Named glofitamab and branded as Columvi, the treatment is specifically indicated in adult patients with relapsed or refractory DLBCL not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma. Eligible patients will have received two or more lines of systemic therapy, and are either unable to receive CAR-T cell therapy or have previously received CAR-T cell therapy.
CAR-T therapies have changed the landscape of treating rare forms of blood cancer such as DLBCL. They involve extracting a cancer patient’s T cells, genetically engineering them to hunt down cancer cells, and then reinfusing them. However, many patients don’t respond to these cell therapies. Additionally, the painstaking manufacturing process can take weeks to complete, which can be too long for patients with aggressive cancer. Therefore, more off-the-shelf options are desperately needed in late-stage DLBCL.
"DLBCL is an aggressive lymphoma that is the most commonly diagnosed subtype of non-Hodgkin lymphoma," stated Antonella Rizza, CEO, Lymphoma Canada in Roche’s public release. She added that the approval of the off-the-shelf treatment Columvi provides "an important new treatment option for relapsed and/or refractory DLBCL patients after multiple lines of therapy and ineligible for or having previously received CAR-T therapy."
How Columvi works
Columvi binds to cancerous immune B cells via the surface protein CD20. To tackle the cancer, the bispecific antibody also simultaneously binds to nearby immune T cells via the surface protein CD3. The T cells are then triggered to destroy the diseased B cells. Unlike other CD20-CD3 bispecific antibodies such as Roche’s mosunetuzumab (Lunsumio), Columvi is designed to work even when the patient has already been treated with competing anti-CD20 cancer treatments such as rituximab and obinutuzumab, making it easier to combine the therapies.
Additionally, Columvi is also the first of its kind to be dosed for a fixed duration in DLBCL. Many other cancer therapies are provided over a long time, which can be expensive and burdensome for patients.
The approval by Health Canada was based on results from a single-arm phase 1/2 study called NP30179, where 35.2% of DLBCL patients receiving Columvi had all signs of cancer disappear. Meanwhile, half of the treated patients saw their cancer decrease. The approval is also conditional upon further clinical trials that confirm the benefits of Columvi.
Chasing FDA approval
Roche now plans to obtain approval of Columvi from the US Food and Drug Administration (FDA), with a decision expected by July 2023.
T-cell engaging bispecific antibodies have been around for around a decade. One of the pioneers was Amgen’s blinatumomab (Blincyto), which got U.S. FDA market approval in 2014 for the treatment of forms of B cell progenitor acute lymphoblastic leukemia. More recent approvals include Janssen’s teclistamab-cqyv for the treatment of multiple myeloma in 2022.
In late 2022, Lunsumio became the first approved CD20-CD3 bispecific antibody in the US, and was indicated for the treatment of follicular lymphoma. In addition to Columvi, other CD20-CD3 contenders include Regeneron’s odronextamab and AbbVie’s epcoritamab.