Lunsumio (mosunetuzumab-axgb)

P2, N=42, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025

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.

P1/2, N=8, Terminated, Hoffmann-La Roche | Completed --> Terminated; Study was terminated due to Sponsor decision.

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=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

P3, N=222, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> Feb 2027 | Trial primary completion date: May 2025 --> Feb 2025

P2, N=345, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting

P2; N=31; Not yet recruiting; Sponsor:Medical College of Wisconsin

P1/2, N=187, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting

P2, N=35, Not yet recruiting, Izidore Lossos, MD

P2, N=36, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=41, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2027 --> Mar 2028

P2, N=20, Recruiting, University of Washington | Not yet recruiting --> Recruiting

P1/2, N=40, Recruiting, OHSU Knight Cancer Institute | Not yet recruiting --> Recruiting

P2, N=56, Not yet recruiting, Fondazione Italiana Linfomi - ETS

P2, N=41, Not yet recruiting, City of Hope Medical Center

Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively. This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.

P2, N=20, Not yet recruiting, University of Washington

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P1/2, N=188, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Aug 2023 --> Aug 2025

Prior to Mosun treatment, ~50% of patients had residual levels of anti-CD20 drugs (e.g., rituximab or obinutuzumab) from prior treatment. The 60 mg loading doses increased Mosun CD20 RO% in Cycle 1, providing efficacious exposures in the presence of the competing anti-CD20 drugs. PopPK model simulations, investigating Mosun dose delays, informed treatment resumption protocols to ensure CRS mitigation.

P1/2, N=187, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Feb 2024 --> Nov 2025

P1, N=30, Recruiting, National Cancer Institute (NCI) | Initiation date: Sep 2024 --> May 2024

P1, N=15, Recruiting, Washington University School of Medicine | Trial completion date: Jun 2027 --> Jun 2029

P3, N=790, Recruiting, The Lymphoma Academic Research Organisation | Not yet recruiting --> Recruiting

P1, N=50, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not 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.

P1/2, N=187, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Nov 2027 --> Feb 2024

P2, N=396, Recruiting, SWOG Cancer Research Network | Trial primary completion date: Dec 2024 --> Dec 2025

P3, N=600, Not yet recruiting, National Cancer Institute (NCI)

P2, N=42, Recruiting, University of Washington | Trial completion date: Aug 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Dec 2025

P1/2, N=422, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Oct 2024 --> Jan 2024

P1/2, N=8, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | N=118 --> 8 | Trial completion date: Dec 2023 --> Jul 2023 | Trial primary completion date: Dec 2023 --> Jul 2023

P3, N=790, Not yet recruiting, The Lymphoma Academic Research Organisation

P2, N=70, Recruiting, National Cancer Institute (NCI) | Initiation date: Jul 2024 --> Jan 2024

P1/2, N=836, Active, not recruiting, Genentech, Inc. | Trial completion date: Nov 2023 --> Nov 2025 | Trial primary completion date: Nov 2023 --> Nov 2025

P1/2, N=40, Not yet recruiting, OHSU Knight Cancer Institute

P1, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: May 2025 --> Dec 2025 | Initiation date: Dec 2023 --> Sep 2024 | Trial primary completion date: May 2025 --> Dec 2025

P1/2, N=188, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting

P1, N=200, Recruiting, ADC Therapeutics S.A. | Phase classification: P1b --> P1

P1, N=137, Recruiting, Hoffmann-La Roche | N=56 --> 137 | Trial completion date: Jul 2027 --> Oct 2029 | Trial primary completion date: Feb 2026 --> May 2027