2 onwards (5/15/45mg [Group 1] and 5/45/45mg [Group 2], respectively). A third group received Mosun 5mg on C1D1, 45mg on C1D8, 90mg on C1D15 and C2D1, and 45mg on D1 from C3 onwards (5/45/90/90/45mg [Group 3]). Pts with a complete response (CR) after 8 cycles completed therapy; pts with a partial response or stable disease continued treatment up to 17 cycles. Primary objectives included safety, tolerability and identification of the recommended Phase II dose.

Results: At data cut-off (May 20, 2022) 89 pts with R/R B-NHL received SC Mosun (Group 1: n=39, Group 2: n=47, Group 3: n=3). Most common histologies were diffuse large B-cell lymphoma (56%), transformed FL (19%) and FL (12%). Median (range) age was 68 years (24–88). Median number of prior systemic therapies was 3; 85.1% and 83.9% of pts were refractory to their last prior therapy or prior anti-CD20 therapy, respectively; 32.6% had received prior CAR T-cell therapy. Median (range) time on study was 9.9 months (m; 0.4–19.7) and cycles completed was 5 (1–17). No dose-limiting toxicities were observed in dose escalation. Most common all-Grade (Gr) adverse events (AEs) were injection-site reaction (62%; all Gr 1/2) and cytokine release syndrome (CRS; 27%; all Gr 1/2). Gr 3/4 and serious AEs were reported in 49% and 45% of pts, respectively. One AE led to Mosun discontinuation (COVID-19; Group 1). Gr 5 AEs were reported in 5 pts; none were considered Mosun-related by investigators (Group 1: n=3 [COVID-19 n=2; large intestine perforation n=1]; Group 2: n=2 [COVID-19 pneumonia and septic shock]). CRS was reported in 15/39 pts (38%), 8/47 pts (17%) and 1/3 pts in Groups 1, 2 and 3, respectively. Most CRS events occurred during C1. Median onset time since prior Mosun and median duration was 2 days (ranges 0–4 and 1–6, respectively). CRS events were low Gr (Gr 1: 18%; Gr 2: 9%; Figures 1 and 2) and all resolved; 2 pts (2%) received corticosteroids and 4 (5%) received tocilizumab for CRS. Neutropenia was reported in 19 pts (21%; Gr 3/4 in 17 [19%]) and febrile neutropenia in 1 pt (1%; Gr 3); median (range) neutropenia duration was 8 days (2–64). Serious infections were reported in 12 (14%) pts (Gr 3/4: n=8; Gr 5: n=4). Treatment-related neurological AEs possibly consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 3 pts (3%; all Gr 1: lethargy, memory impairment, and ICANS [confusion] with Gr 1 CRS); all resolved. Tumor flare was reported in 4 pts (4%; Gr 2: n=2; Gr 3: n=2); all resolved. All pts with indolent NHL (iNHL; all FL; 11/11) and 75/76 pts with aggressive NHL (aNHL) were enrolled ≥3 m prior to cut-off and included in the efficacy analysis. Overall response rate was 82% in iNHL and 36% in aNHL; CR rate was 64% in iNHL and 20% in aNHL, with 18/22 CRs (82%) ongoing at data cut-off. Median duration of response was 6.7 m (95% CI: 4.8–not estimable) in aNHL and not reached in iNHL (9-m event-free rate: 78% [95% CI: 51–100]).

Conclusions: SC Mosun demonstrated single-agent activity similar to the intravenous formulation in pts with R/R B-NHL. SC Mosun with C1 step-up dosing had a manageable safety profile, including low CRS rates across dose schedules. Based on exposure-response considerations regarding tolerability and clinical activity, 5/45/45mg was chosen as the recommended dose. SC Mosun could improve outcomes in R/R B-NHL while increasing convenience and reducing healthcare resource utilization.

