Glofitamab
- Generic Name
- Glofitamab
- Brand Names
- Columvi
- Drug Type
- Biotech
- CAS Number
- 2229047-91-8
- Unique Ingredient Identifier
- 06P3KLK2J8
- Background
Glofitamab is a full-length bispecific monoclonal antibody with affinity for both CD20 and CD3 surface antigens found on B- and T-cells, respectively. It has a 2:1 configuration, with bivalency towards CD20 and monovalency towards CD3, and works by recruiting T-cells directly to the surface of cancerous B-cells.
Glofitamab was approved by Health Canada in March 2023 for the treatment of certain patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), becoming the first CD20/CD3 bispecific monoclonal antibody approved for DLBCL. The most common type of non-Hodgkin lymphoma, DLBCL is relatively sensitive to chemotherapy and generally responsive to first-line treatment regimens like CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) - despite this, as many as 40% of patients will experience relapsed or refractory disease. In the context of relapsed or refractory DLBCL, glofitamab provides an alternative treatment option for patients having failed other systemic therapies or for whom targeted therapies - such as CAR-T cell therapy - are inappropriate.
In June 2023, the FDA approved the use of glofitamab for the treatment of patients with relapsed or refractory DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy under accelerated approval based on response rate and durability of response.
Glofitamab was granted conditional marketing authorization in July 2023 by the EMA for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. This approval is based on the positive results obtained from the phase I/II NP30179 study, where 35.2% of study participants achieved a complete response.
- Indication
Glofitamab is indicated in Canada for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma (PMBCL), who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR-T cell therapy or have previously received CAR-T cell therapy. This indication has been authorized pending the results of trials designed to verify glofitamab's clinical benefit.
The FDA approved glofitamab under accelerated approval for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.
Glofitamab was also approved by the EMA to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy.
- Associated Conditions
- Diffuse Large B-Cell Lymphoma (DLBCL), Large B Cell Lymphoma, Primary Mediastinal (Thymic) Large B Cell Lymphoma (PMBCL), Refractory Diffuse Large B Cell Lymphoma (DLBCL), Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Relapsed Diffuse Large B-cell Lymphoma (DLBCL), Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
FDA Advisory Committee Votes 6-2 in Favor of Daratumumab for High-Risk Smoldering Multiple Myeloma
• The FDA's Oncologic Drug Advisory Committee (ODAC) voted 6-2 that daratumumab (Darzalex Faspro) demonstrates a favorable benefit-risk profile for patients with high-risk smoldering multiple myeloma, potentially offering the first approved therapy for this precursor condition.
• The phase 3 AQUILA trial showed daratumumab significantly delayed progression to active multiple myeloma with a 51% reduction in risk of progression or death compared to active monitoring, with 5-year PFS rates of 63.1% versus 40.8%.
• Committee members expressed concerns about risk classification accuracy and potential overtreatment, but ultimately determined the benefits outweighed risks for this malignant condition that has an 80% five-year progression risk to symptomatic multiple myeloma.
FDA Advisory Committee Rejects New Indications for Genentech's Columvi and Pfizer's Talzenna Combination
• The FDA's Oncologic Drugs Advisory Committee voted 8-1 against approving Genentech's Columvi for a new indication, citing concerns about the pivotal trial's applicability to US patients.
• In a separate decision, the same committee unanimously rejected (8-0) Pfizer's application for Talzenna in combination with Xtandi for first-line treatment in adults with prostate cancer.
• These negative recommendations highlight the FDA's increasing scrutiny of oncology drug applications and may signal stricter requirements for clinical trial design and population representation.
FDA Advisory Committee Rejects Genentech's Columvi Expansion for Transplant-Ineligible DLBCL Patients
• The FDA's Oncologic Drugs Advisory Committee voted 8-1 against expanding Genentech's bispecific antibody Columvi for transplant-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma.
• Committee members expressed concerns about the applicability of the Phase III STARGLO study data to the U.S. population, as half of the participants were Asian patients with only 25 enrolled from North America.
• Columvi, which targets CD20 and CD3 proteins, was initially approved in June 2023 for DLBCL patients who had undergone at least two prior lines of systemic therapy.
Glofitamab-GemOx Shows Survival Benefit in Phase 3 STARGLO Trial for R/R DLBCL, But FDA Advisory Committee Questions US Applicability
• The phase 3 STARGLO trial demonstrated that glofitamab combined with gemcitabine and oxaliplatin nearly doubled median overall survival to 25.5 months compared with 12.9 months for rituximab-GemOx in transplant-ineligible R/R DLBCL patients.
• Despite showing a 41% reduction in death risk and 63% reduction in disease progression, the FDA's Oncologic Drugs Advisory Committee voted 8-to-1 against the applicability of the trial data to US patients, citing regional outcome differences.
• Glofitamab, a CD20xCD3 bispecific antibody, is currently approved in over 30 countries and has accelerated approval in the US, with an FDA decision on full approval expected by July 20, 2025.
FDA Advisory Committee Discusses Columvi Combination for Relapsed or Refractory DLBCL
• Genentech's Columvi (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin demonstrated a 41% reduction in risk of death for patients with relapsed or refractory diffuse large B-cell lymphoma in the Phase III STARGLO study.
• The FDA Oncologic Drugs Advisory Committee met to discuss the supplemental Biologics License Application for this combination therapy, focusing on the applicability of global trial results to U.S. patients.
• If approved, this first-of-its-kind bispecific antibody combination could provide a much-needed, off-the-shelf, fixed-duration treatment option for transplant-ineligible patients who currently face poor prognosis.
Roche and Regeneron Announce Multi-Billion Dollar Investments in US Manufacturing Amid Tariff Concerns
• Roche has committed $50 billion to expand its US operations over five years, including new manufacturing facilities and R&D centers, with plans to create over 12,000 new jobs nationwide.
• Regeneron is investing more than $3 billion in US operations through a partnership with Fujifilm Diosynth Biotechnologies, nearly doubling its large-scale manufacturing capacity in the country.
• These pharmaceutical investments come as President Trump continues to threaten sector-specific tariffs, with Roche stating it will eventually export more medicines from the US than it imports.
Roche's OCREVUS Shows Strong Efficacy in MUSETTE Phase III Trial for Multiple Sclerosis
• Roche Holding's MUSETTE Phase III trial demonstrated strong efficacy of the approved 600 mg dose of OCREVUS for multiple sclerosis, reinforcing its position in the treatment landscape.
• The company has launched a new subcutaneous formulation of OCREVUS, expanding administration options for patients while continuing to build its neuromuscular disease portfolio.
• Roche has outperformed both the Swiss market and pharmaceutical industry with a 33.01% total shareholder return over the past year, bolstered by strategic collaborations and regulatory approvals.
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.
EMA Recommends Approval for New Cancer Treatments and Vaccines
• The European Medicines Agency (EMA) has recommended eight new products for EU-wide approval, expanding treatment options for various conditions.
• Several cancer treatments have received positive recommendations, potentially offering new hope for patients with different types of malignancies.
• A new antiparasitic combination has been endorsed for use in non-EU markets, addressing a critical need in regions affected by parasitic infections.
• The EMA is also reviewing new safety information regarding Leqembi, an Alzheimer's disease treatment, ensuring ongoing monitoring of its benefit-risk profile.
Novel Approaches Reshape Lymphoma Treatment Landscape: Bispecific Antibodies and MRD-Guided Therapy Show Promise
• Bispecific antibodies demonstrate remarkable response rates in both diffuse large B-cell and follicular lymphoma, with promising durability in frontline treatment settings.
• Groundbreaking ECOG-ACRIN trial reveals MRD-negative mantle cell lymphoma patients may not require stem cell transplantation, potentially changing decades of standard practice.
• Research initiatives are expanding to include older lymphoma patients and focus on quality-of-life outcomes, with new trial designs better reflecting real-world patient populations.
Avidity Biosciences Plans BLA Submission for Delpacibart Zotadirsen in DMD44 by Late 2025
• Avidity Biosciences plans to submit a Biologics License Application (BLA) for delpacibart zotadirsen (del-zota) to treat Duchenne muscular dystrophy amenable to exon 44 skipping (DMD44) by the end of 2025.
• The FDA has confirmed an accelerated approval pathway for del-zota, supported by clinical data from the EXPLORE44 program, potentially expediting its availability to patients.
• Avidity is on track to complete enrollment in the Phase 3 HARBOR trial for del-desiran in myotonic dystrophy type 1 (DM1) and initiate a pivotal trial for del-brax in facioscapulohumeral muscular dystrophy (FSHD) by mid-2025.
• To support these advancements, Avidity has expanded its leadership team, preparing for global commercialization and continued development of its Antibody Oligonucleotide Conjugates (AOCs) pipeline.
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.
Lisocabtagene Maraleucel Shows Promise in Relapsed/Refractory Lymphomas
• Lisocabtagene maraleucel (liso-cel) demonstrates efficacy and safety in second-line treatment of relapsed/refractory large B-cell lymphoma (LBCL), aligning with pivotal trial outcomes.
• The TRANSCEND FL trial indicates liso-cel achieved a significant overall response rate in relapsed/refractory marginal zone lymphoma (MZL), meeting the primary endpoint.
• Five-year data from TRANSCEND-NHL-001 underscore the curative potential of liso-cel in third-line LBCL, showing a 38% overall survival rate.
• Real-world data supports liso-cel's effectiveness across diverse LBCL patient subgroups, reinforcing its role as a standard-of-care treatment option.
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.
Zepbound Demonstrates Superior Weight Loss Over Wegovy; FDA Actions Advance Lung Cancer and Psoriatic Arthritis Therapies
• Eli Lilly's Zepbound showed a 47% greater relative weight loss compared to Novo Nordisk’s Wegovy in a head-to-head obesity study.
• Merck's sacituzumab tirumotecan (Sac-TMT) received FDA Breakthrough Therapy designation for advanced NSCLC with EGFR mutations.
• AstraZeneca's Imfinzi gained FDA approval for limited-stage small cell lung cancer (LS-SCLC) based on positive Phase III ADRIATIC trial data.
• J&J submitted applications to the FDA for Tremfya's use in pediatric patients with plaque psoriasis and juvenile psoriatic arthritis.
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.
Drug Development Updates
Stay informed with timely notifications on clinical trials, regulatory changes, and research advancements related to this medication.
© Copyright 2025. All Rights Reserved by MedPath