Glofitamab

Glofitamab is an IV infusion used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL). Its brand name is Columvi and it is manufactured by Genentech Inc.

Glofitamab is FDA-approved for adults with:

• diffuse large B-cell lymphoma, that has returned or not responded to treatment (relapsed or refractory), not otherwise specified (DLBCL, NOS)
• large B-cell lymphoma (LBCL) arising from follicular lymphoma, when 2 or more treatment courses have already been given.

It is not known if this medicine is safe and effective in children.

Glofitamab gained FDA approval on June 15, 2023, under the brand name Columvi. Its approval is under the accelerated approval designation, which means continued approval may be dependent upon a further benefit being shown in clinical trials.

Glofitamab has a bispecific mechanism of action and binds to 2 different immune system targets: the CD20 protein on B cells and the CD3 protein on T cells. This brings T cells into proximity to B cells, making them more effective at killing cancerous B cells.

Glofitamab belongs to the drug class called Bispecific T-cell engagers (BiTE).

Research shows that treatment with glofitamab (Columvi) effectively treats B-cell lymphomas, with clinical trials showing:

• An overall response rate of 56%
• 43% of patients experienced a complete response to therapy
• 68.5% of patients maintained their response for 9 months or longer
• Median duration of response was 18.4 months.

Glofitamab carries a Boxed Warning for cytokine release syndrome.

Cytokine Release Syndrome (CRS)

Glofitamab can cause CRS, a serious side effect that is common during treatment and can also be serious and lead to death. Tell your healthcare provider or get medical help right away if you develop any signs orsymptoms 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 glofitamab on a "step-up dosing schedule".

• The "step-up dosing schedule" is when you receive smaller "step-up" doses of glofitamab to help reduce your risk of CRS.
• You will receive a medicine called obinutuzumab on the first day of your first treatment cycle (Day 1 of Cycle 1). You will start the glofitamab "step-up dosing schedule" a week after the obinutuzumab dose.
• You will receive smaller "step-up" doses of glofitamab on Day 8 and Day 15 of Cycle 1.
• You will receive your first full dose of glofitamab a week after the second "step-up" dose (this will be Day 1 of Cycle 2).
• Before each dose of glofitamab, you will receive medicines to help reduce your risk of CRS and infusion-related reactions.
• You should be hospitalized during your infusion and for 24 hours: after receiving the first "step-up" dose on Day 8 of Cycle 1. after receiving the second "step-up dose" on Day 15 of Cycle 1, if you experienced CRS during the first "step-up" dose. if you had more than mild CRS with your previous dose of glofitamab.
• If your dose of Glofitamab is delayed for any reason, you may need to repeat the "step-up dosing schedule".
• Your healthcare provider will monitor you for CRS during treatment with glofitamab and may treat you in a hospital if you develop signs and symptoms of CRS.
• See "How will I receive glofitamab?" for more information about how you will receive glofitamab.
• Your healthcare provider may temporarily stop or completely stop your treatment with glofitamab 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 glofitamab Patient Wallet Card lists the signs and symptoms of CRS that you should get medical help for right away.

See below for more information about side effects.

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

• have an infection
• are pregnant or plan to become pregnant. Glofitamab may harm your unborn baby. Females who can become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with glofitamab. Use effective birth control (contraception) during treatment and for 1 month after your last dose of glofitamab. 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 glofitamab.
• are breastfeeding or plan to breastfeed. It is not known if glofitamab passes into your breastmilk. Do not breastfeed during treatment and for 1 month after your last dose of glofitamab.

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

Common side effects

The most common side effects of glofitamab are: cytokine release syndrome (CRS), muscle and bone pain, rash, and tiredness.

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

Serious side effects

See Important information above. Glofitamab can cause other serious side effects, such as:

• Neurologic problems. Glofitamab can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with glofitamab. 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. Glofitamab can cause serious infections that may lead to death, including progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal viral disease that damages the brain's white matter. 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 infection, including fever, chills, weakness, loss of balance or trouble walking, vision changes, cough, shortness of breath, sore throat, difficulty speaking, or confusion.
• 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.

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

These are not all the possible side effects of glofitamab. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Glofitamab will be given to you by your healthcare provider by infusion through a needle placed in your vein (intravenous infusion).

Your glofitamab treatment schedule is divided into cycles that are 21 days (3 weeks) long.

• On Day 1 of Cycle 1, your healthcare provider will give you a medicine called obinutuzumab by intravenous infusion.
• On Day 8 and Day 15 of Cycle 1, you will receive “step-up” doses of Glofitamab.
• Starting with Cycle 2, you will receive a full dose of glofitamab 1 time every three weeks.

Your healthcare provider will decide how many treatment cycles you will receive of glofitamab.

See also Important information above.

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.

See Side effects above for more information about signs and symptoms of neurological problems.

Active ingredient: glofitamab-gxbmInactive ingredients (Columvi): histidine, histidine hydrochloride monohydrate, methionine, polysorbate 20, sucrose, and Water for injection.

Available in two strengths:

• Glofitamab 2.5 mg/2.5 mL (1 mg/mL) in a single-dose vial
• Glofitamab 10 mg/10 mL (1 mg/mL) in a single-dose vial.

The injection is preservative-free and should be colorless and clear.

Glofitamab injection is manufactured by Genentech Inc., a member of the Roche group, 1 DNA Way, South San Francisco, CA 94080-4990. U.S. License No.: 1048.