Genentech’s Phase III STARGLO Study Demonstrates Columvi Significantly Extends Survival in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma

– The study met its primary endpoint of overall survival with a 41% reduction in the risk of death in people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with Columvi plus chemotherapy –

– This Columvi combination could provide a much-needed off-the-shelf treatment option for people with transplant-ineligible R/R DLBCL –

– Data were featured in the congress Press Briefing and presented today in the Plenary Abstracts Session at EHA 2024 as a late-breaking oral presentation –

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today statistically significant and clinically meaningful results from its Phase III STARGLO study of Columvi^® (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) versus Rituxan^® (rituximab) in combination with GemOx (R-GemOx) for 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, or who have received two or more prior lines of therapy. Data were featured in the congress Press Briefing and presented today in the Plenary Abstracts Session at the European Hematology Association (EHA) 2024 Congress as a late-breaking oral presentation.

“The results from STARGLO are the first to show the potential of a CD20xCD3 bispecific antibody to make a difference in second or later-line DLBCL in people who are ineligible for transplant and have limited options,” said Jeremy Abramson, M.D., director, Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital Cancer Center, and principal investigator of the STARGLO study. “Glofitamab in combination with GemOx showed clinically significant improvement in overall survival, as well as key secondary endpoints, and the benefits were reinforced with an additional 11 months of follow-up.”

The primary analysis (median follow-up of 11.3 months) confirmed that the study met its primary endpoint of overall survival (OS), demonstrating that 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.

Pre-specified exploratory subgroup analyses showed comparable results, including consistency across the clinically relevant stratification factors of line of therapy (second-line versus third-line+) and outcome of last therapy (relapsed versus refractory). Regional inconsistencies were observed, however interpretation is limited given the exploratory nature of these analyses and small subgroups with wide confidence intervals.

“This marks a first step in advancing Columvi combinations in earlier settings to address the urgent need for the 40% of people who will relapse or have refractory disease and who have limited options,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Moreover, patients do not have to wait to start treatment with Columvi. This could be particularly important for patients with highly aggressive disease who are at risk of rapid disease progression.”

The Columvi combination also met its key secondary endpoints, with a 63% reduction in risk of disease worsening or death (progression-free survival, PFS) compared to R-GemOx (HR=0.37; 95% CI: 0.25–0.55, p<0.0001). A follow-up analysis was conducted after all patients had completed therapy (median follow-up of 20.7 months), which showed continued benefit in both primary and secondary endpoints. Median OS for people treated with the Columvi combination was 25.5 months, nearly double what was seen for people treated with R-GemOx at 12.9 months, and more than twice as many patients experienced a complete response (58.5% versus 25.3%, respectively).

Adverse event (AE) rates were higher with the Columvi combination versus R-GemOx, noting higher median number of cycles received with 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.

Columvi is the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomized Phase III trial, demonstrating the potential of this type of therapeutic combination to improve survival outcomes in earlier lines of treatment. The standard second-line therapy for R/R DLBCL patients has historically been high-dose chemotherapy followed by stem-cell transplant, however, not everyone with R/R DLBCL is a candidate due to age or coexisting medical conditions. Newer therapies are also becoming available, but barriers remain for many, and alternative treatment options are needed for these patients. Columvi is given as a fixed-duration treatment, offering people with R/R DLBCL a treatment end date and the possibility of a treatment-free period, unlike continuous treatments.

Results from the STARGLO study will be submitted to global health authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency.

Columvi is also being investigated in other aggressive, hard-to-treat lymphomas and was recently granted Breakthrough Therapy Designation by the FDA for the treatment of adult patients with relapsed or refractory mantle cell lymphoma who have received at least two prior therapies based on results from the Phase I/II NP30179 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 are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability.

STARGLO is intended as a confirmatory study to convert Columvi’s accelerated approval 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.

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.

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. A clinical development program for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma and other blood cancers.

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 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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