COLUMVI

Glofitamab-gxbm is a bispecific CD20-directed CD3 T-cell engager. It is a recombinant humanized anti-CD20 anti-CD3ɛ bispecific immunoglobulin G1 (IgG1) monoclonal antibody produced in Chinese hamster ovary (CHO) cells. Glofitamab-gxbm has an approximate molecular weight of 197 kDa. COLUMVI (glofitamab-gxbm) injection is a sterile, preservative-free, colorless, clear solution supplied in single-dose vials for intravenous infusion. COLUMVI is supplied in 2.5 mg/2.5 mL and 10 mg/10 mL single-dose vials at a concentration of 1 mg/mL. Each mL of solution contains 1 mg glofitamab-gxbm, histidine (0.63 mg), histidine hydrochloride monohydrate (3.34 mg), methionine (1.49 mg), polysorbate 20 (0.5 mg), sucrose (82.15 mg), and Water for Injection, USP, at pH 5.5.

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 [see Clinical Studies (14.1) ] . 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. 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). ( 1 )

Pretreat with a single 1,000 mg dose of obinutuzumab intravenously 7 days before initiation of COLUMVI (Cycle 1 Day 1). ( 2.2 ) Administer premedications as recommended. ( 2.3 ) Administer only as an intravenous infusion. ( 2.1 ) Recommended dosage ( 2.2 ): 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. ( 2.1 , 2.2 ) Patients should be hospitalized for the 2.5 mg step-up dose and for subsequent infusions as recommended. ( 2.1 , 2.2 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.5 , 2.6 , 2.7 ) 2.1 Important Dosing Information Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2-micron in-line filter. Administer COLUMVI diluted solution via intravenous bag infusion. The 2.5 mg dose may alternatively be administered via intravenous syringe infusion [see Dosage and Administration (2.5 , 2.6 , 2.7 )] . COLUMVI should only be administered by a healthcare professional with immediate access to appropriate medical support, including supportive medications to manage severe CRS [see Dosage and Administration (2.4) ] . Ensure adequate hydration before administering COLUMVI. Premedicate before each dose [see Dosage and Administration (2.3) ] . Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing schedule in Table 1 with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS [see Dosage and Administration (2.3) ] . Due to the risk of CRS, patients should be hospitalized during and for 24 hours after completion of infusion of step-up dose 1 (2.5 mg on Cycle 1 Day 8) [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1 [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next COLUMVI infusion. 2.2 Recommended Dosage Pretreatment with Obinutuzumab Pretreat all patients with a single 1,000 mg dose of obinutuzumab administered as an intravenous infusion on Cycle 1 Day 1, 7 days prior to initiation of COLUMVI (see Table 1 ) to deplete the circulating and lymphoid tissue B cells. Obinutuzumab should be administered as an intravenous infusion at 50 mg/hour. The rate of infusion can be escalated in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. Refer to the obinutuzumab prescribing information for complete dosing information. COLUMVI Step-up Dose Schedule COLUMVI dosing begins with a step-up dose schedule. Following completion of pretreatment with obinutuzumab on Cycle 1 Day 1, administer COLUMVI as an intravenous infusion according to the step-up dose schedule in Table 1 . Administer premedications for each dose of COLUMVI as described in Table 3 [see Dosage and Administration (2.3) ]. Table 1: COLUMVI Dosing Schedule (21-Day Treatment Cycles) Treatment cycle Day Dose of COLUMVI Duration of infusion Cycle 1 Day 1 Obinutuzumab Refer to " Pretreatment with obinutuzumab " described above. Day 8 Step-up dose 1 2.5 mg 4 hours For patients who experience CRS with their previous dose of COLUMVI, the time of infusion may be extended up to 8 hours. Day 15 Step-up dose 2 10 mg Cycle 2 Day 1 30 mg 4 hours Cycle 3 to 12 Day 1 30 mg 2 hours If the patient experienced CRS with the previous dose, the duration of infusion should be maintained at 4 hours. Continue COLUMVI for a maximum of 12 cycles (inclusive of Cycle 1 step-up dosing) or until disease progression or unacceptable toxicity, whichever occurs first. Monitoring for Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Administer the COLUMVI infusions intravenously in a healthcare setting with immediate access to medical support to manage CRS, including severe CRS. For the first COLUMVI step-up dose (2.5 mg on Cycle 1 Day 8), patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion. Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1. For subsequent infusions (30 mg on Day 1 of Cycle 2 or subsequent cycles), patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after completion of the next COLUMVI infusion. For monitoring after delayed or missed doses of COLUMVI, follow the recommendations in Table 2 . Delayed or Missed Doses If a dose of COLUMVI is delayed, restart therapy based on the recommendations made in Table 2 , then resume the treatment schedule accordingly. For repeat of the 2.5 mg dose patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion. For the repeat of the 10 mg dose, patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion if any grade CRS occurred during the most recent 2.5 mg dose. Table 2: Recommendations for Restarting COLUMVI After Dose Delay Last Dose Administered Time Since Last Dose Administered Action for Next Dose(s) Administer premedication as per Table 3 for all patients. Obinutuzumab pretreatment (Cycle 1 Day 1) ≤ 2 weeks Administer COLUMVI 2.5 mg (Cycle 1 Day 8) Patients should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg dose. , then resume the planned treatment schedule. > 2 weeks Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1). Then administer COLUMVI 2.5 mg (Cycle 1 Day 8) and resume the planned treatment schedule. COLUMVI 2.5 mg (Cycle 1 Day 8) ≤ 2 weeks Administer COLUMVI 10 mg (Cycle 1 Day 15) Patients should be hospitalized during and for 24 hours after completing infusion of the 10 mg dose if CRS occurred during the most recent 2.5 mg dose. , then resume the planned treatment schedule. > 2 to ≤ 4 weeks Repeat COLUMVI 2.5 mg (Cycle 1 Day 8) . Then administer COLUMVI 10 mg (Cycle 1 Day 15) and resume the planned treatment schedule. > 4 weeks Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1) and COLUMVI 2.5 mg (Cycle 1 Day 8) . Then administer COLUMVI 10 mg (Cycle 1 Day 15) and resume the planned treatment schedule. COLUMVI 10 mg (Cycle 1 Day 15) ≤ 2 weeks Administer COLUMVI 30 mg (Cycle 2 Day 1), then resume the planned treatment schedule. > 2 to ≤ 6 weeks Repeat COLUMVI 10 mg (Cycle 1 Day 15). Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule. > 6 weeks Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1), COLUMVI 2.5 mg (Cycle 1 Day 8) , and COLUMVI 10 mg (Cycle 1 Day 15) . Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule. COLUMVI 30 mg (Cycle 2 onwards) ≤ 6 weeks Administer COLUMVI 30 mg, then resume the planned treatment schedule. > 6 weeks Repeat the Cycle 1 regimen described in Table 1 : obinutuzumab 1,000 mg pretreatment (Day 1), COLUMVI 2.5 mg (Day 8) , and COLUMVI 10 mg (Day 15) . Then administer COLUMVI 30 mg (Day 1 of next cycle) and resume the planned treatment schedule. 2.3 Recommended Premedication and Prophylactic Medications Premedication Administer the following premedications to reduce the risk of CRS and infusion-related reactions [see Warnings and Precautions (5.1) ] . Table 3: Premedications to be Administered for COLUMVI Infusion Day of Treatment Cycle Patients requiring premedication Premedication Administration Cycle 1, Day 8 and Day 15; Cycle 2; Cycle 3 Dexamethasone 20 mg intravenously If dexamethasone is not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg intravenously. Completed at least 1 hour prior to COLUMVI infusion. All patients Acetaminophen 500 mg to 1,000 mg orally At least 30 minutes before COLUMVI infusion. Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent) Completed at least 30 minutes before COLUMVI infusion. All subsequent infusions All patients Acetaminophen 500 mg to 1,000 mg orally At least 30 minutes before COLUMVI infusion. Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent) Completed at least 30 minutes before COLUMVI infusion. Patients who experienced any grade CRS with the previous dose Dexamethasone 20 mg intravenously Completed at least 1 hour prior to COLUMVI infusion. Tumor Lysis Syndrome Prophylaxis Before starting COLUMVI, administer anti-hyperuricemics to patients at risk of tumor lysis syndrome, ensure adequate hydration status, and monitor as appropriate [see Adverse Reactions (6.1) ] . Infection Prophylaxis Before starting COLUMVI, consider initiation of antiviral prophylaxis to prevent herpes virus reactivation. Consider prophylaxis for cytomegalovirus infection, pneumocystis jirovecii pneumonia (PJP), and other opportunistic infections in patients at increased risk [see Warnings and Precautions (5.3) ] . 2.4 Dosage Modifications for Adverse Reactions No dosage reduction for COLUMVI is recommended. Cytokine Release Syndrome Identify CRS based on clinical presentation [see Warnings and Precautions (5.1) ] . Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, withhold COLUMVI and manage according to the recommendations in Table 4 and current practice guidelines. Administer supportive care for CRS, which may include intensive care for severe or life-threatening cases. Table 4: Recommendations for Management of Cytokine Release Syndrome Grade American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria. Presenting Symptoms Actions Grade 1 Temperature ≥ 100.4°F (38°C) Premedication may mask fever. Therefore, if clinical presentation is consistent with CRS, follow these management guidelines. Withhold COLUMVI and manage per current practice guidelines. If symptoms resolve, restart infusion at a slower rate. Duration of infusion may be extended up to 8 hours, as appropriate for that cycle (see Table 1 ). Ensure CRS symptoms are resolved for at least 72 hours before next dose. Refer to Table 2 for information on restarting COLUMVI after dose delays [see Dosage and Administration (2.2) ] . Consider slower infusion rate for next dose. Grade 2 Temperature ≥ 100.4°F (38°C) with: Hypotension not requiring vasopressors and/or Hypoxia requiring low-flow oxygen Low-flow oxygen defined as oxygen delivered at < 6 L/minute, high-flow oxygen defined as oxygen delivered at ≥ 6 L/minute. by nasal cannula or blow-by Withhold COLUMVI and manage per current practice guidelines. If symptoms resolve, restart infusion at a slower rate. Ensure CRS symptoms are resolved for at least 72 hours before next dose. For the next dose, consider a slower infusion rate, monitor more frequently, and consider hospitalization. For recurrent Grade 2 CRS, manage per Grade 3 CRS. Grade 3 Temperature ≥ 100.4°F (38°C) with: Hypotension requiring vasopressor (with or without vasopressin) and/or Hypoxia requiring high-flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi mask Withhold COLUMVI and manage per current practice guidelines, which may include intensive care. Ensure CRS symptoms are resolved for at least 72 hours before next dose. Hospitalize for the next dose, monitor more frequently, and consider a slower infusion rate. For recurrent Grade 3 CRS, permanently discontinue COLUMVI. Grade 4 Temperature ≥ 100.4°F (38°C) with: Hypotension requiring multiple vasopressors (excluding vasopressin) and/or Hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation) Permanently discontinue COLUMVI and manage per current practice guidelines, which may include intensive care. Neurologic Toxicity, Including ICANS Management recommendations for neurologic toxicity, including ICANS, is summarized in Table 5 . At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding COLUMVI based on the type and severity of neurotoxicity. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care. Table 5: Recommended Dosage Modification for Neurologic Toxicity (Including ICANS) Adverse Reaction Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. , Based on ASTCT 2019 grading for ICANS. Actions Grade 1 Continue COLUMVI and monitor neurologic toxicity symptoms. If ICANS, manage per current practice guidelines. Grade 2 Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline. Consider the type of neurologic toxicity before deciding to withhold COLUMVI. , See Dosage and Administration (2.2) on restarting COLUMVI after dose delays. Provide supportive therapy, and consider neurologic evaluation. If ICANS, manage per current practice guidelines. Neurologic Toxicity (including ICANS ) [see Warnings and Precautions (5.2) ] Grade 3 Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 7 days. , Evaluate benefit-risk before restarting COLUMVI. For Grade 3 neurologic events lasting more than 7 days, consider permanently discontinuing COLUMVI. Provide supportive therapy, and consider neurology evaluation. If ICANS, manage per current practice guidelines. Grade 4 Permanently discontinue COLUMVI. Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines. Other Adverse Reactions Table 6: Recommended Dosage Modifications for Other Adverse Reactions Adverse Reactions Based on NCI CTCAE, version 4.03. Severity Actions Infections [see Warnings and Precautions (5.3) ] Grades 1 – 4 Withhold COLUMVI in patients with active infection until the infection resolves. See Dosage and Administration (2.2) on restarting COLUMVI after dose delays. For Grade 4, consider permanent discontinuation of COLUMVI. Grade 1 Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare. Tumor flare [see Warnings and Precautions (5.4) ] Grades 2 – 4 Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment including antihistamine and corticosteroids. Withhold COLUMVI until tumor flare resolves. Neutropenia Absolute neutrophil count less than 0.5 × 10 9 /L Withhold COLUMVI until absolute neutrophil count is 0.5 × 10 9 /L or higher. Thrombocytopenia Platelet count less than 50 × 10 9 /L Withhold COLUMVI until platelet count is 50 × 10 9 /L or higher. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 or higher Withhold COLUMVI until the toxicity resolves to Grade 1 or baseline. 2.5 Preparation into an Intravenous Bag This section describes preparation of all doses of COLUMVI into an intravenous bag. For preparation instructions for the 2.5 mg dose into an intravenous syringe, see subsection 2.6 [see Dosage and Administration (2.6) ] . Preparation Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles. Use aseptic technique when preparing the COLUMVI diluted solution for intravenous infusion. Dilution for Intravenous Bag Infusion Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed (see Table 7 ). Select an appropriate size infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection (see Table 7 ). COLUMVI diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or polyolefin. COLUMVI diluted with 0.45% Sodium Chloride Injection is compatible with intravenous infusion bags composed of PVC. Prepare the infusion bag by withdrawing and discarding the volume from the infusion bag according to Table 7 . Withdraw the required volume of COLUMVI from the vial(s) using a sterile needle and syringe and dilute into the infusion bag to a final concentration of 0.1 mg/mL to 0.6 mg/mL according to Table 7 . Table 7: Dilution of COLUMVI into an intravenous infusion bag Dose of COLUMVI Size of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection infusion bag Volume to be withdrawn and discarded from the infusion bag Volume of COLUMVI to be added to the infusion bag Total volume to be infused 2.5 mg 50 mL 27.5 mL 2.5 mL 25 mL 10 mg 50 mL 10 mL 10 mL 50 mL 100 mL 10 mL 10 mL 100 mL 30 mg 50 mL 30 mL 30 mL 50 mL 100 mL 30 mL 30 mL 100 mL Discard any unused COLUMVI left in the vial. Gently invert the infusion bag to mix the solution, in order to avoid excess foaming. Do not shake. 2.6 Preparation of 2.5 mg Dose into an Intravenous Syringe This section describes the alternative method of preparation of the 2.5 mg dose of COLUMVI into an intravenous syringe. For preparation instructions for all doses into an intravenous infusion bag, see subsection 2.5 [see Dosage and Administration (2.5) ] . Preparation Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles. Use aseptic technique when preparing the COLUMVI diluted solution for intravenous syringe infusion. Dilution for Intravenous Syringe Infusion (Alternative Method for 2.5 mg Dose Only) Draw 22.5 mL of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection into a 30 mL syringe composed of PP (see Table 8 ). Withdraw 2.5 mL of COLUMVI from the vial using a sterile needle into a second syringe (see Table 8 ). Discard any unused COLUMVI left in the vial. Attach a connector to the two syringes and transfer COLUMVI into the 30 mL syringe. The final concentration of COLUMVI should be 0.1 mg/mL. Table 8: Dilution of COLUMVI into an intravenous syringe Dose of COLUMVI Volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to be added to the syringe Volume of COLUMVI to be added to the syringe Total volume to be infused 2.5 mg 22.5 mL 2.5 mL 25 mL Disconnect the syringes. Draw air into the syringe containing the COLUMVI diluted solution and close. Gently invert the syringe to mix the solution, in order to avoid excessive foaming. Do not shake. Remove air bubbles from the syringe before administration. 2.7 Storage and Administration Storage of Diluted Product Immediately use diluted COLUMVI solution. If not used immediately, the diluted solution can be stored: Refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours, or At room temperature up to 25°C (77°F) for up to 4 hours. Do not freeze the diluted infusion solution. Discard diluted infusion solution if storage time exceeds these limits. COLUMVI Administration Administer COLUMVI as an intravenous infusion only through a dedicated infusion line that includes a sterile 0.2-micron in-line filter using an intravenous infusion pump or syringe pump. Prime the infusion line with the diluted infusion solution. No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), PVC, PE, polybutadiene (PBD), polyetherurethane (PEU), polycarbonate (PC), silicone, polytetrafluoroethylene (PTFE), or acrylonitrile butadiene styrene (ABS), and in-line filter membranes composed of polyethersulfone (PES) or polysulfone. See Table 1 for duration of infusion. The maximum time for the administration of the diluted infusion solution may be extended up to 8 hours (see Table 4 ). To ensure the entire dose of COLUMVI is administered, replace the empty infusion bag or syringe with an infusion bag or syringe containing 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection connected to the same infusion line. Continue the infusion at the same rate until the recommended infusion duration is reached according to Table 1 . Do not mix COLUMVI with other drugs.

