MOSUNETUZUMAB DEMONSTRATES DURABLE RESPONSES IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA AND ≥2 PRIOR THERAPIES: UPDATED ANALYSIS OF A PIVOTAL PHASE II STUDY

Introduction: Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. In a pivotal Phase II study (NCT02500407), fixed-duration Mosun demonstrated a high rate of complete responses (CRs) and durable responses in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy. We report efficacy outcomes for pts who achieved CR by end-of-treatment (EOT), with a median follow-up of 28.6 months. Methods: Eligible pts with R/R FL (Grade [Gr] 1–3a) and ≥2 prior therapies were enrolled. Mosun was administered intravenously in 21-day cycles with step-up dosing in Cycle (C) 1 (C1 Day [D] 1, 1 mg; C1D8, 2 mg; C1D15/C2D1, 60 mg; C3D1 and onwards, 30 mg). Hospitalization for treatment was not required. Pts achieving CR by C8 completed treatment with no further cycles; pts with a partial response (PR) or stable disease received up to 9 further cycles. The primary endpoint was independent review committee-determined CR rate. The association between baseline (BL) total metabolic tumor volume (TMTV; derived using an AI-based model [Jemaa et al., 2022]) and clinical efficacy and safety was assessed. Results: Ninety pts were enrolled. Of these, 54 pts (60%) achieved CR as best response: 49 pts (54%) achieved CR at EOT; 1 pt with CR experienced disease progression (PD) in C8; and 4 pts achieved CR after EOT. In the 49 pts with CR at EOT, 82% had stage III/IV disease and median number of prior lines of therapy was 3 (range: 2–10). As of July 8, 2022, median time on study was 28.6 months. Among the 49 pts who achieved CR at EOT, median duration of CR (DOCR; investigator-assessed) was not reached (NR); 24-month DOCR rate after first CR was 65% (95% CI: 39–90). Median progression-free survival (PFS) was NR; 24-month PFS rate was 77% (95% CI: 63–91; Table). Two years after the end of fixed-duration treatment, 67% of these 49 pts remained free of PD or death. Of the 54 pts with CR as best response, 33 pts achieved their first CR by the first mandatory tumor assessment at 3 (±0.5) months (early CR) and 21 pts achieved their first CR after the 3 month assessment (late CR). Median duration of response (DOR) was NR in patients with an early or late CR. In pts with PR as best response (n = 16), median DOR was 4 months (95% CI: 3–7). No correlation was observed between BL TMTV and best overall response. A higher rate of Gr ≥2 cytokine release syndrome (CRS) was observed in pts with bone or bone marrow metabolic disease burden (n = 24) versus those without (n = 58; 33% vs. 14%, respectively). Conclusion: Fixed-duration Mosun monotherapy demonstrated a high CR rate at EOT in pts with R/R FL, with many pts remaining event-free 2 years after EOT. Exploratory analyses did not suggest an association between the timing of the first CR and DOR. TMTV at BL was not associated with response to Mosun. Gr ≥2 CRS events were more common in pts with bone or bone marrow metabolic disease burden. Encore Abstract—previously submitted to EHA 2023 The research was funded by: The NCT02500407 study is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of all authors, was provided by Ellie Sherwood, MPhil of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd. Keywords: immunotherapy, indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract L. H. Sehn Consultant or advisory role: Celgene, AbbVie, Seattle Genetics, TG Therapeutics, Janssen, Amgen, F. Hoffmann-La Roche/Genentech, Gilead Sciences, Lundbeck, Amge, Apobiologix, Karyopharm Therapeutics, Kite (a Gilead company), Merck, Takeda, Teva, TG Therapeutics, AstraZeneca, Acerta Pharma, Morphosys, Incyte, Debiopharm Group, Sandoz-Novartis, Genmab, Verastem Honoraria: Amgen, Apobiologix, AbbVie, Celgene, Gilead Sciences, Janssen-Ortho, Karyopharm Therapeutics, Kite (a Gilead company), Lundbeck, Merck, F. Hoffmann-La Roche/Genentech, Seattle Genetics, Takeda, Teva, TG Therapeutics, AstraZeneca, Acerta Pharma, Morphosys, Incyte, Debiopharm Group, Sandoz-Novartis, Verastem, Genmab Research funding: F. Hoffmann-La Roche/Genentech, Teva N. L. Bartlett Consultant or advisory role: Seattle Genetics, F. Hoffmann-La Roche/Genentech, ADC Therapeutics, BTG, Acerta Pharma, Foresight Diagnostics Research funding: Seattle Genetics, Merck, Forty Seven, Janssen, Pharmacyclics, Millennium, ADC Therapeutics, Autolus, F. Hoffmann-La Roche/Genentech, BMS/Celgene, Gilead/Kite Pharma M. Matasar Employment or leadership position: Memorial Sloan Kettering Cancer Center Consultant or advisory role: ADC Therapeutics, AstraZeneca, Bayer, Daiichi Sankyo, Epizyme, F. Hoffmann-La Roche Ltd., Genentech Inc., IMV Therapeutics, Juno Therapeutics, Karyopharm, Merck, MEI Pharma, Celgene, Seattle Genetics, TG Therapeutics, Teva, Bayer Stock ownership: Merck Honoraria: ADC Therapeutics, Bayer, Daiichi Sankyo, Epizyme, IMV Therapeutics, Janssen, MEI Pharma, Pharmacyclics, Genentech, Inc., F. Hoffmann-La Roche Ltd., Seattle Genetics Research funding: AstraZeneca, Bayer, Genentech, Inc., IGM Biosciences, Janssen, Pharmacyclics, F. Hoffmann-La Roche Ltd., Seattle Genetics S. J. Schuster Consultant or advisory role: Caribou Biotech, Genentech/Roche, Genmab, Kite Pharamaceuticals, Incyte, Legend Biotech, Morphosys, Mustang Biotech Nordic Nanovector, Novartis Honoraria: Novartis, Takeda Research funding: Merck, Genentech/Roche Other remuneration: Patent: Combination Therapies of CAR and PD-1 Inhibitors (royalties to Novartis); Travel, accommodation, expenses—Genentech/Roche, Novartis S. Assouline Consultant or advisory role: AbbVie, F. Hoffmann-La Roche Ltd., AstraZeneca, BMS, Paladin, Novartis, Pfizer, Janssen Honoraria: AbbVie, F. Hoffmann-La Roche Ltd., AstraZeneca, BMS, Paladin, Novartis, Pfizer, Janssen Research funding: Novartis J. Kuruvilla Consultant or advisory role: Abbvie, Antengene, BMS, Gilead, Karyopharm, Medison Ventures, Merck, F. Hoffmann-La Roche, Seattle Genetics Honoraria: Abbvie, Amgen, Astra Zeneca, BMS, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, F. Hoffmann-La Roche, Seattle Genetics Research funding: Canadian Cancer Society Research Institute (CCSRI), Canadian Institutes of Heath Research (CIHR), Leukemia and Lymphoma Society Canada, Princess Margaret Cancer Foundation, Roche, Astra Zeneca, Merck Other remuneration: Other—DSMB—Karyopharm, SAB—Lymphoma Canada M. Shadman Employment or leadership position: BMS (wife) Consultant or advisory role: AbbVie, Genentech Inc., AstraZeneca, Pharmacyclics, BeiGene, BMS, MorphoSys/Incyte, Kite, Eli Lilly, Genmab, Mustang Bio, Regeneron, ADC therapeutics, Fate Therapeutics and MEI Pharma Research funding: Mustang Bio, BMS, Pharmacyclics, Genentech Inc., AbbVie,TG Therapeutics, BeiGene, AstraZeneca, Genmab, MorphoSys/Incyte, Vincerx C. Y. Cheah Consultant or advisory role: F. Hoffmann-La Roche Ltd., Janssen, Gilead, AstraZenecca, Lilly, TG therapeutics, BeiGene, Novartis, Menarini, Daizai, AbbVie, Genmab. BMS Research funding: BMS, F. Hoffmann-La Roche Ltd., AbbVie, MSD, Lilly M. Ku Employment or leadership position: St Vincent’s Hospital, Melbourne, Australia Consultant or advisory role: Antengene, Genor BioPharma, F. Hoffmann-La Roche Ltd. L. Nastoupil Consultant or advisory role: Sirpant, Interius Bio Honoraria: ADC Therapeutics, Atara, BMS, Caribou Biosciences, Epizyme, Genentech, Inc., Gilead/Kite, Janssen, Novartis, Takeda Research funding: BMS, Caribou Biosciences, Epizyme, Genentech, Inc., Gilead/Kite, IGM Bioscience, Janssen, Novartis, Takeda Other remuneration: Travel, accommodation, expenses—Genentech, Inc./F. Hoffmann-La Roche Ltd. M. C. Wei Employment or leadership position: Genentech, Inc. Stock ownership: F. Hoffmann-La Roche Ltd. Other remuneration: Travel, accommodation, expenses—Genentech, Inc./F. Hoffmann-La Roche Ltd. S. Yin Employment or leadership position: Genentech, Inc. Stock ownership: Genentech, Inc. Other remuneration: Travel, accommodation, expenses—Genentech, Inc., Patents, royalties, other intellectual property—Genentech, Inc. I. To Employment or leadership position: Genentech, Inc. Stock ownership: Genentech, Inc. Other remuneration: Travel, accommodation, expenses—Genentech, Inc. N. Hu Employment or leadership position: F. Hoffmann-La Roche Ltd./Genentech, Inc. Stock ownership: F. Hoffmann-La Roche Ltd. J. Min Stock ownership: F. Hoffmann-La Roche Ltd. E. Penuel Employment or leadership position: Genentech, Inc. Stock ownership: Genentech, Inc. A. Belousov Employment or leadership position: Hoffmann La Roche LtD A. Coimbra Employment or leadership position: Genentech, Inc. Stock ownership: F. Hoffmann-La Roche Ltd. S. Jemaa Employment or leadership position: Genentech, Inc. Stock ownership: F. Hoffman-La Roche Ltd. B. Bender Employment or leadership position: Genentech, Inc. Stock ownership: F. Hoffman-La Roche Ltd. Other remuneration: Patents, royalties, other intellectual property—multiple Mosunetuzumab Patents D. Turner Employment or leadership position: Genentech, Inc./F. Hoffmann-La Roche Ltd., ended employment in past 24 months (GSK) Stock ownership: Genentech, Inc./F. Hoffmann-La Roche Ltd. Other remuneration: Leadership—Genentech, Inc./F. Hoffmann-La Roche Ltd. L. E. Budde Consultant or advisory role: F. Hoffmann-La Roche Ltd./Genentech, Inc. Kite/Gilead, Novartis, BeiGene Research funding: Merck, Amgen, MustangBio, AstraZeneca Other remuneration: Patents, 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 leukemia, Travel, accommodation, expenses—F. Hoffmann-La Roche/Genentech, Kite/Gilead