Indirect Comparisons of the Efficacy of Epcoritamab Vs Glofitamab in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)

Background: Epcoritamab (epcor) is a first-in-class CD3xCD20 bispecific antibody (bsAb) approved for the treatment of 3L+ LBCL and follicular lymphoma. In the single-arm, phase 1/2, EPCORE NHL-1 trial (NCT03625037), epcor given until disease progression or unacceptable toxicity, demonstrated deep and durable responses, a median overall survival (OS) of 18.5 months, and a manageable safety profile in R/R LBCL. A second CD3xCD20 bsAb given as fixed-treatment duration, glofitamab (glofit), also demonstrated durable responses, conferring a median OS of 11.5 months in the pivotal study. Understanding how long-term outcomes compare among bsAb agents remains an important knowledge gap. With over 2 years of follow-up, in the absence of a head-to-head study, it is now relevant to compare the efficacy of these agents via indirect comparison. This study evaluated OS, progression-free survival (PFS), and duration of complete response (DoCR) of epcor vs glofit in R/R LBCL using data from the respective pivotal trials.

Methods: Two analyses were conducted to compare the efficacy of epcor and glofit. First, a matching-adjusted indirect treatment comparison (MAIC) was conducted using published OS and PFS data from the full cohort of the glofit pivotal trial (12.6 months of follow-up, Dickinson et al, 2022) and the epcor pivotal trial (EPCORE NHL-1). Piece-wise hazard ratios (HRs) were calculated when proportional hazards assumptions were not met. Baseline characteristic prognostic variables were selected based on literature, clinical judgement, and empirical statistical testing and were adjusted between epcor and glofit cohorts. Second, in sensitivity analyses, indirect comparisons were conducted using an updated analysis of glofit with longer follow-up that included DoCR, together with OS and PFS data starting at cycle (C) 3 with 32 months of follow-up (Hutchings et al, ASH 2023). Sensitivity analyses with longer follow-up could not be adjusted because glofit pt baseline characteristics were not presented. Aggregate OS and PFS curves for glofit were derived from subgroups of pts with complete response/partial response/no response (CR/PR/NR) at C3 (Hutchings et al, ASH 2023). Aggregate epcor OS and PFS curves were similarly derived for pts with CR/PR/NR at C3 without prior disease progression. Weighted Cox proportional-hazards models were used to estimate the OS and PFS HRs between the 2 comparators. The DoCR comparison included all glofit and epcor pts achieving CR. All comparisons used EPCORE NHL-1 data with a median of 37.1 months of follow-up.

Results: Pts enrolled into the pivotal trials of epcor and glofit were comparable by several key baseline characteristics before adjustment: age ≥65 y; male gender; Ann Arbor disease stage III-IV; primary refractory disease; refractory to most recent anti-CD20 therapy; previous chimeric antigen receptor T-cell therapy (CAR T); refractory to CAR T; and previous autologous stem cell transplant (ASCT). MAIC analysis revealed no significant difference in OS benefit from C1 until month 6 (HR 1.08, 95% CI 0.71, 1.64; P=0.72), but a demonstrable OS advantage from 6 months onward (HR 0.60, 95% CI 0.37, 0.98; P=0.04) in favor of epcor. An OS comparison starting at C3 with longer glofit follow-up demonstrated a consistent survival advantage in favor of epcor (HR 0.68, 95% CI 0.46, 1.01; P=0.05). The proportion of pts who received CAR T or ASCT subsequent therapy were similar for epcor and glofit (CAR T: 7.0% vs 8.9%; ASCT: 6.4% vs 6.3%) (National Institute for Health and Care Excellence Glofit Single Technology Appraisal, 2023). The MAIC analysis showed comparable PFS between epcor and glofit (HR 1.06, 95% CI 0.79, 1.41; P=0.71), although there was substantial censoring in the glofit PFS curve due to immature follow-up. With longer follow-up in the analysis starting at C3, with less censoring, the glofit PFS curve remained similar to the epcor PFS curve from C3 until month 6 (HR 0.67, 95% CI 0.42, 1.07; P=0.10), where separation of the PFS curves were observed favoring epcor (HR 0.56, 95% CI 0.33, 0.97; P=0.04). Median DoCR was longer for epcor (36.1 months) vs glofit (26.9 months).

Conclusion: These indirect treatment comparisons suggest that epcor may provide an overall survival benefit over glofit through longer PFS with more mature follow-up, potentially driven by longer DoCR. Survival data with longer follow-up in the full glofit cohort are needed to confirm these findings.

Allan:Celgene: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Epizyme: Consultancy; BeiGene: Consultancy, Speakers Bureau; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; AbbVie: Consultancy, Speakers Bureau. Fox:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Trial Steering Committee., Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Trial Steering Committee, Research Funding; SOBI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Research Funding; SERB: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ono: Consultancy, Membership on an entity's Board of Directors or advisory committees; MorphoSys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees; Atarabio: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead/Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Nowakowski:AbbVie Inc.: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy, Research Funding; Segen: Consultancy; Fate Therapeutics: Consultancy; MEI Pharma: Consultancy; Daiichi Sankyo: Consultancy; Debiopharm: Consultancy; F. Hoffmann-La Roche Limited: Consultancy; TG Therapeutics Inc: Consultancy; Constellation Pharmaceuticals: Consultancy; Kymera Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Incyte Corporation: Consultancy; Curis: Consultancy, Research Funding; MorphoSys AG: Consultancy, Research Funding; Selvita Inc: Consultancy; Genentech: Consultancy; Ryvu Therapeutics: Consultancy; Zai Laboratory: Consultancy; Bantam Pharmaceutical, LLC: Consultancy; Blueprint Medicines Corporation: Consultancy; ADC Therapeutics: Consultancy. Riedell:Genmab: Consultancy; Genentech/Roche: Consultancy, Research Funding; Kite/Gilead: Consultancy, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Research Funding; BeiGene: Consultancy; ADC Therapeutics: Consultancy; Sana Biotechnology: Consultancy; Nektar Therapeutics: Consultancy; Novartis: Consultancy, Research Funding; CVS Caremark: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; Intellia Therapeutics: Consultancy; Cellectis: Research Funding; Fate Therapeutics: Research Funding; CRISPR Therapeutics: Research Funding; Xencor: Research Funding; Calibr: Research Funding; Cargo Therapeutics: Research Funding; Tessa Therapeutics: Research Funding. Phillips:AbbVie: Research Funding; Pharmacyclics: Consultancy; Incyte: Consultancy; Genentech: Consultancy; Bayer: Consultancy, Research Funding; Gilead Sciences: Consultancy; Curis: Consultancy; Kite/Gilead: Consultancy; Celgene: Consultancy; Genmab: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Lymphoma & Myeloma Connect: Honoraria; Seattle Genetics: Consultancy, Honoraria; Pharmacyclics/Janssen: Research Funding. Wang:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of AbbVie. Alshreef:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Yu:AbbVie: Current Employment, Other: stockholder of AbbVie. Chen:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of AbbVie. Sail:AbbVie: Current Employment, Other: stockholder of AbbVie. Harb:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of AbbVie. Mutebi:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Chhibber:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Elliot:Genmab: Current Employment, Other: stockholder of Genmab. Atiya:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of Genmab. Thieblemont:Bristol Myers Squibb/Celgene: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria.