Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, adult, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Adverse Events, Study Population, Human
Study Design and Methods: The GLOBRYTE study (GO43878; EU CT: 2023-503206-37-00) is a Phase III, open-label, multicenter, randomized, controlled trial that will evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (biomarkers) of glofitamab monotherapy in pts with R/R MCL, in comparison with an investigator’s choice of rituximab + bendamustine (BR) or rituximab + lenalidomide (R-Len). Pts with histologically confirmed R/R MCL who have received ≥1 prior line of systemic therapy (including a BTKi) and have an Eastern Cooperative Oncology Group performance status of 0–2 are eligible for enrollment. Exclusion criteria include leukemic, non-nodal MCL; prior CAR T-cell therapy or CD20xCD3 bispecific antibodies; primary or secondary central nervous system (CNS) lymphoma or history of CNS lymphoma; and current or prior CNS disease (including stroke or transient ischemic attack in the past 2 years and residual neurologic deficits, epilepsy, or CNS vasculitis). Eligible pts will be randomly assigned (1:1) to receive glofitamab or investigator’s choice of BR or R-Len stratified by line of therapy (1 vs ≥2) and response to last therapy (relapsed vs refractory). Pts will receive intravenous (IV) Gpt (2000mg) on Day (D) 1 of Cycle (C) 1, 7 days prior to the first glofitamab dose (Gpt may be split over 2 days as 1000mg doses if needed: the second 1000mg dose must be administered ≥1 day before initial glofitamab treatment). Pts will receive glofitamab for a fixed duration of 12 cycles, unless progressive disease (PD) or unacceptable toxicity occurs earlier. Glofitamab IV SUD will be given on C1D8 (2.5mg), C1D15 (10mg), and then the target dose (30mg) on D1 of C2–12 (21-day cycles). Pts randomized to the investigator’s choice will receive 375mg/m2 IV rituximab on D1 in combination with either 90mg/m2 IV bendamustine on D1–2 of each cycle (BR for six cycles) or 20mg/day oral lenalidomide on D1–21 of each cycle (R-Len until PD); the cycle length for BR or R-Len is 28 days. Crossover to glofitamab from the investigator’s choice is permitted in pts with radiologic confirmation of PD (Figure). The primary endpoint is progression-free survival (PFS) determined by independent review committee (IRC). Treatment comparisons will be made with a 2-sided, level 0.05 stratified log-rank test. Secondary endpoints include overall survival (OS); IRC- and investigator-assessed CR rate, objective response rate, duration of response, and duration of CR; PFS (investigator-assessed); safety; health-related quality of life including time to deterioration in physical functioning or fatigue evaluated by the EORTC QLQ-C30; glofitamab PK; and immune response to glofitamab (including presence of anti-drug antibodies). Response will be determined according to Lugano criteria (Cheson et al. J Clin Oncol 2014). Stratified hazard ratios with 95% confidence intervals (95% CI) will be calculated for PFS and OS, and odds ratios (95% CI) will be calculated for the difference in CR rate and overall response rate between treatment arms. Predictive and prognostic biomarkers (to characterize high-risk subgroups and minimal residual disease kinetics) will also be explored. An estimated 80 sites globally will enroll approximately 182 pts with R/R MCL (glofitamab n=91; BR or R-Len n=91 total) starting in Oct–Nov 2023 (APAC, US, and EU regions).
Disclosures: Phillips: Abbvie, Bayer: Research Funding; Abbvie, AstraZeneca, Bayer, Beigene, BMS, Cardinal Health, Epizyme, Incyte, Karyopharm, Pharmacyclics, Seattle Genetics: Consultancy. Matasar: Regeneron: Honoraria, Other: Stipends; Kite: Honoraria, Other: Stipends; Teva: Consultancy; Immunovaccine Technologies: Honoraria; Epizyme: Other: Stipends; Celegene: Honoraria, Other: Stipends; BMS: Honoraria, Other: Stipend; Bayer: Consultancy, Honoraria, Research Funding; AstraZeneca: Honoraria, Other: Stipend; Takeda: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Consultancy; Merck: Current equity holder in private company; ADC Therapeutics: Consultancy, Honoraria, Other: Stipend; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunovaccine Technologies: Research Funding; Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Seagen: Honoraria, Other: stipends. Eyre: PeerView: Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Loxo Lilly: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medscape: Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Autolus: Consultancy; KITE: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eli Lilly and Company: Consultancy, Honoraria, Speakers Bureau; Loxo Oncology: Consultancy, Honoraria, Other, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Secura Bio: Membership on an entity's Board of Directors or advisory committees. Gine: Gilead: Consultancy, Honoraria; Miltenyi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genmab: Consultancy, Honoraria; Lilly: Consultancy, Honoraria. Filézac De L'Étang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Byrne: Roche Products Ltd: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Lundberg: F. Hoffmann La Roche Ltd: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Padovani: F. Hoffmann La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company. Boetsch: F. Hoffmann La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company. Bottos: F. Hoffmann La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company. Qayum: F. Hoffmann La Roche Ltd: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties.
OffLabel Disclosure: Glofitamab (Columvi) is a bispecific CD20-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory DLBCL, NOS or large B-cell lymphoma arising from FL, after two or more lines of systemic therapy.