Glofitamab

COLUMVI is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). COLUMVI is a bispecific CD20-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.

Glofitamab-gxbm is a bispecific antibody that binds to CD20 expressed on the surface of B cells, and to CD3 receptor expressed on the surface of T cells. Glofitamab-gxbm causes T-cell activation and proliferation, secretion of cytokines, and the lysis of CD20-expressing B cells. Glofitamab-gxbm showed anti-tumor activity in vivo in mouse models of DLBCL.

Pretreat with a single 1,000 mg dose of obinutuzumab intravenously 7 days before initiation of COLUMVI (Cycle 1 Day 1). Administer premedications as recommended. Administer only as an intravenous infusion. Recommended dosage: Treatment Cycle Cycle = 21 days Day Dose of COLUMVI Day 1 Obinutuzumab 1,000 mg Cycle 1 Day 8 Step-up dose 1 2.5 mg Day 15 Step-up dose 2 10 mg Cycle 2 to 12 Day 1 30 mg Administer in a facility equipped to monitor and manage CRS. Patients should be hospitalized for the 2.5 mg step-up dose and for subsequent infusions as recommended. See Full Prescribing Information for instructions on preparation and administration.

None. None.

Boxed warning (cytokine release syndrome): Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving COLUMVI. Premedicate before each dose, and initiate treatment with the COLUMVI step-up dosing schedule to reduce the risk of CRS. Withhold COLUMVI until CRS resolves or permanently discontinue based on severity. Neurologic Toxicity: Can cause serious neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Monitor for neurologic toxicity, withhold or permanently discontinue based on severity. Serious Infections: Can cause serious or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Tumor Flare: Can cause serious tumor flare reactions. Monitor patients at risk for complications of tumor flare. Embryo-Fetal Toxicity: May cause fetal harm.

The following clinically significant adverse reactions are described elsewhere in the labeling: Cytokine Release Syndrome Neurologic Toxicity Serious Infections Tumor Flare The most common (≥ 20%) adverse reactions, excluding laboratory abnormalities, are cytokine release syndrome, musculoskeletal pain, rash, and fatigue. The most common (≥ 20%) Grade 3 to 4 laboratory abnormalities are lymphocyte count decreased, phosphate decreased, neutrophil count decreased, uric acid increased, and fibrinogen decreased.

For certain CYP substrates where minimal concentration changes may lead to serious adverse reactions, monitor for toxicities or drug concentrations of such CYP substrates when coadministered with COLUMVI. Glofitamab-gxbm causes the release of cytokines that may suppress the activity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur after the first dose of COLUMVI on Cycle 1 Day 8 and up to 14 days after the first 30 mg dose on Cycle 2 Day 1 and during and after CRS.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.