Disclosures: Budde: Merck: Research Funding; Amgen: Research Funding; Amgen: Research Funding; AstraZeneca: Research Funding; Mustang Therapeutics: Research Funding; Ziopharm: Other: DMSC member for a phase 1 clinical; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees. Bartlett: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Washington University School of Medicine: Current Employment; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Autolos: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Forty Seven: Research Funding; Janssen: Research Funding; Kite Pharma: Research Funding; Merck: Research Funding; Millennium: Research Funding; Pharmacyclics: Research Funding. Schuster: AbbVie: Research Funding; Adaptive Biotechnologies: Research Funding; AstraZeneca: Consultancy; BeiGene: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; DTRM: Research Funding; Fate Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; Genmab: Consultancy; Incyte: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding; Legend Biotech: Consultancy; Loxo Oncology: Consultancy; Merck: Research Funding; MorphoSys: Consultancy; Mustang Biotech: Consultancy; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Pharmacyclics: Research Funding; Regeneron: Consultancy; Roche: Consultancy, Research Funding; TG Therapeutic: Research Funding. Assouline: Genentech/Roche, Astra Zeneca, Novartis, BMS, Jazz, Gilead, Amgen, Beigene, Abbvie, Paladin: Consultancy, Honoraria; Novartis: Research Funding. Yoon: Novartis: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Janssen Pharmaceutical: Consultancy; Chugai Pharmaceutical: Consultancy; Roche-Genetech: Research Funding; Yuhan Pharmaceutical: Research Funding; Kyowa Kirin: Research Funding; Astellas Pharma: Consultancy; Tikaros: Consultancy; Amgen: Consultancy. Matasar: Epizyme: Consultancy, Honoraria; Merck: Consultancy, Current equity holder in private company; Takeda: Consultancy, Honoraria; Teva: Consultancy; Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria; AstraZeneca: Consultancy; Rocket Medical: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; IGM Biosciences: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy; F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; IMV Therapeutics: Consultancy, Honoraria; Juno Therapeutics: Consultancy; TG Therapeutics: Consultancy; GlaxoSmithKline: Honoraria, Research Funding; ImmunoVaccine Technologies: Honoraria, Research Funding. Marlton: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dreyling: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly/Loxo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead/Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Abbvie: Research Funding; Beigene: Consultancy. Yoon: BMS: Honoraria; Amgen: Honoraria; Roche: Honoraria; Kirin Pharm: Honoraria, Research Funding; Janssen Pharmaceuticals: Honoraria, Research Funding; Celltrion: Honoraria, Research Funding; Sanofi: Research Funding; Beigene: Research Funding; Boryung pharmaceutical: Honoraria, Research Funding; SAMYANG Biopharm: Honoraria, Research Funding; Pharos iBio: Consultancy; Ab clone: Consultancy; GI cell: Consultancy; Novartis: Honoraria; Takeda: Honoraria; GSK: Honoraria; Celgene: Honoraria; GC Cell: Consultancy; AbbVie: Research Funding. Hess: BMS: Honoraria; BeiGene: Honoraria; Takeda: Consultancy; Roche: Consultancy, Honoraria, Research Funding; Novartis: Consultancy; MorphoSys: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grants, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel grants, Research Funding; Genmab: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; ADC Therapeutics: Consultancy; Pfizer: Research Funding; Celgene: Research Funding; Abbvie: Consultancy, Honoraria. Radford: The University of Manchester and Christie Hospital NHS Foundation Trust: Current Employment; ADC Therapeutics: Consultancy, Current equity holder in private company, Current holder of stock options in a privately-held company, Honoraria, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; Kite Pharma: Consultancy; Astrazenca: Current equity holder in private company, Current holder of stock options in a privately-held company. Wiebking: Genentech, Inc.: Current Employment; F. Hoffmann La Roche, Ltd.: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Yin: F. Hoffmann La Roche, Ltd.: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months; Genentech, Inc.: Current Employment, Patents & Royalties. Cybulski: Roche/Genentech: Current Employment, Current equity holder in publicly-traded company. Turner: GSK: Ended employment in the past 24 months; F. Hoffmann La Roche, Ltd.: Current holder of stock options in a privately-held company; Genentech, Inc.: Current Employment. Huang: F. Hoffmann La Roche, Ltd.: Current Employment. Zhou: FibroGen, Inc.: Ended employment in the past 24 months; F. Hoffmann La Roche, Ltd.: Current Employment. Penuel: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Wei: F. Hoffmann La Roche, Ltd.: Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties; Genentech, Inc.: Current Employment. Sehn: Chugai: Consultancy, Honoraria; Teva, Roche/Genentech: Consultancy, Honoraria, Research Funding; AbbVie, Acerta, Amgen, Apobiologix, AstraZeneca, BMS/Celgene, Debiopharm, Genmab, Gilead, Incyte, Janssen, Kite, Karyopharm, Lundbeck, Merck, Morphosys, Novartis, Sandoz, Seattle Genetics, Servier, Takeda, TG Therapeutics, Verastem: Consultancy; AbbVie, Acerta, Amgen, Apobiologix, AstraZeneca, BMS/Celgene, Gilead, Incyte, Janssen, Kite, Karyopharm, Lundbeck, Merck, Morphosys, Sandoz, Seattle Genetics, Servier, Takeda, TG Therapeutics, Verastem: Honoraria.

OffLabel Disclosure: Mosunetuzumab is a CD20xCD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent in the United States.

*signifies non-member of ASH