None. None. ( 4 )

The following clinically significant adverse reactions are described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity [see Warnings and Precautions (5.2) ] Serious Infections [see Warnings and Precautions (5.3) ] Tumor Flare [see Warnings and Precautions (5.4) ] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma Study NP30179 The safety of COLUMVI was evaluated in Study NP30179, a multi-cohort, multicenter, single-arm clinical trial that included 154 adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy [see Clinical Studies (14.1) ] . The trial required an ECOG performance status of 0 or 1, absolute neutrophil count ≥ 1,500/µL, platelet count ≥ 75,000/µL independent of transfusion, serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CLcr) ≥ 50 mL/min, and hepatic transaminases ≤ 3 × ULN. The trial excluded patients with active or previous central nervous system (CNS) lymphoma or CNS disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic hematopoietic stem cell transplantation (HSCT). Patients received pretreatment with a single dose of obinutuzumab on Day 1 of Cycle 1 (seven days prior to start of COLUMVI). Following premedication, COLUMVI was administered by intravenous infusion according to the step-up dosing schedule with 2.5 mg on Day 8 of Cycle 1, and 10 mg on Day 15 of Cycle 1. Patients received the 30 mg COLUMVI dose by intravenous infusion on Day 1 of subsequent cycles for a maximum of 12 cycles (including step-up dosing). Each cycle was 21 days. Patients were hospitalized during and for 24 hours following completion of at least the first step-up dose. Of the 154 patients who initiated study treatment, 145 received COLUMVI; nine patients (6%) did not receive COLUMVI due to infection, progressive disease, or patient decision. Patients received a median of 5 cycles of COLUMVI with 30% receiving all 12 cycles of COLUMVI. Of patients who received COLUMVI, the median age was 66 years (range: 21 to 90 years); 66% were male; 77% were White, 4.8% were Asian, 1.4% were Black or African American, 6% were Hispanic or Latino. The main diagnoses were DLBCL, NOS and LBCL arising from follicular lymphoma. Serious adverse reactions occurred in 48% of patients who received COLUMVI. Serious adverse reactions in ≥ 2% of patients included CRS, COVID-19 infection, sepsis, and tumor flare. Fatal adverse reactions occurred in 5% of patients from COVID-19 infection (3.4%), sepsis (1.4%), and delirium (0.6%). Adverse reactions led to permanent discontinuation of COLUMVI in 7% of patients, including from infection, delirium, neutropenia, and CRS. Adverse reactions led to dose interruptions of COLUMVI in 19% of patients, most frequently (≥ 2%) from neutropenia and thrombocytopenia. The most common (≥ 20%) adverse reactions, excluding laboratory terms, were CRS, musculoskeletal pain, rash, and fatigue. The most common Grade 3 to 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, phosphate decreased, neutrophil count decreased, uric acid increased, and fibrinogen decreased. Table 9 summarizes adverse reactions observed in Study NP30179. Table 9: Select Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory LBCL Who Received COLUMVI in Study NP30179 Adverse Reactions COLUMVI N=145 All grades (%) Grade 3 or 4 (%) The table includes a combination of grouped and ungrouped terms. Adverse reactions were graded using NCI CTCAE version 4.03, with the exception of CRS, which was graded per ASTCT consensus criteria in most cases. Immune system disorders Cytokine release syndrome 70 4.1 Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes musculoskeletal pain, back pain, bone pain, flank pain, myalgia, neck pain, and pain in extremity. 21 2.1 General disorders Fatigue Includes fatigue and asthenia. 20 1.4 Pyrexia 16 0 Edema Includes edema, edema peripheral, swelling face, and face edema. 10 0 Skin and subcutaneous tissue disorders Rash Includes rash, rash pruritic, rash maculo-papular, dermatitis, dermatitis acneiform, dermatitis exfoliative, erythema, palmar erythema, pruritus, and rash erythematous. 20 1.4 Gastrointestinal disorders Constipation 14 0 Diarrhea 14 0 Nausea 10 0 Abdominal pain Includes abdominal pain, abdominal discomfort, and abdominal pain upper. 10 0 Neoplasms Tumor flare 12 2.8 Neurologic Disorders Headache 10 0 Clinically relevant adverse reactions occurring in < 10% of patients who received COLUMVI included infusion-related reaction, peripheral neuropathy, pneumonia, mental status changes, vomiting, tumor lysis syndrome, febrile neutropenia, upper respiratory tract infection, sepsis, herpes zoster infection, gastrointestinal hemorrhage, tremor, myelitis, and colitis. Table 10 summarizes laboratory abnormalities in Study NP30179. Table 10: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Relapsed or Refractory LBCL Who Received COLUMVI in Study NP30179 Laboratory Abnormality COLUMVI The denominator used to calculate the rate varied from 137 to 145 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Lymphocytes decreased 90 83 Hemoglobin decreased 72 8 Neutrophils decreased 56 26 Grade 4 neutrophil decrease occurred in 9% of patients. Platelets decreased 56 8 Chemistry Fibrinogen decreased 84 21 Phosphate decreased 69 28 Sodium decreased 49 7 Calcium decreased 48 2.1 Gamma-glutamyl transferase increased 33 9 Potassium decreased 32 6 Uric acid increased 23 23

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 [see Clinical Pharmacology (12.2) ] 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 [see Warnings and Precautions (5.1) ] .

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.