Columvi (glofitamab-gxbm)

Six weeks later, while receiving the CD20-directed immunotherapies glofitamab and obinutuzumab, another bone marrow biopsy revealed eradication of the B-ALL and new involvement by pure erythroid leukemia (PEL). This patient's B-ALL lacked an IGH::BCL2 fusion resulting from t(14; 18), suggesting it did not arise through transformation of his prior FL/DLBCL. Instead, the B-ALL was likely caused by his extensive exposure to genotoxic chemotherapy drugs – including alkylating agents – for his preceding lymphomas. The shared cytogenetic and molecular features between this patient's B-ALL and PEL imply they are clonally related.

P2, N=40, Recruiting, The First Affiliated Hospital of Soochow University

P2, N=125, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Recruiting | N=80 --> 125 | Trial primary completion date: Sep 2027 --> Apr 2025

P2, N=30, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P=N/A, N=200, Not yet recruiting, Ruijin Hospital

P2, N=29, Not yet recruiting, Ruijin Hospital

P2, N=53, Recruiting, The First Affiliated Hospital of Xiamen University

P2, N=100, Not yet recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Dec 2031 --> Mar 2032 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Feb 2028 --> May 2028

CD3 × CD20 BsAbs have shown the most promise in clinical development for B-NHL patients, with structural variations affecting their target affinity and potency. This review summarizes the current clinical trials of BsAbs for relapsed/refractory FL, highlighting the approval of some agents, their role in first-line treatment or combination therapies, their toxicity profiles, and the future of this therapeutic approach compared to other immune cell therapies.

Treatment with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone has become the standard of care for newly diagnosed CD20-positive DLBCL with an International Prognostic Index score of 2 to 5, based on its reported efficacy for this indication. In addition, the development of immunotherapy such as anti-CD19-chimeric antigen receptor (CAR)-T therapy and bispecific antibodies such as epcoritamab, mosunetuzumab, and glofitamab has led to a paradigm shift in treatment of relapsed/refractory DLBCL. This review summarizes the evolution of treatment development for DLBCL, as well as the results of the current clinical standard of care and new therapies that are expected to become the standard of care.

P1, N=50, Not yet recruiting, Hoffmann-La Roche

P1, N=121, Recruiting, Hoffmann-La Roche | Trial completion date: Mar 2029 --> Jul 2028 | Trial primary completion date: Mar 2027 --> Jul 2026

P1, N=125, Recruiting, Hoffmann-La Roche | Trial completion date: Jul 2028 --> Mar 2029 | Trial primary completion date: Jul 2026 --> Mar 2027

P1, N=40, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=22, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=45, Not yet recruiting, Ruijin Hospital

P1/2, N=498, Recruiting, Hoffmann-La Roche | Phase classification: P1 --> P1/2 | Trial completion date: Mar 2025 --> Mar 2027 | Trial primary completion date: Mar 2025 --> Mar 2027

P2, N=100, Not yet recruiting, The Lymphoma Academic Research Organisation

P1/2, N=70, Recruiting, Pfizer | Trial completion date: Jun 2028 --> Oct 2028 | Trial primary completion date: Jun 2026 --> Oct 2026

P2, N=30, Not yet recruiting, Samsung Medical Center

P2, N=178, Not yet recruiting, Ryvu Therapeutics SA

Rituximab was the first one approved...Polatuzumab, a CD79b-targeting ADC, is approved as first-line treatment in high-risk patients in combination with chemo-immunotherapy...To date, two BsAbs (glofitamab and epcoritamab) are approved as monotherapy in third-line treatment in DLBCL. Combination strategies with chemotherapy, immunotherapy, and ADCs are currently under investigation with encouraging results in first-line or subsequent lines of treatment. In the following review, we focus on the structure of BsAbs, the mechanism of action, clinical efficacy, and the mechanisms of resistance to BsAbs.

P2, N=80, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting

P1, N=53, Terminated, Hoffmann-La Roche | N=200 --> 53 | Trial completion date: Apr 2025 --> Jul 2024 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Jul 2024; The study was terminated due to sponsor portfolio re-alignment.

P2, N=99, Recruiting, University College, London | Not yet recruiting --> Recruiting | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Jan 2027 --> Jul 2027

P=N/A, N=50, Recruiting, The First Affiliated Hospital of Soochow University

P2, N=40, Recruiting, City of Hope Medical Center | Initiation date: Jun 2024 --> Sep 2024

P=N/A, N=20, Recruiting, Peking Union Medical College Hospital

P2; Not yet recruiting --> Recruiting | Trial completion date: Mar 2028 --> Jul 2028 | Trial primary completion date: Mar 2028 --> Jul 2028

P2, N=46, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1/2, N=70, Recruiting, Pfizer | Trial completion date: Feb 2029 --> Jun 2028 | Trial primary completion date: Feb 2027 --> Jun 2026

Br J Haematol 2024 (Online ahead of print). http://doi.org/10.1111/bjh.19455.

In a field where CD20 × CD3 bispecific antibodies are entering routine clinical use, our experience highlights a potential means of resistance. It illustrates both the need to further characterise mechanisms of CD20 loss, and to pursue clinical trials of novel non-CD20-directed treatments in this cohort.

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Historically, B and T cell (B-T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, and dapirolizumab with variable impact on B cell depletion (BCD), whereas the majority of patients with AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and organ transplantation benefit from targeted BCD with anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab or ofatumumab...In the treatment of cancer, chimeric antigen receptor (CAR) T cell therapy and T cell engagers (TCE) that recruit T cells to induce B cell cytotoxicity have delivered promising results for anti-CD19 CAR T cell therapies, the CD19 TCE blinatumomab and CD20 TCE such as mosunetuzumab, glofitamab or epcoritamab. Limited evidence suggests that anti-CD19 CAR T cell therapy may be effective in managing refractory AID whereas we await evaluation of TCE for use in non-oncological indications. Therefore, here, we discuss the potential mechanistic advantages of novel therapies that rely on T cells as effector cells to disrupt B-T cell collaboration toward overcoming rituximab-resistant AID.

P2, N=40, Recruiting, French Innovative Leukemia Organisation | Not yet recruiting --> Recruiting

P2, N=40, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

P1/2, N=27, Not yet recruiting, OHSU Knight Cancer Institute

P2, N=40, Not yet recruiting, City of Hope Medical Center | Initiation date: Mar 2024 --> Jun 2024

P2, N=99, Not yet recruiting, University College, London | Trial completion date: Jan 2028 --> Jul 2028 | Initiation date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2028 --> Jan 2027

P1/2, N=70, Recruiting, Pfizer | Phase classification: P2 --> P1/2