Lunsumio (mosunetuzumab-axgb) / Roche, Biogen - LARVOL DELTA

Lunsumio: “Extension application to introduce a new pharmaceutical form (solution for injection) associated with two new strengths (5 mg and 45 mg) and new route of administration (subcutaneous use).” (European Medicines Agency) - CHMP Final Minutes of the meeting on 22 - 25 Apr 2025: “The committee discussed the issues identified in this application, relating to quality and clinical aspects”

CHMP • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Bispecific Antibodies-A New Hope for Patients with Diffuse Large B-Cell Lymphoma. (PubMed, J Clin Med) - "The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin's lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring."

Journal • Review • B Cell Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Therapy Sequencing in Relapsed/Refractory MCL (ICML 2025) - P1, P1/2, P2, P3 | "Although a direct comparison between them has only been performed for ibrutinib and temsirolimus [23], covalent BTK inhibitor (cBTKi) single agent therapy has been consolidated as the standard of care after first-line CIT. Moreover, to address cBTKi failure, two anti-CD19 CAR-T cell therapy products, brexucabtagene autoleucel [20, 21] and lisocabtagene maraleucel [22], and the first noncovalent BTKi, pirtobrutinib [19], have recently been approved...Liso-cel only FDA approved; CIT, chemoimmunotherapy options include BR, R-BAC, R-CHOP, R-DHAP or R-DHAOx, R-GEMOx, paliative options (avoid bendamustine pre-CART apheresis); pirtobrutinib, available after cBTKi failure in second-line (EMA) but third-line (FDA); RM, rituximab maintenance...Orelabrutinib [18] is licensed only in China...Of note, both acalabrutinib and zanubrutinib induce lower rates of atrial fibrillation, hypertension, and bleeding compared to ibrutinib in randomized studies..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • PLCG2 • TP53

Clinical representativeness of pivotal trials for T-cell engagers in relapsed/refractory follicular lymphoma. (PubMed, Future Oncol) - "The epcoritamab trial enrolled more broadly and was more representative of typical R/R FL patients than the mosunetuzumab, tisa-cel, and axi-cel trials. Differences in patient characteristics should be considered when evaluating the comparative benefits of T-cell engagers in R/R FL after ≥ 2 systemic therapies."

Journal • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Bispecific Antibodies in Hematologic Malignancies: Attacking the Frontline. (PubMed, BioDrugs) - "Since blinatumomab's approval as the first bispecific antibody (BsAb) in cancer therapy, these immunomodulatory agents have achieved substantial success in lymphoid malignancies...In lymphoma, epcoritamab, glofitamab, and mosunetuzumab show proof-of-principle for complete remission (CR) without chemotherapy or cell-based treatment...In MM, teclistamab, talquetamab, and elranatamab achieve impressive CR rates in the relapsed setting and similarly, are being investigated in earlier line combinations and in precursor entities such as smoldering myeloma and monoclonal gammopathy of undetermined significance (MGUS). With a unique mechanism of action and continued testing in earlier lines, BsAbs are poised to be among the winners in the race to the frontline treatment of hematologic malignancies."

Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Monoclonal Gammopathy • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Smoldering Multiple Myeloma

FIL_MOZART: Study With Mosunetuzumab and Zanubrutinib in R/R Follicular Lymphoma Patients (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: Fondazione Italiana Linfomi - ETS | Not yet recruiting ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

CO41942: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide (+Len), and the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Participants With Follicular Lymphoma (clinicaltrials.gov) - P1/2 | N=237 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • CD20 • CD4

Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma. (PubMed, Blood Adv) - P1/2, P2 | "Epcoritamab also exhibited clinically relevant, numerically higher ORRs and demonstrated improved safety for CRS (grade ≥3) and ICANS vs mosunetuzumab or odronextamab. NCT03625037; NCT02500407; NCT03888105."

Journal • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Lunsumio SC: Regulatory approval in EU for 3L + follicular lymphoma in 2025 (Roche) - H1 2025 Results

EMA approval • Follicular Lymphoma • Hematological Malignancies • Oncology

Lunsumio + Polivy: Regulatory approval in Japan for 2L+ DLBCL in 2025 (Roche) - H1 2025 Results

Japan approval • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

Lunsumio: Regulatory submissions in US/EU in combination with lenalidomide for 2L follicular lymphoma in 2026 (Roche) - H1 2025 Results

EMA filing • FDA filing • Follicular Lymphoma • Hematological Malignancies • Oncology

Mosunetuzumab and Polatuzumab Vedotin With Split-Dose CHP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: Medical College of Wisconsin | Initiation date: Jun 2025 ➔ Oct 2025

