Mosunetuzumab
- Generic Name
- Mosunetuzumab
- Brand Names
- Lunsumio
- Drug Type
- Biotech
- CAS Number
- 1905409-39-3
- Unique Ingredient Identifier
- LDJ89SS0YG
- Background
Mosunetuzumab is a humanized anti-CD20/CD3 bispecific antibody. It can recognize and bind two different targets simultaneously, CD20 on cancer B-cells and CD3 on T-cells, allowing it to redirect T-cell cytotoxic activity to cancer cells. The standard of care for patients with B-cell lymphoma includes an anti-CD20 monoclonal antibody, such as rituximab, in combination with chemotherapy. However, patients with certain types of B-cell lymphoma, such as follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) or aggressive B-cell lymphoma, have a high probability of relapse or recurrence after treatment. Mosunetuzumab has the potential to circumvent resistance to rituximab in patients with follicular lymphoma, and unlike CAR-T therapies such as axicabtagene ciloleucel and tisagenlecleucel, it is an “off-the-shelf” alternative, readily available to patients. In June 2022, the European Medicines Agency approved mosunetuzumab for the treatment of adult patients with relapsed or refractory (R/R) FL who have received at least two prior systemic therapies. In January 2023, the use of mosunetuzumab was approved by the FDA under accelerated approval based on response rate.
- Indication
Mosunetuzumab as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
- Associated Conditions
- Relapsed or Refractory Follicular Lymphoma
Genentech Partners with Repertoire Immune Medicines in $765M Deal for Autoimmune Disease Drug Discovery
• Genentech has entered a partnership with Repertoire Immune Medicines, providing $35 million upfront and up to $730 million in milestone payments to develop T cell-targeting therapies for an undisclosed autoimmune disorder.
• Repertoire's DECODE platform, which maps the immune synapse between T cells and antigen-presenting cells, will be central to the collaboration, with Repertoire leading early discovery and Genentech handling later development.
• This marks Repertoire's second major pharmaceutical partnership following a strategic pivot from personalized cell therapies, having previously secured a deal with Bristol Myers Squibb worth up to $1.8 billion for autoimmune disease vaccines.
FDA Grants Priority Review to Roche's Lunsumio for Follicular Lymphoma Treatment
• The FDA has granted priority review to Lunsumio, Roche's novel T-cell engager targeting CD20 and CD3, with a decision expected by December 29 for relapsed/refractory follicular lymphoma treatment.
• Clinical trials demonstrated impressive efficacy with an 80% overall response rate and 60% complete responses in third-line or later therapy, comparable to existing CAR-T cell therapies.
• As an off-the-shelf outpatient treatment, Lunsumio offers significant advantages over CAR-T therapies by eliminating manufacturing delays and the need for hospitalization.
Tambiciclib-Zanubrutinib Combo Shows 67% Response Rate in Relapsed/Refractory DLBCL Trial
• Phase 2a trial demonstrates promising 67% overall response rate for tambiciclib plus zanubrutinib combination in relapsed/refractory DLBCL patients, including one complete response.
• The combination therapy showed particularly strong efficacy in ABC DLBCL subtype patients, achieving an 83% disease control rate with 4 responses and 1 stable disease out of 6 patients.
• Safety profile reveals grade 3 or higher adverse effects in 55.6% of patients, while genetic analysis indicates efficacy independent of MYD88 or CD79B mutations.
Lunsumio Shows Durable 3-Year Remission in Follicular Lymphoma, Setting New Benchmark for Bispecific Antibodies
• Lunsumio demonstrated a 60% complete response rate and 77.8% objective response rate in relapsed/refractory follicular lymphoma patients over a 37.4-month follow-up period.
• The bispecific antibody therapy achieved an estimated 82.4% three-year overall survival rate with just eight cycles of fixed-duration treatment, maintaining durable remission in most complete responders.
• As Korea's first GIFT-approved drug, Lunsumio's long-term data could potentially break the reimbursement barrier for bispecific antibodies, offering advantages of outpatient administration and minimal pretreatment requirements.
Gazyva Shows Significant Improvement in Lupus Nephritis Treatment: Phase III REGENCY Trial Results
• Genentech's Phase III REGENCY trial demonstrates that Gazyva plus standard therapy achieved 46.4% complete renal response in lupus nephritis patients compared to 33.1% with standard therapy alone.
• The study, published in NEJM, showed clinically meaningful improvements in complement levels and reductions in anti-dsDNA markers, indicating reduced disease activity and inflammation.
• Results were consistent across all patient subgroups, including those with Class IV lupus nephritis and higher baseline proteinuria levels, while maintaining Gazyva's established safety profile.
Dual Targeting PD-L1 and 4-1BB Overcomes Lenalidomide Resistance in Follicular Lymphoma
• A phase 2 trial identified dendritic cells (DCs) as critical in follicular lymphoma (FL) progression under rituximab plus lenalidomide (R2) treatment, highlighting the need for new strategies.
