FDA Accepts Supplemental Biologics License Application for Genentech’s Columvi Combination for People With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Rhea-AI Summary

Genentech announced FDA acceptance of a supplemental Biologics License Application (sBLA) for Columvi in combination with gemcitabine and oxaliplatin (GemOx) for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The application is based on the Phase III STARGLO study, which demonstrated statistically significant improvement in overall survival compared to Rituxan with GemOx.

The FDA decision is expected by July 20, 2025. This treatment could provide an off-the-shelf, fixed-duration option for patients who aren't eligible for stem cell transplant. Columvi is currently approved in over 50 countries as a monotherapy for R/R DLBCL after two or more lines of systemic therapy.

Positive

• Phase III STARGLO study showed statistically significant improvement in overall survival
• First CD20xCD3 bispecific antibody to demonstrate survival benefit in DLBCL in a Phase III trial
• Already approved in 50+ countries for R/R DLBCL
• Safety profile consistent with known individual medicines

Negative

• None.

– Application is based on data from the Phase III STARGLO study where Columvi plus chemotherapy showed a statistically significant and clinically meaningful improvement in overall survival –

– This regimen could provide an off-the-shelf, fixed-duration treatment option for patients to start soon after diagnosis, which is important for those who are at high-risk of disease progression –

– Improving survival outcomes is needed for people with an aggressive disease like relapsed or refractory DLBCL, especially those who aren’t eligible for transplant –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) for Columvi^® (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant. The FDA is expected to make a decision on approval by July 20, 2025.

The standard second-line therapy for R/R DLBCL patients has historically been high-dose chemotherapy followed by stem-cell transplant, however, not all patients are a candidate due to age or coexisting medical conditions. While newer therapies are becoming available, barriers remain for many and alternative treatment options are needed for these patients to improve survival outcomes.

“For people with aggressive lymphomas like DLBCL, timely intervention with effective therapies can be crucial to reduce the risk of disease progression and improve long-term outcomes,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “We are encouraged by the overall survival benefit seen with this Columvi combination and hope it can become an important treatment option for those who are in need of alternative therapies.”

The sBLA is based on results from the Phase III STARGLO study, which were presented at the European Hematology Association Congress earlier this year and recently published in The Lancet. Data showed Columvi in combination with GemOx demonstrated a statistically significant and clinically meaningful overall survival (OS) improvement versus Rituxan^® (rituximab) and GemOx (R-GemOx), making it the first CD20xCD3 bispecific antibody to show a survival benefit in DLBCL in a randomized Phase III trial. Safety of the combination appeared consistent with the known safety profiles of the individual medicines.

Data from the STARGLO study have been submitted to other health authorities around the world for approval consideration, including the European Medicines Agency.

Columvi is part of Genentech’s industry-leading CD20xCD3 bispecific antibody program, which has seen more than 3,000 patients treated in clinical trials and more than 2,600 treated in clinical practice to date. Columvi was the first fixed-duration bispecific antibody to receive accelerated approval by the U.S. FDA and conditional marketing authorization in the EU as a monotherapy to treat people with R/R DLBCL after two or more lines of systemic therapy and is currently approved in more than 50 countries around the world.

As part of Genentech’s efforts to elevate treatment standards in the earlier stages of DLBCL, where there is the best opportunity to improve long-term outcomes and prevent relapse, Columvi is also being investigated in combination with Polivy^® (polatuzumab vedotin-piiq), Rituxan, cyclophosphamide, doxorubicin and prednisone (R-CHP) in previously untreated DLBCL in the Phase III SKYGLO study.

About the STARGLO Study

The STARGLO study [GO41944; NCT04408638] is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Columvi^® (glofitamab-gxbm) in combination with gemcitabine plus oxaliplatin (GemOx) versus Rituxan^® (rituximab) in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and who are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Preclinical research indicated an increased antitumor effect when combining Columvi with GemOx over GemOx alone, so the STARGLO study was initiated to further explore the potential complementary effects of the treatment combination. Outcome measures include overall survival (OS; primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability.

In the primary analysis (conducted after a median follow-up of 11.3 months) patients treated with Columvi plus GemOx lived significantly longer, with a 41% reduction in the risk of death (hazard ratio [HR]=0.59, 95% CI: 0.40-0.89, p=0.011) versus R-GemOx. Median OS was not reached with the Columvi regimen versus nine months for R-GemOx. Safety of the combination appeared consistent with the known safety profiles of the individual medicines. Adverse event (AE) rates were higher with the Columvi combination versus R-GemOx, noting higher median number of cycles received with the Columvi combination (11 versus 4). One of the most common AEs was cytokine release syndrome, which was generally low grade (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and occurred primarily in Cycle 1.

