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603 Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies: 3-Year Follow-up from a Pivotal Phase II Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Immunotherapy
Hematology Disease Topics & Pathways:
non-Hodgkin lymphoma, Bispecific Antibody Therapy, indolent lymphoma
Sunday, December 10, 2023: 5:00 PM

Stephen J. Schuster, MD1, Laurie H. Sehn, MD, MPH2, Nancy L. Bartlett, MD3, Matthew Matasar, MD, MS4, Sarit Assouline, MD5, Pratyush Giri, MBBS6*, John Kuruvilla, MD7*, Mazyar Shadman, MD, MPH8*, Chan Y. Cheah, MBBS9,10, Sascha Dietrich, MD11*, Keith Fay, MBChB, FRACP, FRCPA12*, Matthew Ku, MBBS13*, Loretta J. Nastoupil, MD14, Michael C. Wei, MD, PhD15, Shen Yin, PhD15*, Iris To, PharmD15*, Jiangeng Huang, PhD15*, Antonia Kwan, MBBS, PhD15*, Elicia Penuel, PhD15 and Elizabeth Lihua Elizabeth Budde, MD, PhD16

1Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
2BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada
3Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
4Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
5Jewish General Hospital, Montreal, QC, Canada
6Royal Adelaide Hospital, Adelaide, Australia
7Princess Margaret Cancer Centre, Toronto, ON, Canada
8Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA
9The University of Western Australia, Perth, Australia
10Linear Clinical Research, Sir Charles Gairdner Hospital, Nedlands, Australia
11Heidelberg University Hospital, Heidelberg, Germany
12St Vincent's Hospital and Royal North Shore Hospital, Sydney, Australia
13St Vincent's Hospital, University of Melbourne, Melbourne, Australia
14MD Anderson Cancer Center, Houston, TX
15Genentech, Inc., South San Francisco, CA
16City of Hope National Medical Center, Duarte, CA

Background: Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. In a pivotal Phase II study (NCT02500407), mosunetuzumab demonstrated a high complete response (CR) rate with a manageable safety profile in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy (Budde et al. Lancet Oncol 2022). Mosunetuzumab is a fixed-duration treatment that can be administered in an outpatient setting. Here, we present updated data for patients with R/R FL and ≥2 prior lines of therapy, after 3 years of follow-up.

Methods: Eligible patients with R/R FL Grade (Gr) 1–3a and ≥2 prior therapies received intravenous mosunetuzumab in 21-day cycles with step-up dosing in Cycle (C) 1 (C1 Day [D] 1, 1mg; C1D8, 2mg; C1D15/C2D1, 60mg; C3D1 and onwards, 30mg). Hospitalization for treatment was not required. Patients achieving a CR by C8 completed treatment without additional cycles; patients with a partial response or stable disease received a total of 17 cycles. The primary endpoint was CR rate as determined by an Independent Review Committee (as best response; Cheson 2007 criteria). Duration of response (DOR), duration of complete response (DOCR), progression-free survival (PFS), event-free survival (EFS), and safety were secondary endpoints. Time to next treatment (TTNT), response to retreatment, biomarkers of minimal residual disease (MRD), and circulating B-cell counts were exploratory endpoints.

Results: Ninety patients with R/R FL were enrolled. As of May 2, 2023, median time on study was 37.4 (range: 2.0–48.0) months. Investigator-assessed best overall response and CR rates were 77.8% (95% CI: 67.8–85.9) and 60.0% (95% CI: 49.1–70.2), respectively. The median DOR was 35.9 months (95% CI: 20.7–not reached [NR]). Median DOCR was NR (95% CI: 33.0–NR); the estimated 30-month DOCR rate was 72.4% (95% CI: 59.2–85.6) (Table). Three years after the end of treatment, 57.1% of 70 responding patients were alive and disease progression-free. Median PFS was 24.0 months (95% CI: 12.0–NR) (Figure). The median TTNT was 37.3 months (95% CI: 18.0–NR); estimated EFS at 36 months was 51.8% (95% CI: 40.8–62.8). After initial mosunetuzumab treatment, 34/90 (37.8%) patients had received a new anti-lymphoma therapy, including 33/90 (36.7%) patients who received a new systemic treatment (8/33 [24.2%] of these patients received chimeric antigen receptor T-cell therapy); 8/90 (8.9%) had radiotherapy; 2/90 (2.2%) had excision of tumor; 2/90 (2.2%) had an allogeneic stem cell transplant; and 1/90 (1.1%) had an autologous stem cell transplant. Five patients received retreatment with mosunetuzumab, 3/5 of these patients had a CR. No new cytokine release syndrome (CRS) events, serious, or Gr ≥3 adverse events (AEs) were reported since the previous analysis (median follow-up of 28.3 months; Bartlett et al. ASH 2022). CRS events occurred in 44.4% of patients and 2.2% were Gr 3/4 in severity; all CRS events resolved. Overall AEs and serious AEs were comparable to the previous analysis (Bartlett et al. ASH 2022); febrile neutropenia was not reported. Forty-six (51.1%) patients experienced Gr 3/4 AEs related to mosunetuzumab; the rate of AEs leading to discontinuation was low (4.4%). Peripheral blood B-cell depletion following treatment with mosunetuzumab occurred in all patients, and recovery was observed after a median of 18 months following the end of treatment in patients with a sustained response using follow-up samples. MRD kinetics following mosunetuzumab therapy will be presented.

Conclusions: In this updated analysis, with a median follow-up of 37.4 months, durable responses continued to be observed with fixed-duration mosunetuzumab in patients with R/R FL. The manageable safety profile was consistent with previous reports. Evidence of B-cell recovery was observed after a median of 18 months following the end of treatment.

Disclosures: Schuster: Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Janssen Research & Development: Research Funding; Merck: Research Funding; Nordic Nanovector: Other: Scientific Advisory Committee; Genentech: Consultancy; Acerta: Consultancy; Novartis: Consultancy, Research Funding. Sehn: Merck: Consultancy; AbbVie: Consultancy; Amgen: Consultancy; Incyte: Consultancy; Genentech/Roche: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; BMS/Celgene: Consultancy; Kite/Gilead: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; Roche/Genentech: Research Funding; Teva: Research Funding. Bartlett: ADC Therapeutics, Foresight Diagnostics, Kite, F. Hoffmann-La Roche Ltd / Genentech, Inc., Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics, Autolus, BMS/Celgene, Forty Seven, Gilead/Kite Pharma, Janssen, Merck, Millennium, Pharmacyclics, F. Hoffmann-La Roche Ltd / Genentech, Inc., Seattle Genetics: Research Funding; Washington University School of Medicine: Current Employment. Matasar: Juno: Consultancy; Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Honoraria, Other: stipends; Regeneron: Honoraria, Other: Stipends; Kite: Honoraria, Other: Stipends; AstraZeneca: Honoraria, Other: Stipend; Merck: Current equity holder in private company; ADC Therapeutics: Consultancy, Honoraria, Other: Stipend; Immunovaccine Technologies: Honoraria; Takeda: Consultancy, Honoraria; Epizyme: Other: Stipends; Bayer: Consultancy, Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; BMS: Honoraria, Other: Stipend; Celegene: Honoraria, Other: Stipends; Teva: Consultancy; Janssen: Honoraria, Research Funding; Immunovaccine Technologies: Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Assouline: BeiGene: Consultancy; Novartis Canada: Research Funding; AbbVie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria; Roche-Genentech: Honoraria; Ipsen: Consultancy; Gilead: Honoraria; Palladin: Honoraria. Giri: Royal Adelaide Hospital: Current Employment. Kuruvilla: Karyopharm: Other: DSMB; F. Hoffmann-La Roche Ltd, Astra Zeneca, Merck: Research Funding; Abbvie, Amgen, AstraZeneca, BMS, Genmab, Gilead, Incyte, Janssen, Merck, Novartis, Pfizer, F. Hoffman-La Roche Ltd, Seattle Genetics: Honoraria; Abbvie, BMS, Gilead, Merck, F. Hoffmann-La Roche Ltd, Seattle Genetics: Consultancy. Shadman: Mustang Bio, BMS, Pharmacyclics, Genentech, Inc., AbbVie,TG Therapeutics, BeiGene, AstraZeneca, Genmab, MorphoSys/Incyte, Vincerx: Research Funding; AbbVie, Genentech, Inc., AstraZeneca, Pharmacyclics, BeiGene, BMS, MorphoSys/Incyte, Kite, Eli Lilly, Genmab, Mustang Bio, Regeneron, ADC therapeutics, Fate Therapeutics, Janssen, MEI Pharma: Consultancy; regeneron: Consultancy, Research Funding; Lilly: Consultancy; pharmacyclics: Consultancy, Research Funding; beigene: Consultancy, Research Funding; abbvie: Consultancy; genentech: Consultancy, Research Funding. Cheah: F. Hoffmann-La Roche Ltd, Janssen, Gilead, AstraZeneca, Lilly, TG therapeutics, Beigene, Novartis, Menarini, Daizai, Abbvie, Genmab. BMS: Honoraria; BMS, F. Hoffmann-La Roche Ltd, Abbvie; MSD, Lilly: Research Funding; F. Hoffmann-La Roche Ltd, Janssen, Gilead, AstraZeneca, Lilly, TG therapeutics, Beigene, Novartis, Menarini, Daizai, Abbvie, Genmab. BMS: Consultancy. Dietrich: F. Hoffmann-La Roche Ltd, Kite, Gilead and BeiGene: Honoraria; University Hospital of Heidelberg, Germany: Ended employment in the past 24 months; University Hospital of Duesseldorf, Germany: Current Employment. Ku: Antengene, Genor BioPharma, F. Hoffmann-La Roche Ltd: Consultancy; Clinical Haematologist St Vincent's Hospital, Melbourne: Current Employment. Nastoupil: AbbVie: Honoraria; Genentech, Inc., Genmab, Gilead/Kite, Janssen, Merck, Novartis, Takeda: Honoraria, Research Funding; Regeneron: Honoraria; ADC Therapeutics: Honoraria; DeNovo: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; AstraZeneca: Honoraria; Caribou Biosciences: Honoraria, Research Funding; Gilead Sciences/Kite Pharma: Honoraria, Research Funding. Wei: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Patents & Royalties. Yin: F. Hoffmann-La Roche Ltd / Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. To: Genentech, Inc.: Current Employment. Huang: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Kwan: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd / Genentch, Inc.: Current Employment. Penuel: Genentech, Inc. / F. Hoffman-La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company. Budde: ADC Therapeutics: Consultancy; AstraZeneca: Consultancy, Research Funding; Roche: Consultancy; Amgen: Research Funding; Merck: Research Funding; MustangBio: Research Funding; Novartis, Gilead, F. Hoffmann-La Roche Ltd, BeiGene, Genentech, Inc.: Consultancy.

*signifies non-member of ASH