Columvi (glofitamab-gxbm)

P2, N=41, Active, not recruiting, Jennifer Crombie, MD | Recruiting --> Active, not recruiting

P2, N=76, Active, not recruiting, Seoul National University Hospital | Recruiting --> Active, not recruiting

P1/2, N=65, Recruiting, Hoffmann-La Roche | Trial primary completion date: Oct 2027 --> Mar 2027

P2, N=178, Recruiting, Ryvu Therapeutics SA | Not yet recruiting --> Recruiting

In this study, we further developed our protocol MCCS-Docker for protein-protein interactions and applied it to investigate the structural intricacies of CD3 interactions with therapeutic antibodies such as OKT3, UCHT1, Mosunetuzumab, Odronextumab, Glofitamab, and Epcoritamab using computational modeling techniques. Molecular dynamics simulations validated the stability of these interactions over time, confirming the reliability of the binding poses generated from docking studies. Overall, our study offered a novel method to predict critical residues in protein-protein interactions and enhanced the understanding of the structural determinants governing BsAb interactions with target proteins, offering valuable insights for designing and optimizing immunotherapeutic agents for NHL and related hematologic malignancies.

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

P1/2, N=860, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

Patients will receive obinutuzumab 2000 mg IV on C1D1-2, followed by glofitamab step-up dosing of 2.5 mg IV on C1D8, 10 mg on C1D15, and 30 mg on day 1 of C2-12 (21-day cycles). In the current trial we evaluate a regimen which we anticipate will be tolerable and highly active in R/R MCL, with the potential for MRD-guided limited-duration therapy. The trial is currently open for enrollment at UCSF and is expected to open at multiple centers through the University of California Hematologic Malignancies Consortium.

P2, N=30, Suspended, C. Babis Andreadis | N=50 --> 30 | Recruiting --> Suspended

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

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

All pts received obinutuzumab pretreatment (1000mg or 2000mg) on Cycle (C) 1 Day (D) 1. Conclusions : Glofitamab induces high response rates in pts with heavily pretreated R/R MCL, including those who have clinical and/or histological features associated with poor prognosis. Clinical and molecular remissions are achieved early in the course of treatment, with durable responses lasting beyond the length of the treatment.

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