GLOFITAMAB MONOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) LARGE B‐CELL LYMPHOMA (LBCL): EXTENDED FOLLOW‐UP AND LANDMARK ANALYSES FROM A PIVOTAL PHASE II STUDY (2023)

Introduction: Glofitamab is a CD20xCD3 bispecific antibody delivered in a fixed course of 12 three-weekly cycles. In a Phase II study (NCT03075696), glofitamab induced high complete response (CR) rates and had manageable toxicity in pts with R/R LBCL (Dickinson et al., 2022). We present an extended follow-up and a landmark analysis to assess the outcomes of pts in CR. Methods: Pts with LBCL and ≥2 prior therapies received 1000 mg obinutuzumab pretreatment 7 days prior to the first glofitamab dose. IV glofitamab was given as step-up doses: 2.5 mg on Day (D) 1 of Cycle (C) 1, 10 mg on C1D8 and 30 mg (target dose) on D1 of C2–12 (21-day cycles). The primary endpoint was independent review committee (IRC)-assessed CR rate. Progression-free survival (PFS) and overall survival (OS) post-hoc analyses were performed in responders (landmark for CR at C3 or end of treatment [EOT]). Results: As of 10 October 2022, 154 pts had received ≥1 dose of study treatment; baseline characteristics were as previously presented. Median number of prior therapies was 3 (range: 2–7); 33% had received prior CAR T-cells and 85% were refractory to their most recent regimen. Median time on study was 20.1 months (range: 0–32). The investigator (INV)-assessed CR rate (BOR) was 38% (40% by IRC) and overall response rate was 59% (52% by IRC). CR rates were consistent in pts with and without prior CAR-Ts (37% vs. 39%). After a median follow-up of 18.3 months (range: 0–30) in pts with a CR (BOR), most CRs (39/59; 66%) were ongoing. Median duration of CR (DoCR) was 24.1 months (95% CI: 19.8–NE); an estimated 70% of pts with a CR at any time remained in remission at 18 months (Figure). The 18-month OS rate was 41% (95% CI: 32.1–49.3). Landmark analyses at 1 year in pts with a CR pre-C3 (PFS rate: 71%, OS rate: 92%) and in pts with a CR at EOT (PFS rate: 80%, OS rate: 94%) showed that most pts were progression free and alive. In a cohort of 101 pts treated with glofitamab doses below the recommended Phase II dose but ≥10 mg with longer median CR follow-up (31 months, range: 1–49), the median DoCR was 30.1 months (95% CI: 5.5–NE) and 55% of pts were still in remission at data cut-off. This further confirms the highly durable responses achieved with glofitamab. CRS (by ASTCT) remained the most common adverse event (AE), occurring in 64% of pts and was mostly Grade (Gr) 1 (48%) or Gr 2 (12%); Gr 3 (3%) and Gr 4 (1%) events were uncommon. The incidence of AEs and serious AEs was stable compared with earlier analyses, with one new Gr 3 AE (acute kidney injury), one new Gr 2 neurologic AE (agitation) and no new glofitamab-related Gr 5 AEs reported. Encore Abstract—This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved. The research was funded by: NP30179 is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of all authors, was provided by Dikeledi Matlebjane, MSc of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. Keywords: aggressive B-cell non-Hodgkin lymphoma, immunotherapy Conflicts of interests pertinent to the abstract M. Dickinson Consultant or advisory role: Novartis, BMS, Gilead, Roche, Janssen, Abbvie, Genmab Honoraria: Roche, Amgen, MSD, Janssen, BMS, Novartis, Gilead, Abbvie Research funding: Novartis, Roche, Takeda, Celgene, MSD, Abbvie, Lilly Other remuneration: Travel, accommodation, expenses—Roche C. Carlo-Stella Employment or leadership position: Humanitas University Consultant or advisory role: Sanofi, ADC Therapeutics, Karyopharm Tx, Celgene/BMS, Roche, Merck Sharp & Dohme, Scenic Biotech, Novartis Honoraria: Celgene/BMS, Incyte, Roche, Janssen Oncology, Merck Sharp & Dohme, Astra-Zeneca, Gilead