Glofitamab Plus Immunochemotherapy Demonstrates Durable Efficacy with Manageable Safety in Relapsed/refractory Non‐hodgkin Lymphoma (R/R NHL): Update of a Phase Ib Study

Introduction: Glofitamab (Glofit) is a novel T-cell engaging bispecific antibody. Its 2:1 molecular configuration allows bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells, enabling combination with anti-CD20 antibody therapies such as rituximab. This Phase Ib study, NCT03467373, was designed to assess the safety, tolerability, and efficacy of Glofit in combination with R-CHOP in patients (pts) with R/R NHL prior to assessing this combination as a first-line therapy for pts with diffuse large B-cell lymphoma. Here, we present the updated efficacy and safety of Glofit plus R-CHOP in pts with R/R NHL from the dose-escalation phase after ≥2 years’ follow-up. Methods: Pts with R/R NHL received pretreatment with R- or obinutuzumab-CHOP in Cycle (C) 1. From C2 onwards, pts received R-CHOP plus increasing Glofit doses in separate cohorts (70 µg, 1800 µg, 10 mg, 30 mg) for 6–8 21-day cycles. In the 70 and 1800 µg cohorts, Glofit was given as a fixed dose on C2 Day (D) 8 onwards; in the 10 and 30 mg cohorts, pts received step-up dosing (SUD) in C2 (C2D8, 2.5 mg; C2D15, 10 mg; C3D8 onwards, target dose). Pts with a complete response (CR), partial response or stable disease were permitted to receive Glofit maintenance at their fixed or target dose every 2 months for up to 2 years. Efficacy endpoints included investigator-assessed best overall response rate (BORR) and duration of response (DoR). Results: At data cut-off (14 November 2022) 31 pts (23 follicular lymphoma [FL]; 6 transformed FL; 1 marginal-zone lymphoma; 1 mantle-cell lymphoma) had been enrolled and treated with Glofit plus R-CHOP (SUD, n = 20; fixed dose, n = 11). Median time on study was 30.7 months (range: 1–47); median age was 62 years (range: 34–78); median prior lines of therapy was 2 (range: 1–5). In the fixed-dose cohort, BORR during treatment was 82% (9/11 pts) and complete metabolic response (CMR) rate was 64% (7/11 pts). The median DoR and duration of complete response (DoCR; months) were not reached (NR; 95% CI: 6.1– not estimable [NE] for DoR and DoCR; Figure); median progression-free survival (PFS) was NR (95% CI: 7.7–NE). In the SUD cohort, the BORR during treatment was 95% (19/20 pts); CMR rate was 95% (19/20 pts). The median DoR was 28.4 months (95% CI: 21.6–NE), median DoCR was 25.4 months (95% CI: 17.9–NE; Figure); median PFS was 30.7 months (95% CI: 14.6–NE). Grade (gr) ≥3 adverse events (AEs) occurred in 29/31 pts (94%); serious AEs occurred in 23/31 pts (74%); 3 pts (10%) had fatal AEs (n = 2, COVID-19 pneumonia; n = 1, acute myeloid leukemia). Six pts (19%) withdrew from treatment due to an AE; cytokine release syndrome (CRS) occurred in 16/31 pts (52%; gr 1/2, 12 pts; gr 3/4, 4 pts). The research was funded by: Study NCT03467373 was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of all authors, was provided by Ellie Sherwood, MPhil, and Emily Lynch, PhD, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Immunotherapy, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. W. Townsend Employment or leadership position: University College London Hospitals Consultant or advisory role: F. Hoffmann-La Roche Ltd., Gilead, Takeda, and Incyte Honoraria: F. Hoffmann-La Roche Ltd., Takeda, Gilead, Incyte Research funding: F. Hoffmann-La Roche Ltd. Other remuneration: Travel, accommodation, expenses - F. Hoffmann-La Roche Ltd., Takeda M. S. Topp Consultant or advisory role: AbbVie, AstraZeneca, BMS, Genmab, Iovance, Janssen, KITE, F. Hoffmann-La Roche Ltd. Research funding: KITE, Regeneron, F. Hoffmann-La Roche Ltd. Other remuneration: Travel, accommodation, expenses - Gilead M. Dickinson Consultant or advisory role: Novartis, BMS, Gilead, F. Hoffmann-La Roche Ltd., Janssen, AbbVie, Genmab Honoraria: F. Hoffmann-La Roche Ltd., Amgen, MSD, Janssen, BMS, Novartis, Gilead, AbbVie Research funding: Novartis, F. Hoffmann-La Roche Ltd., Takeda, Celgene, MSD, AbbVie, Lilly Other remuneration: Travel, accommodation, expenses - F. Hoffmann-La Roche Ltd. M. Crump Honoraria: Kyte-Gilead, Novartis Research funding: Roche M. Hutchings Consultant or advisory role: Takeda, F. Hoffmann-La Roche Ltd., Genmab, Janssen, AbbVie Research funding: Celgene, Genmab, F. Hoffmann-La Roche Ltd., Takeda, Novartis, Janssen, Merck, AbbVie, AstraZeneca M. Tani Consultant or advisory role: AbbVie, Kiowa-Kirin, Incyte A. Mehta Consultant or advisory role: Kite-Gilead, BMS, SeaGen, AstraZeneca, Incyte/Morphosis, Kyowa Kirin, BeiGene, F. Hoffmann-La Roche Ltd./Genetech, Inc. Research funding: Incyte, Takeda, forty seven inc/Gilead, Juno pharmaceuticals/BMS, Celgene/BMS, Oncotartis, Innate pharmaceuticals, Seattle Genetics, TG Therapeutics, Affimed, Merck, Kite/Gilead, F. Hoffmann-La Roche Ltd./Genentech, Inc., ADC therapeutics, Miragen, Rhizen Pharmaceuticals Other remuneration: Speaker's Bureau - BeiGene, Incyte-Morphosis, Kite-Gilead, Kyowa Kirin, BMS A. Santoro Consultant or advisory role: Arqule, Sanofi, Incyte Other remuneration: speaker's bureau - Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Eli-Lilly, Sandoz, Eisai, Novartis, Bayer, MSD; membership on an entity's board of directors or advisory committees R. Marks Honoraria: Kite/Gilead, Merck Other remuneration: Travel, accommodation, expenses - Kite/Gilead P. Baumlin Employment or leadership position: F. Hoffmann-La Roche Ltd. D. Kaufman Employment or leadership position: Genentech, Inc./F. Hoffmann-La Roche Ltd. Stock ownership: Genentech, Inc./F. Hoffmann-La Roche Ltd. C. Wu Employment or leadership position: Roche (China) Holding Lmt. Stock ownership: F. Hoffmann-La Roche Ltd. Other remuneration: Travel, accommodation, expenses - Roche (China) Holding Lmt. M. Barrett Employment or leadership position: Roche Products Ltd. Stock ownership: F. Hoffmann-La Roche Ltd. K. Humphrey Employment or leadership position: F. Hoffmann-La Roche Ltd. Stock ownership: F. Hoffmann-La Roche Ltd. N. Qayum Employment or leadership position: F. Hoffmann-La Roche Ltd. Stock ownership: F. Hoffmann-La Roche Ltd. N. Ghosh Consultant or advisory role: Seagen, TG Therapeutics, AstraZeneca, Phamacyclics, Janssen, Bristol Myers Squibb, Gilead Sciences, BeiGene, Incyte, Karyopharm, Roche/Genentech, Syncopation Novartis, Loxo Oncology, Genmab, AdaptiveBiotech, ADC Therapeutics Research funding: TG Therapeutics, Genentech/Roche, Bristol Myers Squibb, Gilead, Morphosys, AbbVie Other remuneration: Speaker’s bureau - Gilead, AstraZeneca, Bristol Myers Squibb, Phamacyclics, Janssen, Epizyme