Trial initiation date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Roche withdraws promising cancer drug (Bluewin) - "The pharmaceutical company Roche has decided to withdraw the cancer drug Lunsumio from the market after price negotiations with the Federal Office of Public Health (FOPH) failed. The Tages-Anzeiger newspaper reports that the drug is considered a beacon of hope for patients with advanced lymph node cancer...According to the Tages-Anzeiger, Lunsumio was originally launched via an 'early access' procedure, which enabled reimbursement despite incomplete clinical data. However, Roche had not provided the required data and nevertheless demanded a higher price. The FOPH rejected this because it did not want to make any exceptions...Roche says that the reimbursement conditions are not acceptable to them, even in the case of individual reimbursement...Roche argues that the development costs for drugs are high - on average 5.5 billion Swiss francs....Roche is offering the drug free of charge in cases of hardship via a voluntary access system."

Reimbursement • Lymphoma

Fixed duration subcutaneous (SC) mosunetuzumab (Mosun) in patients with previously untreated high-tumor burden follicular lymphoma (FL): Interim results from the phase II MorningSun study. (BASCO-MN 2025) - No abstract available

Clinical • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Marginal Zone Lymphoma: Treatment Update With a Focus on Systemic Approaches (ICML 2025) - P2, P3 | "Amongst 454 enrolled patients and with a median follow up time of over 7 years, the combination of rituximab plus chlorambucil had superior EFS (5-year EFS 68% vs. 50%) but no difference in overall survival which was excellent at 90% [17]. Other approaches added bendamustine to rituximab...Initial trials with the first-in-class covalent BTKi inhibitor, ibrutinib, were promising...The second generation covalent BTKi zanubrutinib and acalabrutinib have also been evaluated in RR MZL, with zanubrutinib receiving regulatory approval in the United States and the European Union...Unfortunately, the first-in-class PI3Kδ inhibitor, idelalisib, was associated with significant toxicities, including infection and immune-mediated complications...In MZL, there is a recent publication of parsaclisib with intriguing findings [29]...ZUMA-5 is a multicenter Phase 2 trial of axicabtegene ciloleucel (axi-cel) conducted in patients with both FL and MZL [30]...Several CD20xCD3 BsAbs,..."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hairy Cell Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Splenic Marginal Zone Lymphoma • CD5 • CRBN • MME • MYD88 • PIK3CD

Follicular Lymphoma: Current Therapeutic Landscape and Future Prospects (ICML 2025) - P3 | "The ability of maintenance rituximab, obinutuzumab induction, or bendamustine-based induction to lower early progression rates without affecting OS or HT rate [10, 12, 18] suggests that not all POD24 cases are equal, with a subset remaining resistant to current treatments...Since 2021, three CAR-T constructs—axicabtagene-ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)—and three CD3 × CD20 BsAbs—mosunetuzumab, epcoritamab, and odronextamab—have gained regulatory approval in Europe and/or US as options for third line and later...Loncastuximab tesirine (CD19-directed ADC) shows promising activity in 2L+ R/R FL (CR 67%, manageable toxicity in a small Phase 2 cohort) [40]. Adding tafasitamab, an anti-CD19 antibody, to R2 in R/R FL patients improved PFS by 57% in the inMIND trial after a median follow-up of 14 months [41]...However, the ROSEWOOD trial showed obinutuzumab-zanubrutinib was superior to Obinutuzumab alone..."

IO biomarker • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • EZH2 • IGH

Mosunetuzumab for CLL MRD Clearance (clinicaltrials.gov) - P1/2 | N=40 | Not yet recruiting | Sponsor: Inhye Ahn

Minimal residual disease • New P1/2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Mosunetuzumab-associated fatal HHV-6 encephalitis in a patient with follicular lymphoma. (PubMed, J Oncol Pharm Pract) - "Following positive PCR testing for HHV-6, IV ganciclovir was commenced...This is the first instance of HHV-6 encephalitis associated with mosunetuzumab. The case underscores the importance of early CSF analysis and neuroimaging in patients with encephalopathy receiving T-cell-engaging therapies."

Journal • CNS Disorders • Epstein-Barr Virus Infections • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • Transplantation

CTEP TRIAL 10590, NORM: NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA PATIENTS TREATED IN A RANDOMIZED PHASE II TRIAL WITH EITHER RITUXIMAB OR MOSUNETUZUMAB (ICML 2025) - P2 | "The expected sample size is 56.1 under the null hypothesis and 61.9 under the alternative hypothesis. The study is open for accrual in the US and Canada since 2024."