Research funding: Sanofi, ADC Therapeutics, Roche Other remuneration: Travel, accommodation, expenses—Takeda, Janssen Oncology F. Morschhauser Consultant or advisory role: Roche, Gilead, AbbVie Other remuneration: Membership on an entity's Board of Directors or advisory committees—Roche, Gilead, Novartis, Bristol-Myers Squibb, AbbVie, Genmab, Miltenyi, Allogenetherapeutics, AstraZeneca, Janssen L. Falchi Consultant or advisory role: Genmab, Abbvie, Roche/Genentech, ADC Therapeutics, Seattle Genetics, AstraZeneca Research funding: Roche, Genmab, Genentech Other remuneration: Travel, accommodation, expenses—Genmab E. Bachy Consultant or advisory role: Roche, Gilead Sciences, Incyte, Takeda, Novartis Honoraria: Gilead Sciences, Roche, Amgen, Janssen-Cilag, Novartis, Takeda, Incyte Research funding: Amgen, BMS Other remuneration: Travel, accommodation, expenses—Janssen-Cilag, Roche, Gilead Sciences, Incyte G. Cartron Consultant or advisory role: Roche, Celgene, Mabqi, MedxCell Honoraria: Gilead Sciences, Janssen, Celgene, Roche, Abbvie, Novartis Other remuneration: Travel, accommodation, expenses—Roche C. Khan Consultant or advisory role: Beigene, Astrazeneca, Morphosys Honoraria: Roche, Astrazenca, Beigene, SeaGen, Abbvie, JNJ, Gilead Sciences, BMS, Amgen, ADC Therapeutics, Karyopharm, GSK, Morphosys, Sanofi, Epizyme Research funding: Roche, Epizyme, Beigene, Astrazeneca Other remuneration: Speaker's Bureau—Roche, Astrazenca, Beigene, SeaGen, Abbvie, JNJ, Gilead Sciences, BMS, Amgen, ADC Therapeutics, Karyopharm, GSK, Morphosys, Sanofi, Epizyme; Travel, accommodation, expenses—F. Hoffmann-La Roche, Astrazenca, Beigene, SeaGen, Abbvie, JNJ, Gilead Sciences, BMS, Amgen, ADC Therapeutics, Karyopharm, GSK, Morphosys, Sanofi, Epizyme M. Tani Consultant or advisory role: Abbvie, Kiowa-Kirin, Incyte J. Martinez-Lopez Employment or leadership position: Complutense University Consultant or advisory role: Janssen/BMS/Novartis/Roche/Pfizer/Sanofi Research funding: BMS/Roche/Asltellas Other remuneration: Speaker's Bureau—Janssen/BMS/Novartis/Roche/Pfizer/Sanofi; Travel, accommodation, expenses—Janssen/Gilead N. Bartlett Consultant or advisory role: Seattle Genetics, Roche/Genentech, ADC Therapeutics, BTG, Acerta Pharma, Foresight Diagnostics Research funding: Seattle Genetics, Merck, Forty Seven, Janssen, Pharmacyclics, Millennium, ADC Therapeutics, Autolus, Roche/Genentech, Bristol-Myers Squibb/Celgene, Gilead/Kite Pharma A. Salar Research funding: Gilead, Roche, Abbvie Other remuneration: Speaker's bureau—BeiGene, BMS/Celgene, EusaPharma, Incyte, Janssen, Roche; Travel, accommodation, expenses—Janssen, Roche J. Brody Consultant or advisory role: Genentech, Merck, Kite/Gilead, SeaGen, ADC Therapeutics, Epizyme S. Leppä Consultant or advisory role: Genmab, GILEAD, Incyte, Novartis, Orion, Roche Honoraria: Gilead, Novartis Research funding: Bayer, Celgene, Genmab, Hutchmed, Novartis, Nordic Nanovector, Roche E. Mulvihill Employment or leadership position: Hoffmann-La Roche Stock ownership: Hoffmann-La Roche Other remuneration: Travel, accommodation, expenses—Hoffmann-La Roche L. Lundberg Employment or leadership position: F. Hoffmann-La Roche Stock ownership: F. Hoffmann-La Roche Other remuneration: Patent—F. Hoffmann-La Roche J. Relf Employment or leadership position: Roche Products limited Stock ownership: Roche, F-Star Therapeutics and Harpoon Therapeutics Y. Xie Employment or leadership position: Roche A. Bottos Employment or leadership position: F. Hoffmann-La Roche Stock ownership: F. Hoffmann-La Roche K. Humphrey Employment or leadership position: Roche Stock ownership: Roche M. Hutchings Consultant or advisory role: Takeda, Roche, Genmab, Janssen, Abbvie Research funding: Celgene, Genmab, Roche, Takeda, Novartis, Janssen, Merck, Abbvie, AstraZeneca