Glofitamab monotherapy in pts with relapsed/refractory (R/R) large B-cell lymphoma (LBCL): Extended follow-up and landmark analyses from a pivotal phase II study.

Authors

Lorenzo Falchi

Lorenzo Falchi

Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY

Lorenzo Falchi , Carmelo Carlo-Stella , Franck Morschhauser , Martin Hutchings , Emmanuel Bachy , Guillaume Cartron , Cyrus Khan , Monica Tani , Joaquin Martinez-Lopez , Nancy L. Bartlett , Antonio Salar , Joshua Brody , Sirpa Leppä , Estafania Mulvihill , Linda Lundberg , James Relf , Yuying Xie , Alessia Bottos , Kathryn Humphrey , Michael Dickinson

Organizations

Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy, Hôpital Claude Huriez and CHU de Lille, Lille, France, Rigshospitalet, Copenhagen, Denmark, Centre Hospitalier Lyon-Sud, Lyon, France, CHU de Montpellier, Montpellier, France, Allegheny Health Network, Pittsburgh, PA, Ospedale Santa Maria delle Croci, Ravenna, Italy, Department of Hematology, Hospital Universitario 12 de Octubre, Complutense University, CNIO, CIBERONC, Madrid, Spain, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, Department of Hematology, Hospital del Mar, Passeig Maritim, 08003 Barcelona, Spain, Tisch Cancer Institute, New York, NY, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Roche Products Ltd, Welwyn Garden City, United Kingdom, F. Hoffmann-La Roche Ltd, Mississauga, ON, Canada, Peter MacCallum Cancer Centre, Royal Melbourne Hospital and The University of Melbourne, Melbourne, Vic, VIC, Australia

Research Funding

Pharmaceutical/Biotech Company
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

Background: Glofitamab is a CD3xCD20 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 1000mg obinutuzumab pretreatment 7 days prior to the first glofitamab dose. IV glofitamab was given as step-up doses: 2.5mg on Day (D) 1 of Cycle (C) 1, 10mg on C1D8 and 30mg (target dose) on D1 of C2–12 (21-day cycles). The primary endpoint was independent review committee (IRC)-assessed CR rate. PFS and OS post-hoc analyses were performed in responders (landmark for CR at C3 or end of treatment [EOT]). Results: As of Oct 10, 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. 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 ≥10mg 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. Conclusions: Glofitamab continued to demonstrate durable responses, with most pts in CR at EOT still in remission without new AEs. These data support the potential for favorable long-term outcomes with fixed-duration glofitamab for R/R LBCL. Updated analyses, including a larger population with a median CR follow up of approximately 20 months post-EOT, will be presented. Clinical trial information: NCT03075696.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Track

Hematologic Malignancies

Sub Track

Non-Hodgkin Lymphoma

Clinical Trial Registration Number

NCT03075696

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 7550)

DOI

10.1200/JCO.2023.41.16_suppl.7550

Abstract #

7550

Poster Bd #

101

Abstract Disclosures