STARGLO is intended as a confirmatory study to convert the accelerated approval of Columvi in the U.S. and conditional marketing authorization in the EU to full approvals for people with R/R DLBCL after two or more lines of systemic therapy based on the pivotal Phase I/II NP30179 study [NCT03075696].

About Columvi^® (glofitamab-gxbm)

Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Columvi is part of Genentech’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development program that also includes Lunsumio^® (mosunetuzumab), which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Genentech is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma and mantle cell lymphoma.

About Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma (NHL) in the U.S. While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes. DLBCL not otherwise specified is the most common category of large B-cell lymphoma (LBCL) and accounts for about 80% or more of cases. It applies to cases that do not fall into any specific disease subgroups of LBCL.

Columvi U.S. Indication

Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer.

It is not known if Columvi is safe and effective in children.

The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about Columvi?

Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death.

Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including:

• fever of 100.4°F (38°C) or higher
• chills or shaking
• fast or irregular heartbeat
• dizziness or light-headedness
• trouble breathing
• shortness of breath

Due to the risk of CRS, you will receive Columvi on a “step-up dosing schedule”.

• A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1).
• You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller “step-up” doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose.
• You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2).
• If your dose of Columvi is delayed for any reason, you may need to repeat the “step-up dosing schedule”.
• If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi.
• Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions.

Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects.

Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away.

What are the possible side effects of Columvi?

Columvi may cause serious side effects, including:

• Cytokine Release Syndrome.
• Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:
  • headache
  • confusion and disorientation
  • difficulty paying attention or understanding things
  • trouble speaking
  • sleepiness
  • memory problems
  • numbness, tingling, or weakness of the hands or feet
  • dizziness
  • shaking (tremors)

• Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat.
• Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare:
  • tender or swollen lymph nodes
  • pain or swelling at the site of the tumor
  • chest pain
  • cough
  • trouble breathing

The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness.

The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).

Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects.

Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection
• have kidney problems
• are pregnant or plan to become pregnant. Columvi may harm your unborn baby
• Females who are able to become pregnant:
  • Your healthcare provider should do a pregnancy test before you start treatment with Columvi.
  • You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time.
  • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi.
• are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving Columvi?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.

These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi.

You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit https://www.Columvi.com.

About Polivy^® (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines (a rituximab product, cyclophosphamide, doxorubicin, and prednisone) as a first treatment for adults who have moderate to high risk diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL).

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat DLBCL in adults who have progressed after at least 2 prior therapies.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. Your doctor may stop or adjust your treatment if any serious side effects occur. Be sure to contact your healthcare team if there are any signs of these side effects.

• Nerve problems in your arms and legs: This may happen as early as after your first dose and may worsen with every dose. Your doctor will monitor for signs and symptoms, such as changes in your sense of touch, numbness or tingling in your hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to your walking pattern
• Infusion-related reactions: You may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of your infusion
• Low blood cell counts: Treatment with Polivy can cause severe low blood cell counts. Your doctor will monitor your blood counts throughout treatment with Polivy
• Infections: If you have a fever of 100.4°F (38°C) or higher, chills, cough, or pain during urination, contact your healthcare team. Your doctor may also give you medication before giving you Polivy, which may prevent some infections
• Rare and serious brain infections: Your doctor will monitor closely for signs and symptoms of these types of infections. Contact your doctor if you experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
• Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
• Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of your skin or the white part of your eyes. You may be at higher risk if you already had liver problems or you are taking other medication

Side effects seen most often

The most common side effects during treatment were

• Nerve problems in arms and legs
• Nausea
• Tiredness or lack of energy
• Diarrhea
• Constipation
• Hair loss
• Redness and sores of the lining of the mouth, lips, throat, and digestive tract

Polivy may lower your red or white blood cell counts and increase uric acid levels.

Polivy may not be for everyone. Talk to your doctor if you are

• Pregnant or think you are pregnant: Data have shown that Polivy may harm your unborn baby
• Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for 5 months after their last Polivy treatment
• Breastfeeding: Women should not breastfeed while taking Polivy and for 2 months after the last dose

These may not be all the side effects. Talk to your healthcare provider for more information about the benefits and risks of Polivy treatment.

You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see the full Prescribing Information and visit https://www.Polivy.com for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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Source: Genentech

FAQ

When is the FDA expected to decide on Columvi's sBLA approval for RHHBY?

The FDA is expected to make a decision on approval by July 20, 2025.

What were the key results of the STARGLO Phase III trial for Columvi?

The STARGLO trial showed Columvi with GemOx achieved statistically significant and clinically meaningful overall survival improvement versus Rituxan and GemOx in DLBCL patients.

How many countries have approved Columvi (RHHBY) for R/R DLBCL treatment?

Columvi is currently approved in more than 50 countries as a monotherapy for R/R DLBCL after two or more lines of systemic therapy.

What patient population will Columvi target with this new sBLA for RHHBY?

The treatment targets people with relapsed or refractory DLBCL who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant.