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127 Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Evolution of Immunotherapeutic Regimens in B-cell Lymphomas
Hematology Disease Topics & Pathways:
Biological therapies, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Diseases, indolent lymphoma, Therapies, Lymphoid Malignancies
Saturday, December 11, 2021: 12:00 PM

L. Elizabeth Budde1, Laurie H. Sehn, MD2, Matthew Matasar, MD3, Stephen J. Schuster, MD4, Sarit Assouline, MD, MSc5, Pratyush Giri6*, John Kuruvilla7, Miguel Canales, MD8, Sascha Dietrich, MD9, Keith Fay10*, Matthew Ku, MBBS, FRACP, FRCPA, PhD11, Loretta J. Nastoupil, MD12, Michael C. Wei13*, Shen Yin13, Michelle Y. Doral13*, Chi-Chung Li13*, Huang Huang14*, Raluca Negricea15*, Elicia Penuel13*, Carol O’Hear13* and Nancy L. Bartlett, MD16

1City of Hope, Duarte, CA
2BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, BC, Canada
3Memorial Sloan Kettering Cancer Center, New York, NY
4Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
5Jewish General Hospital, Montreal, QC, Canada
6Royal Adelaide Hospital, Adelaide, Australia
7Princess Margaret Cancer Centre, Toronto, ON, Canada
8Hospital Universitario La Paz, Madrid, Spain
9Universitat Heidelberg, Heidelberg, Germany
10St Vincent's Hospital and Royal North Shore Hospital, Sydney, Australia
11St Vincent's Hospital, University of Melbourne, Melbourne, Australia
12MD Anderson Cancer Center, Houston, TX
13Genentech, Inc., South San Francisco, CA
14F. Hoffmann-La Roche Ltd, Mississauga, ON, Canada
15Roche Products Ltd, Welwyn Garden City, United Kingdom
16Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

Background: FL is associated with frequent relapses and decreasing progression-free intervals with successive lines of conventional therapy. Later-line treatments may be less effective due to refractory disease. Mosunetuzumab (Mosun) is a CD20xCD3 bispecific antibody (Ab) that redirects T cells to eliminate malignant B cells. In the dose-escalation phase of an ongoing Phase I/II study (NCT02500407), Mosun was highly active and well tolerated in R/R FL patients (pts) who had received ≥2 prior lines of therapy (3L+ R/R FL) when given IV with Cycle (C) 1 step-up dosing for mitigation of cytokine release syndrome (CRS; Assouline et al. ASH 2020). We present pivotal data from the same study from a large expansion cohort of 3L+ R/R FL pts who received Mosun monotherapy at the recommended Phase II dose (1/2/60/30mg).

Methods: 3L+ R/R FL pts were enrolled into a single-arm, pivotal expansion cohort. All pts had FL (Grade [Gr] 1–3a), ECOG PS ≤1, and were R/R to ≥2 prior lines of therapy including an anti (a)-CD20 Ab and an alkylator. Mosun was given IV in 21-day cycles with step-up dosing in C1 (C1 Day [D]1: 1mg; C1D8: 2mg; C1D15 and C2D1: 60mg; D1 C3+: 30mg). Pts who achieved a complete response (CR) by C8 discontinued therapy; those with a partial response or stable disease continued treatment for a total of 17 cycles, unless disease progression (PD) or unacceptable toxicity occurred. The primary endpoint was CR (as best response) rate by PET/CT assessed by an independent review facility (IRF) using standard response criteria (Cheson et al. J Clin Oncol 2007). No mandatory hospitalization was required.

Results: A total of 90 pts were enrolled (median age: 60 years, range: 29–90; 61.1% male). At entry, 76.7% had stage III or IV disease and 44.4% had FLIPI 3–5. Median number of prior lines of therapy was 3 (range: 2–10). In addition to aCD20 Abs and alkylators (all pts), prior cancer therapies included anthracyclines (82.2%), ASCT (21.1%), PI3K inhibitors (18.9%), IMiDs (14.4%), BTK inhibitors (6.7%), and CAR-Ts (3.3%). 68.9% of pts were refractory to their last therapy, 78.9% to any prior aCD20 Ab, and 53.3% to any prior aCD20 Ab and an alkylator (double refractory). 52.2% had PD within 24 months from the start of initial therapy (POD24).

As of March 15, 2021, median time on study was 12.9 months (range: 2.0–22.1). Anti-tumor activity was seen in most pts (Figure). Best objective response (ORR) and CR rates by IRF were 78.9% (71/90 pts) and 57.8% (52/90), respectively (Table); the median time to first response was 1.4 months. Best ORR and CR rates were generally consistent in pre-specified subgroups (Table), including POD24 (ORR: 83%; CR: 55%) and double-refractory pts (ORR: 69%; CR: 48%). Median duration of objective response and CR was not reached; 12-month event-free rates after first response were 65.4% (95% CI: 52.6–78.1%) in all responders and 80.1% (95% CI: 67.4–92.7%) in CR pts. Median PFS was 17.9 months (95% CI: 12.0–not estimable).

CRS (Lee et al. Biol Blood Marrow Transplant 2019) was the most common adverse event (AE; 44.4% of pts). CRS was mostly confined to C1 and generally low Gr (Gr 1: 25.6%; Gr 2: 16.7%). High Gr CRS was uncommon (Gr 3: 1 patient; Gr 4: 1 patient with FL in leukemic phase); no Gr 5 CRS occurred. In the 40 pts with CRS, tocilizumab was used in 7 pts and corticosteroids in 9 pts; all events resolved after a median duration of 3 days. Other common (≥20%) AEs were fatigue (36.7%), headache (31.1%), neutropenia and pyrexia (28.9% each), hypophosphatemia (22.2%), and pruritus (21.1%). Common (≥5%) Gr 3–4 AEs (66.7% overall) were neutropenia (26.6%), hypophosphatemia (13.3%), hyperglycemia and anemia (7.8% each), and elevated ALT (5.6%). Gr 3 neurologic events were uncommon (4.4%) and no Gr 4–5 events occurred. Common (≥5%) SAEs (45.6% overall) were CRS (23.3%, including 2.2% Gr 3–4 CRS). Two Gr 5 (fatal) AEs occurred (malignant neoplasm progression and unexplained death; both considered unrelated to Mosun by investigators). AEs leading to Mosun discontinuation were uncommon (4 pts; 4.4%).

Conclusions: Mosun induces deep and durable remissions in 3L+ R/R FL pts, including those with POD24 and/or double-refractory disease. High response rates are achieved (ORR: 78.9%; CR: 57.8%) and maintained for ≥12 months in the majority of pts. Mosun has a manageable safety profile, with C1 step-up dosing effectively mitigating CRS, enabling treatment without mandatory hospitalization. Mosun represents an active new therapy for 3L+ R/R FL.

Disclosures: Budde: Merck, Inc: Research Funding; Amgen: Research Funding; AstraZeneca: Research Funding; Mustang Bio: Research Funding; Novartis: Consultancy; Gilead: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; BeiGene: Consultancy; Genentech, Inc.: Consultancy. Sehn: Teva: Consultancy, Research Funding; Debiopharm: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Roche/Genentech: Consultancy, Research Funding; AbbVie: Consultancy; Acerta: Consultancy; Amgen: Consultancy; Apobiologix: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Incyte: Consultancy; Janssen: Consultancy; Kite: Consultancy; Karyopharm: Consultancy; Lundbeck: Consultancy; Merck: Consultancy; Morphosys: Consultancy; Sandoz: Consultancy; Seattle Genetics: Consultancy; Takeda: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy. Matasar: F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; Janssen: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding; Merck Sharp & Dohme: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Honoraria; Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rocket Medical: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; IGM Biosciences: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Schuster: Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Genentech/Roche: Consultancy, Research Funding; Tessa Theraputics: Consultancy; Loxo Oncology: Consultancy; Juno Theraputics: Consultancy, Research Funding; BeiGene: Consultancy; Alimera Sciences: Consultancy; Acerta Pharma/AstraZeneca: Consultancy; Adaptive Biotechnologies: Research Funding; Incyte: Research Funding; TG Theraputics: Research Funding; Nordic Nanovector: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Assouline: Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Roche/Genentech: Research Funding; Jewish General Hospital, Montreal, Quebec: Current Employment; Eli Lilly: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Current equity holder in publicly-traded company, Research Funding; Gilead: Speakers Bureau; Johnson&Johnson: Current equity holder in publicly-traded company. Giri: Royal Adelaide Hospital: Current Employment. Kuruvilla: AbbVie: Honoraria; Amgen: Honoraria; Antengene: Honoraria; Janssen: Honoraria, Research Funding; Merck: Honoraria; AstraZeneca: Honoraria, Research Funding; Medison Ventures: Honoraria; TG Therapeutics: Honoraria; Seattle Genetics: Honoraria; Incyte: Honoraria; Karyopharm: Honoraria, Other: Data and Safety Monitoring Board; Roche: Honoraria, Research Funding; Gilead: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; BMS: Honoraria. Canales: iQone: Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Incyte: Consultancy; Takeda: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Sandoz: Honoraria, Speakers Bureau; Eusa Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Gilead/Kite: Consultancy, Honoraria. Dietrich: University Hospital Heidelberg: Current Employment; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KITE/Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Fay: St Vincent's Hosptial, Sydney, Australia: Current Employment. Ku: Roche: Consultancy; Antegene: Consultancy; Genor Biopharma: Consultancy. Nastoupil: Epizyme: Honoraria, Research Funding; MorphoSys: Honoraria; Janssen: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; IGM Biosciences: Research Funding; Caribou Biosciences: Research Funding; Gilead/Kite: Honoraria, Research Funding; Denovo Pharma: Other: DSMC; Takeda: Honoraria, Other: DSMC, Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria; TG Therapeutics: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Wei: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Yin: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Doral: 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. Li: Genentech, Inc.: Current Employment, Current holder of individual stocks in a privately-held company. Huang: F. Hoffmann-La Roche Ltd: Current Employment. Negricea: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Penuel: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. O’Hear: F. Hoffmann-La Roche Ltd: Current holder of individual stocks in a privately-held company; Genentech, Inc.: Current Employment. Bartlett: Pharmacyclics: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding; Merck: Research Funding; Kite Pharma: Research Funding; Janssen: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Autolus: Research Funding; Affimed: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Washington University School of Medicine: Current Employment; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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

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