Background: Glofitamab, a CD20xCD3 bispecific antibody, is approved as monotherapy for the treatment of patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy. In the Phase III STARGLO study, glofitamab in combination with gemcitabine and oxaliplatin (GemOx) showed statistically significant and clinically meaningful benefit in overall and progression-free survival over rituximab (R)-GemOx, in pts with R/R DLBCL ineligible for autologous stem cell transplant (ASCT; Abramson et al. EHA 2024). However, for pts with R/R DLBCL eligible for ASCT or CD19-directed chimeric antigen receptor (CAR) T-cell therapy, several cycles of salvage chemoimmunotherapy (e.g., R plus ifosfamide, carboplatin, and etoposide; R-ICE) may be required to achieve disease control prior to receiving these therapies. In pts with R/R DLBCL treated with R-ICE prior to ASCT, the overall response rate (ORR) was 63.5% and complete response rate was 38.0% (Gisselbrecht C, et al. J Clin Oncol 2010). As approximately 50% of pts with large B-cell lymphoma are refractory to salvage chemoimmunotherapy, an unmet need remains for optimizing pre-transplant salvage or CAR T-cell bridging therapies. Glofitamab has potential as a salvage treatment prior to CAR T-cell therapy as it targets different molecular antigens. Here, we present preliminary efficacy and safety data for glofitamab in combination with R-ICE (Glofit-R-ICE) in pts with R/R DLBCL eligible for ASCT or CAR T-cell therapy from a Phase Ib study (GO43693; NCT05364424).
Methods: Enrolled pts had DLBCL not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBCL), had received one prior line of therapy, had an Eastern Cooperative Oncology Group performance status of 0-1, had no CNS lymphoma involvement, and were eligible for ASCT or CAR T-cell therapy. Pts received obinutuzumab pretreatment (1000mg) on Cycle (C) 1 Day (D) 1, followed by ICE (standard dose; C1D1─3) and R-ICE (R 375mg/m2 C2D1; ICE C2D1─3) in 21-day cycles. Glofitamab was administered with step-up dosing in C1 (D8, 2.5mg; D15, 10mg) and at target dose (30mg) on C2D8. Pts could receive two or three cycles of Glofit-R-ICE at target dose, at the discretion of the investigator. The primary endpoint was investigator-assessed ORR by 2014 Lugano criteria, defined as the proportion of pts that achieved complete or partial metabolic response (CMR; PMR) within three cycles of Glofit-R-ICE. The interim efficacy-evaluable population was defined as all pts who received their first dose of study treatment at least 77 days before May 31, 2024. The safety-evaluable population was defined as all pts who had ≥1 dose of any study treatment.
Results: As of May 31, 2024, 41 pts provided informed consent and received study treatment. At baseline, median age was 66 years (range: 41-78) and 71.1% of pts were male. Most pts were White (65.9%; Asian: 7.3%; Black/African American: 7.3%; Native Hawaiian: 2.4%; unknown: 12.2%; and 4.9% not reported). Histological subtypes were confirmed as DLBCL NOS (70.7%), HGBCL with MYC and BCL-2/6 rearrangements (12.2%), HGBCL NOS (4.9%), and DLBCL activated B cell (2.4%); 9.8% were unknown. Extranodal disease was reported in 39.0% of pts. Median duration of glofitamab treatment was 28.0 days (range: 1-65). At the time of this interim analysis, the best ORR (CMR or PMR) was 78.1% (95% confidence interval [CI]: 60.0─90.7) and the CMR rate was 68.8% (95% CI: 50.0─83.9) in the interim efficacy-evaluable population (n=32). In the safety-evaluable population (n=41), the most common adverse event (AE) was cytokine release syndrome (CRS; 48.8%; Grade [Gr] 1, 29.3%; Gr 2, 19.5%); no Gr ≥3 CRS events were reported and all events resolved. No immune effector cell-associated neurotoxicity syndrome events were reported. Infections occurred in 19.5% of pts (Gr 1, 4.9%; Gr 2, 7.3%; Gr 3, 7.3%). Gr 3/4 AEs occurred in 61.0% of pts; platelet count decreased/thrombocytopenia was the most common (26.8%). Serious AEs were reported in 41.5% of pts. No Gr 5 AEs were reported. In total, one pt discontinued glofitamab treatment due to AEs. This pt had transformed Waldenstrom's macroglobulinemia with Gr 2 CRS and Gr 3 tumor lysis syndrome.
Conclusions: Glofit-R-ICE demonstrated high response rates in pts with R/R DLBCL eligible for ASCT or CAR T-cell therapy. The safety profile was manageable with a low treatment discontinuation rate. Updated data will be presented.
Diefenbach:Gilead Sciences: Current equity holder in publicly-traded company; OverT Therapeutics: Current equity holder in private company; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding; Celgene: Consultancy; FATE Therapeutics: Research Funding; Genentech/Roche: Consultancy, Research Funding; Genmab: Consultancy; I MAB: Consultancy; Incyte: Consultancy, Research Funding; MEI Pharma: Research Funding; Merck: Consultancy, Research Funding; Millenium: Research Funding; MorphoSys: Consultancy; Seattle Genetics: Consultancy, Research Funding; NYU Grossman School of Medicine/Perlmutter Cancer Center at NYU Langone Health: Current Employment. Caimi:Abcon Therapeutics: Current holder of stock options in a privately-held company; Recordati: Honoraria, Research Funding; Luminary Therapeutics: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Abbvie: Honoraria, Research Funding; Genmab: Research Funding; Sobi: Honoraria; BMS: Honoraria. Saba:AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Eli Lilly and Company: Consultancy, Research Funding, Speakers Bureau; MorphoSys AG: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Seagen Inc: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Merck: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; BeiGene USA: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kyowa Kirin: Research Funding. Vargas Madueno:Ipsen, Janssen: Consultancy; Genentech, Abbvie: Research Funding. Hamadani:Kite Pharma: Consultancy, Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; Omeros: Consultancy; AbbVie: Consultancy; Forte Biosciences: Consultancy; Autolus: Consultancy; Allovir: Consultancy; Caribou: Consultancy; CRISPR: Consultancy; Genmab: Consultancy; BMS: Consultancy; Sanofi Genzyme: Speakers Bureau; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Byondis: Consultancy; CRISPR: Speakers Bureau; DMC, Inc: Speakers Bureau; Genentech: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; Takeda: Research Funding. Fayad:Roche/Genentech: Research Funding; M.D. Anderson Cancer Center: Current Employment. Riedell:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sana Biotechnology: Consultancy; NektarTherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; CVS Caremark: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Fate Therapeutics: Research Funding; Xencor: Research Funding; CRISPR Therapeutics: Research Funding; Calibr: Research Funding; Cargo Therapeutics: Research Funding; Tessa Therapeutics: Research Funding; Adaptive Biotechnologies: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; Intellia Therapeutics: Membership on an entity's Board of Directors or advisory committees. Gillis-Smith:Abbvie: Research Funding; CarnaBio: Research Funding; F. Hoffmann-La Roche: Research Funding; Merck: Research Funding; Novartis: Research Funding. Simko:Apple, Inc.: Current equity holder in publicly-traded company; Roche Holding AG: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Orellana-Noia:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Filippou-Frye:Roche: Current Employment, Current equity holder in publicly-traded company. Kapp:Genentech, Inc.: Current Employment; Roche: Current equity holder in private company, Current equity holder in publicly-traded company. Relf: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; F-star Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Roche Products Ltd: Current Employment. Lundberg:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company, Patents & Royalties. Pinter-Brown:Acrotech: Speakers Bureau; Kiowa Kirin: Membership on an entity's Board of Directors or advisory committees.
All study therapy constituted investigational or off-label use
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal