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Glofitamab receives FDA approval for adults with relapsed or refractory DLBCL

On June 15, 2023, the U.S Food and Drug Administration (FDA) approved glofitamab for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of therapy.1

Glofitamab is a T-cell engaging bispecific antibody with a 2:1 configuration, targeting CD20 on B-cells and CD3 on T-cells2. It binds to CD20 with one of its binding regions fused to the CD3-binding region in a head-to-tail manner through a flexible linker for improved target-effector cell binding.2,3 This leads to the engagement and redirection of existing T-cells to eliminate malignant B-cells.1,2,3

The approval of glofitamab was based on results from the Phase I/II NP30179 trial (NCT03075696). The study evaluated the safety and efficacy of dose-escalated, single treatment glofitamab in 132 patients with R/R DLBCL, who were pretreated with prior therapies including CAR-T therapy (30%).1 In this study, patients received a fixed course of glofitamab for 8.5 months. Glofitamab achieved a significant durable response with a 56% overall response (OR; CI: 47-65) and a 43% complete response (CR; CI: 34-52). 68.5% (CI; 56.7-80.3) continued to respond to glofitamab for at least nine months, with an 18.4-month median duration of response.1 The most common adverse event was cytokine release syndrome (CRS), occurring in 70% of patients, followed by musculoskeletal pain (21%), fatigue (20%), and rash (20%).1 CRS was manageable using steroids and tocilizumab, with low rates of grade ≥ 3 events and no treatment withdrawals.2

At the 2022 ASH meeting, Manali Kamdar, MD, University of Colorado Cancer Center, Denver, CO, shared her enthusiasm for the development of glofitamab in R/R DLBCL: “I think this is an excellent treatment for patients. Hopefully one more [option] in our toolbox to take care of patients with R/R DLBCL.”

Glofitamab is the first and only FDA approved, off-the-shelf, CD20xCD3 T-cell engaging bispecific antibody given for a fixed duration of time for patients with R/R DLBCL and is expected to provide treatment options to patients with critical unmet needs.

References

  1. Genentech. FDA Approves Genentech’s Columvi, the First and Only Bispecific Antibody With a Fixed-Duration Treatment for People With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Available here. (Last accessed 16/06/2023)
  2. Hutchings M, Morschhauser F, Iacoboni G, et al. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell–Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. Journal of Clinical Oncology. 2021 Jun 20; 39(18):1959-1970.
  3. Bacac M, Colombetti S, Herter S, et al. CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies. Clinical Cancer Research. 2018 Feb 13;24(19):4785-4797.

Written by Lemuel Fulgencio
Edited by Elitsa Kamberska