Clinical • P2 data • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Lymphoma • Nodular Lymphocyte Predominant Hodgkin Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

T-Cell Redirecting Strategies in Large B-Cell Lymphoma and Follicular Lymphoma (ICML 2025) - "The randomized STARGLO trial compared the combination of glofitamab with gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx, meeting its primary endpoint of OS in favor of the experimental arm (HR 0.62 [95% CI 0.43–0.88])...Other treatment options to consider in this R/R patient population are tafasitamab/lenalidomide [107], loncastuximab tesirine [108] and rituximab-bendamustine-polatuzumab [109], amongst others...Three CAR-T constructs are available based on Phase 2, single-arm trials, namely ZUMA-5 (axi-cel), ELARA (tisa-cel), and TRANSCEND-FL (liso-cel)...Mosunetuzumab, epcoritamab and odronextamab received regulatory approval (U.S...She started treatment with a bispecific antibody, aiming to carry out her first imaging assessment after three cycles. Permission to Reproduce Material From Other Sources The author has nothing to report."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD19

MARSUN, A PHASE III, MULTICENTER, OPEN LABEL, RANDOMIZED STUDY INVESTIGATING MOSUNETUZUMAB-LENALIDOMIDE VERSUS INVESTIGATOR CHOICES IN R/R MARGINAL ZONE LYMPHOMAS (ICML 2025) - "Previous treatment lines must include at least one systemic line with a monoclonal antibody targeting CD20 (at least 2 cycles) with or without chemotherapy (CHOP, bendamustine, CVP, chlorambucil) or targeted treatment...This phase is followed by a randomized 1:1 phase to receive M-len or investigator choice (125 patients per arm) (R-Len (12 cycles) and R-chemotherapy (R-Bendamustine or R-CHOP followed by a 6 months maintenance)... The safety run is now closed and the randomized phase of the MARSUN clinical trial is ongoing."

Clinical • P3 data • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Oncology

MOSUNETUZUMAB FOR EARLY RELAPSE OF FOLLICULAR LYMPHOMA IN THE NORDIC COUNTRIES (MERLIN) (ICML 2025) - "Research funding declaration: MERLIN is an academic clinical trial with funding from Roche Introduction: Standard first line treatment for patients with symptomatic follicular lymphoma (FL) is anti-CD20 antibody treatment, for example, with rituximab (R) alone or combined with chemotherapy or lenalidomide. The samples will be subject to single cell sequencing analyses to identify immunological determinants of response versus resistance to mosunetuzumab. Cell free DNA from blood is collected at several time points during the trial and will be subject to next generation sequencing and used for the assessment of minimal residual disease."

Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

CO41942: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide (+Len), and the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Participants With Follicular Lymphoma (clinicaltrials.gov) - P1/2 | N=237 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • CD20 • CD4

Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Update on Biology and Treatment (ICML 2025) - P2 | "A single-center analysis included 27 NLPB/HL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) either alone or followed by consolidation RT...A different analysis investigated 20 patients who had treatment with BR (bendamustine, rituximab)...At 26 months, the 2-year PFS estimate among 28 patients with relapsed NLPB/HL treated with eight weekly doses of ofatumumab was 80%...Novel approaches that might play a role in the future treatment of NLPB/HL include chimeric antigen receptor T-cell therapy and bispecific antibodies. A study investigating the CD20xCD3 bispecific antibody mosunetuzumab in NLPB/HL (NCT05886036) is currently open for recruitment in North America [55]."

IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Nodular Lymphocyte Predominant Hodgkin Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Histiocyte Rich Large B Cell Lymphoma • BCL6 • CARD11 • CD163 • CD4 • CD79A • CD8 • DUSP2 • IGH • IRF4 • JAK2 • JUNB • MME • NOTCH2 • PAX5 • PD-1 • PD-L1 • SOCS1 • STAT6 • TET2 • TNFRSF8

NEW TRENDS IN LYMPHOMA TREATMENT IN WESTERN COUNTRIES (ICML 2025) - "Second-line CAR T-cells have shown a remarkable superiority when compared to autologous stem cell transplant (ASCT) in DLBCL patients failing frontline approach (not achieving a complete response or relapsing within one year since the end of induction), which concretizes in a median event-free survival gain of at least 8 months for both axicabtagene ciloleucel and lisocabtagene maraleucel...Longer follow-up is also available for glofitamab and epcoritamab in DLBCL: for both it can be demonstrated that a 55%–64% of patients are still in CR at 24 months, and that among patients who obtained a CR at the end or during treatment (depending on the agent used) the 2-year overall survival largely exceeds 70%. Mosunetuzumab in follicular lymphoma has yielded a progression-free survival rate of 38% at 4 years, with no significant differences observed between patients progressing within 24 months since frontline treatment (POD24) and non-POD24 ones. The TRIANGLE trial has shown..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • JAK1