• PU.1, a transcription factor, mediates lenalidomide resistance by modulating PD-L1 and 4-1BB interaction between lymphoma cells and DCs, impacting anti-tumor immunity.
• Dual targeting of PD-L1 and 4-1BB with a bispecific antibody counteracts PU.1-mediated alterations in DCs, enhancing lymphoma cell autophagy and anti-tumor activity in vitro and in vivo.
• The study suggests that combining immune checkpoint modulation with lenalidomide could be a promising chemo-free immunotherapy approach for overcoming resistance in FL treatment.
J&J's Carvykti Shows Promise in Earlier Myeloma Treatment
• The CARTITUDE-4 study indicates that Carvykti (ciltacabtagene autoleucel) significantly improves progression-free survival in multiple myeloma patients with 1-3 prior lines of therapy.
• Carvykti, a BCMA-directed CAR-T therapy, may soon be used earlier in the treatment pathway, potentially leapfrogging Bristol-Myers Squibb's Abecma.
• The study compared Carvykti to standard three-drug regimens, showing a significant benefit that led to unblinding of the trial.
• Expansion of Carvykti's use is a key component of J&J's strategy in multiple myeloma, alongside other therapies like Darzalex and bispecific antibodies.
Japan Approves Lunsumio (mosunetuzumab) for Relapsed/Refractory Follicular Lymphoma
• Chugai Pharmaceutical's Lunsumio (mosunetuzumab) has received approval in Japan for treating relapsed or refractory follicular lymphoma (R/R FL).
• Lunsumio, a CD20/CD3 bispecific antibody, offers a novel monotherapy approach with potential for durable remission in patients who have failed two or more prior therapies.
• Approval was based on the FLMOON-1 study in Japanese patients and an overseas Phase I/II trial, demonstrating complete response rates of 68.4% and 57.8%, respectively.
• The treatment duration is tailored to patient response, aiming to reduce the overall burden of treatment and improve outcomes for R/R FL patients.
CD20 Bispecific Antibodies Show Promise in Lymphoma Treatment at ASH
Recent findings at the American Society of Haematology meeting highlight the potential of CD20 bispecific antibodies in treating lymphoma, with Roche's Lunsumio leading the way. Regeneron and AbbVie also presented promising data on their candidates, odronextamab and epcoritamab, respectively, showcasing significant efficacy in clinical trials. These developments mark a significant step forward in offering alternatives to CAR-T therapies, with a focus on improving patient outcomes in relapsed or refractory lymphoma cases.
Monjuvi Combination Shows Promise in Relapsed/Refractory Follicular Lymphoma
• The combination of Monjuvi, Revlimid, and Rituxan significantly reduces the risk of disease progression or death in relapsed/refractory follicular lymphoma patients.
• The inMIND phase 3 trial demonstrated a median progression-free survival of 22.4 months with the Monjuvi combination, compared to 13.9 months with Revlimid and Rituxan alone.
• The Monjuvi combination showed improved objective response rates and duration of response compared to the Revlimid and Rituxan doublet.
• Incyte plans to file for FDA approval of Monjuvi combination for relapsed/refractory follicular lymphoma based on the inMIND trial results.
Regeneron's Ordspono Shows Promise in Relapsed/Refractory Marginal Zone Lymphoma
• Ordspono (odronextamab) demonstrates a 77.1% objective response rate in relapsed/refractory marginal zone lymphoma (MZL) patients who have undergone second-line or later systemic therapy.
• The Phase II ELM-2 trial highlights a manageable safety profile for Ordspono, with cytokine release syndrome (CRS) limited to grade 1–2 severity through step-up dosing.
• Despite promising efficacy, regulatory challenges persist as the FDA rejected Regeneron’s application, requiring a clear timeline for confirmatory trials before resubmission.
• Ordspono faces competition from other bispecific T-cell engager therapies, necessitating robust comparisons to standard-of-care treatments to establish its market niche.
Roche's Bispecific Antibodies Columvi and Lunsumio Show Durable Remissions in Lymphoma Patients
• Long-term data confirm that fixed-duration Columvi and Lunsumio achieve lasting remissions beyond treatment, potentially reducing travel burden due to less frequent dosing.
• Subcutaneous administration of Lunsumio demonstrates non-inferiority to intravenous treatment with a consistent safety profile, offering a shorter administration time.
• Columvi combined with Polivy shows high response rates in relapsed/refractory large B-cell lymphoma, including those previously treated with CAR T-cell therapy.
• These results support Roche's efforts to provide diverse treatment options for lymphoma patients, improving treatment standards and patient experience.
AstraZeneca's AZD0486 Shows Promise in Relapsed/Refractory Follicular Lymphoma
• AstraZeneca presented promising interim results for AZD0486, a novel bispecific T-cell engager, in relapsed/refractory follicular lymphoma (r/r FL) at ASH 2024.
• In patients receiving doses of 2.4 mg or more, AZD0486 achieved a 96% overall response rate and an 85% complete response, comparing favorably to existing therapies.
• AZD0486 targets CD19 on cancerous cells and CD3 on T-cells, inducing cell lysis and T-cell proliferation with manageable cytokine release syndrome.
• A phase II trial of AZD0486 in r/r FL is underway, potentially leading to a first-in-class approval for a CD19xCD3 BiTE in this indication.
Polivy Combination Therapy Shows Sustained Benefit in Aggressive Lymphoma
• Five-year follow-up data from the POLARIX study shows a positive trend in overall survival for patients with previously untreated diffuse large B-cell lymphoma (DLBCL) treated with Polivy in combination with R-CHP.
• Patients receiving Polivy with R-CHP required approximately 25% fewer subsequent treatments like radiation or CAR-T cell therapy, potentially reducing healthcare burdens.
• The progression-free and disease-free survival benefits of Polivy plus R-CHP were maintained, reinforcing its potential for durable remissions in DLBCL.
• The safety profile of the Polivy combination remained consistent, with no new safety signals, supporting its favorable benefit-risk profile.
FDA Accepts sBLA for Glofitamab Plus Chemotherapy in Relapsed/Refractory DLBCL
• The FDA has accepted Roche's sBLA for glofitamab combined with gemcitabine and oxaliplatin (GemOx) for relapsed/refractory DLBCL patients ineligible for autologous stem cell transplant.
• The sBLA is based on the phase 3 STARGLO trial, which demonstrated a statistically significant and clinically meaningful improvement in overall survival compared to rituximab plus GemOx.
• The FDA is expected to make a decision on the approval of glofitamab in combination with GemOx by July 20, 2025, offering a potential new treatment option.
• The safety profile of glofitamab plus GemOx was consistent with the known safety profiles of the individual agents, with cytokine release syndrome being a common adverse event.
Roche Highlights Advances in Blood Disorder Treatments at ASH 2024
• Roche will present over 40 abstracts at the 66th ASH meeting, showcasing advancements in lymphoma and other blood disorders, reinforcing their commitment to hematology.
• Five-year data from the POLARIX study shows a positive trend in overall survival for first-line diffuse large B-cell lymphoma (DLBCL) patients treated with Polivy in combination with R-CHP.
• Extended follow-up data from studies of Lunsumio and Columvi demonstrate long-lasting remissions and immune system recovery in follicular lymphoma and DLBCL, respectively.
• Data on subcutaneous Lunsumio shows high response rates and low cytokine release syndrome, potentially improving patient experience with shorter administration times.
Genentech Presents Promising Blood Disorder Data at ASH 2024
• Genentech presented data at ASH 2024 highlighting advancements in lymphoma treatment with Polivy, Lunsumio, and Columvi, showcasing durable remissions and overall survival benefits.
• Five-year data from the Phase III POLARIX study showed a positive trend in overall survival for first-line diffuse large B-cell lymphoma (DLBCL) patients treated with Polivy combination therapy.
• Extended follow-up data from studies of Lunsumio and Columvi demonstrated long-lasting remissions and immune system recovery, supporting their use as fixed-duration bispecific antibodies.
• New data on subcutaneous Lunsumio showed high response rates and low cytokine release syndrome, potentially improving patient experience with shorter administration times.
Genentech Highlights Long-Term Data Across Hematology Portfolio at ASH 2024
• Genentech will present over 40 abstracts at the ASH Annual Meeting, showcasing advancements in lymphoma and other blood disorders.
• Five-year data from the POLARIX study shows Polivy, combined with R-CHP, has a positive trend in overall survival for DLBCL patients.
• Extended follow-up data of Lunsumio and Columvi demonstrate long-lasting remissions and immune system recovery in follicular lymphoma and DLBCL.
• Subcutaneous Lunsumio shows high response rates and low CRS rates, potentially improving patient experience with shorter administration times.
Genentech Presents Encouraging Long-Term Data for Lymphoma and Hemophilia Treatments
• Genentech's Polivy, in combination with R-CHP, demonstrates sustained benefits in diffuse large B-cell lymphoma (DLBCL) after five years.
• Lunsumio shows high durable response rates and a manageable safety profile in relapsed/refractory follicular lymphoma, even after multiple prior therapies.
• Columvi maintains durable responses in relapsed/refractory large B-cell lymphoma, including high-grade B-cell lymphoma, with extended follow-up.
• Hemlibra demonstrates effective bleed control in infants with hemophilia A, from birth to 12 months, according to exploratory analysis of the HAVEN 7 study.
Intermountain Health's St. Vincent Reaches Milestone with 800th Clinical Trial Patient
• Intermountain Health's St. Vincent Regional Hospital enrolled its 800th patient in a clinical trial, marking a significant milestone since the program's inception in 2015.
• The hospital's clinical research team has grown substantially, attracting pharmaceutical companies with faster clinical trial start-up times compared to larger academic centers.
• A patient with stage 4 lymphoma achieved remission through a cutting-edge immunotherapy treatment (Lunsumio) as part of a clinical trial at St. Vincent.
• The expansion of clinical trials in Billings offers Montana residents access to advanced medical treatments, reducing the need to travel long distances for care.
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