Columvi

COLUMVI (glofitamab) injection is a sterile, preservative-free, colorless, clear solution supplied in single-dose vials for intravenous infusion.
Each mL of solution contains 1 mg glofitamab.
Glofitamab 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 has an approximate molecular weight of 197 kDa.
Excipients/Inactive Ingredients: Each mL of solution contains L-histidine (0.63 mg), L-histidine hydrochloride monohydrate (3.34 mg), L-methionine (1.49 mg), polysorbate 20 (0.5 mg), D-sucrose (82.15 mg), and Water for Injection, USP, at pH 5.5.

Pharmacology: Mechanism of Action: Glofitamab 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 causes T-cell activation and proliferation, secretion of cytokines, and the lysis of CD20-expressing B cells. Glofitamab showed anti-tumor activity in vivo in mouse models of DLBCL.
Pharmacodynamics: Circulating B Cell Count: Peripheral B cell counts decreased to undetectable levels (< 5 cells/microliter) in 86.5% of patients by Cycle 1 Day 7 after obinutuzumab pretreatment of 1,000 mg on Cycle 1 Day 1, and in 88.2% of patients by Cycle 1 Day 10 after the first glofitamab dose of 2.5 mg on Cycle 1 Day 8.
Cytokine Concentrations: Plasma concentrations of cytokines (IL-2, IL-6, IL-10, TNF-α, and IFN-γ) were measured and transient elevation of cytokines was observed at doses of 0.045 mg and above. After administration of the recommended dosage of COLUMVI, the highest elevation of cytokines was generally observed within 6 hours after the first glofitamab dose of 2.5 mg on Cycle 1 Day 8. The elevated cytokine levels generally returned to baseline within 48 hours after the first 30 mg dose on Cycle 2 Day 1.
Clinical Studies: Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma: The efficacy of COLUMVI was evaluated in Study NP30179 (NCT03075696), an open-label, multicenter, multicohort, single-arm clinical trial that included patients with relapsed or refractory LBCL after two or more lines of systemic therapy. 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 x ULN or CLcr ≥ 50 mL/min, and hepatic transaminases ≤ 3 x ULN. The trial excluded patients with active or previous CNS lymphoma or CNS disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic HSCT.
Following pretreatment with obinutuzumab on Cycle 1 Day 1, patients received COLUMVI by intravenous infusion, starting with a 2.5 mg step-up dose on Cycle 1 Day 8, followed by a 10 mg step-up dose on Cycle 1 Day 15, then 30 mg on Cycle 2 Day 1 and on Day 1 of each subsequent cycle. The cycle length was 21 days. COLUMVI was administered for up to 12 cycles unless patients experienced progressive disease or unacceptable toxicity.
The efficacy population consists of 132 patients with de novo DLBCL, NOS (80%) or LBCL arising from follicular lymphoma (20%) who received at least one dose of COLUMVI. The median age was 67 years (range: 21 to 90 years), 64% were male, 77% were White, 4.5% were Asian, 0.8% were Black or African American, 5% were Hispanic or Latino. The median number of prior lines of systemic therapy was 3 (range: 2 to 7). Most patients (83%) had refractory disease to the last therapy, 55% had primary refractory disease, 30% had received CAR-T cell therapy, and 19% had received autologous HSCT.
Efficacy was based on objective response rate (ORR) and duration of response (DOR), as determined by an Independent Review Committee (IRC) using the 2014 Lugano criteria.
Efficacy results are summarized in Table 1. The median time to first response was 42 days (range: 31 to 178 days). Among responders, the estimated median follow-up for DOR was 11.6 months. (See Table 1.)

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Pharmacokinetics: The pharmacokinetics of glofitamab was determined following pretreatment with a single dose of obinutuzumab of 1,000 mg and the pharmacokinetic parameters are presented as geometric mean (CV%) unless otherwise specified. Glofitamab exposure increased dose-proportionally over the dose range from 0.005 to 30 mg (0.000167 to 1 time the recommended treatment dosage). Glofitamab exposure parameters are summarized in Table 2 for the approved recommended dosage of COLUMVI. (See Table 2.)

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Distribution: The glofitamab total volume of distribution is 5.6 L (24%).
Elimination: At steady state, the glofitamab terminal half-life is 7.6 days (24%) and the clearance is 0.617 L/day (33%).
Metabolism: Glofitamab is expected to be metabolized into small peptides by catabolic pathways.
Specific Populations: No clinically significant changes in the pharmacokinetics of glofitamab were observed based on age (21 to 90 years), body weight (31 to 148 kg), sex, mild to moderate renal impairment (CLcr 30 to < 90 mL/min as estimated by Cockcroft-Gault formula) and mild hepatic impairment (total bilirubin > ULN to ≤ 1.5 x ULN or AST > ULN).
The effects of severe renal impairment (CLcr 15 to < 30 mL/min), end-stage renal disease (CLcr < 15 mL/min), or moderate to severe hepatic impairment (total bilirubin > 1.5 x ULN and any AST), and race/ethnicity on the pharmacokinetics of glofitamab are unknown.
Drug Interaction Studies: No clinical studies evaluating the drug interaction potential of glofitamab have been conducted.
Immunogenicity: The observed incidence of antidrug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the study described as follows with the incidence of ADA in other studies, including those of glofitamab.
During treatment in Study NP30179 (up to 9 months) [see Pharmacology: Pharmacodynamics: Clinical Studies: Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma as previously mentioned], using an enzyme-linked immunosorbent assay (ELISA), the incidence of anti-glofitamab antibody formation was 1.1% (5/448) in patients treated with COLUMVI. Because of the low occurrence of ADAs, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of glofitamab is unknown.
Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: No carcinogenicity or genotoxicity studies have been conducted with glofitamab.
Fertility studies have not been conducted with 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.

Important Dosing Information: Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
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 Modifications for Adverse Reactions as follows].
Ensure adequate hydration before administering COLUMVI.
Premedicate before each dose [see Recommended Premedication and Prophylactic Medications as follows].
Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing schedule in Table 3 with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS [see Recommended Premedication and Prophylactic Medications as follows].
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 Recommended Dosage as follows and Cytokine Release Syndrome under Precautions].
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 Recommended Dosage as follows and Cytokine Release Syndrome under Precautions].
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.
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 3) 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 3. Administer premedications for each dose of COLUMVI as described in Table 5 [see Recommended Premedication and Prophylactic Medications as follows].

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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 Cytokine Release Syndrome under Precautions]: 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 4.
Delayed or Missed Doses: If a dose of COLUMVI is delayed, restart therapy based on the recommendations made in Table 4, 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. (See Table 4.)

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Recommended Premedication and Prophylactic Medications: Premedication: Administer the following premedications to reduce the risk of CRS and infusion-related reactions [see Cytokine Release Syndrome under Precautions]. (See Table 5.)

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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 Clinical Trials Experience under Adverse Reactions].
Antiviral Prophylaxis: Before starting COLUMVI, consider initiation of antiviral prophylaxis to prevent herpes virus reactivation. Consider prophylaxis for cytomegalovirus infection in patients at increased risk [see Serious Infections under Precautions].
Pneumocystis jirovecii Pneumonia (PJP): Consider PJP prophylaxis prior to starting COLUMVI in patients at increased risk [see Serious Infections under Precautions].
Dosage Modifications for Adverse Reactions: No dosage reduction for COLUMVI is recommended.
Cytokine Release Syndrome: Identify CRS based on clinical presentation [see Cytokine Release Syndrome under Precautions]. 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 6 and current practice guidelines. Administer supportive care for CRS, which may include intensive care for severe or life-threatening cases. (See Table 6.)

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Neurologic Toxicity, Including ICANS: Management recommendations for neurologic toxicity, including ICANS, is summarized in Table 7. 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. (See Table 7.)

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Other Adverse Reactions: See Table 8.

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Preparation and Administration: 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.
Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed (see Table 9).
Dilution: Withdraw the volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection from the infusion bag according to Table 9 and discard.
Withdraw the required volume of COLUMVI from vial(s) using a sterile needle and syringe and dilute into the infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection according to Table 9 to a final concentration of 0.1 mg/mL to 0.6 mg/mL. Discard any unused portion left in the vial. (See Table 9.)

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Gently invert infusion bag to mix the solution, in order to avoid excessive foaming. Do not shake.
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 diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or non-PVC polyolefin. When diluted with 0.45% Sodium Chloride Injection, COLUMVI is compatible with intravenous infusion bags composed of PVC.
No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), PVC, or PE, and in-line filter membranes composed of polyethersulfone (PES) or polysulfone.
COLUMVI Administration: Administer COLUMVI as an intravenous infusion only through a dedicated infusion line that includes a sterile 0.2-micron in-line filter.
See Table 3 for duration of infusion. The maximum time for the administration of the diluted infusion solution may be extended up to 8 hours (see Table 6).
Do not mix COLUMVI with other drugs.

None.

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 [see Dosage & Administration and Precautions].

Cytokine Release Syndrome: COLUMVI can cause serious and fatal cytokine release syndrome (CRS) [see Clinical Trials Experience under Adverse Reactions].
Among 145 patients who received COLUMVI, CRS occurred in 70%, with Grade 1 CRS developing in 52% of all patients, Grade 2 in 14%, Grade 3 in 2.8%, and Grade 4 in 1.4%. The most common manifestations of CRS included fever, tachycardia, hypotension, chills, and hypoxia.
CRS occurred in 56% of patients after the 2.5 mg dose of COLUMVI, 35% after the 10 mg dose, 29% after the initial 30 mg target dose, and 2.8% after subsequent doses. With the first step-up dose of COLUMVI, the median time to onset of CRS (from the start of infusion) was 14 hours (range: 5 to 74 hours). CRS after any dose resolved in 98% of cases, with a median duration of CRS of 2 days (range: 1 to 14 days). Recurrent CRS occurred in 34% of all patients. CRS can first occur with the 10 mg dose; of 135 patients treated with the 10 mg dose of COLUMVI, 15 patients (11%) experienced their first CRS event with the 10 mg dose, of which 13 events were Grade 1, 1 event was Grade 2, and 1 event was Grade 3.
Administer COLUMVI in a facility equipped to monitor and manage CRS. Initiate therapy according to the COLUMVI step-up dosing schedule to reduce the risk of CRS, administer pretreatment medications, and ensure adequate hydration [see Recommended Premedication and Prophylactic Medications under Dosage & Administration]. Patients should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg step-up dose. Patients who experienced any grade CRS during the 2.5 mg step-up dose should be hospitalized during and for 24 hours after completion of the 10 mg step-up dose. For subsequent doses, patients who experienced Grade ≥ 2 CRS with the previous infusion should be hospitalized during and for 24 hours after the next COLUMVI infusion [see Important Dosing Information and Recommended Dosage under Dosage & Administration].
At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold or permanently discontinue COLUMVI based on severity [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Neurologic Toxicity: COLUMVI can cause serious and fatal neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity (ICANS) [see Clinical Trials Experience under Adverse Reactions].
Among 145 patients who received COLUMVI, the most frequent neurologic toxicities of any grade were headache (10%), peripheral neuropathy (8%), dizziness or vertigo (7%), and mental status changes (4.8%, including confusional state, cognitive disorder, disorientation, somnolence, and delirium). Grade 3 or higher neurologic adverse reactions occurred in 2.1% of patients and included somnolence, delirium, and myelitis. Cases of ICANS of any grade occurred in 4.8% of patients.
Coadministration of COLUMVI with other products that cause dizziness or mental status changes may increase the risk of neurologic toxicity. Optimize concomitant medications and hydration to avoid dizziness or mental status changes. Institute fall precautions as appropriate.
Monitor patients for signs and symptoms of neurologic toxicity, evaluate, and provide supportive therapy; withhold or permanently discontinue COLUMVI based on severity [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Evaluate patients who experience neurologic toxicity such as tremors, dizziness, or adverse reactions that may impair cognition or consciousness promptly, including potential neurology evaluation. Advise affected patients to refrain from driving and/or engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurologic toxicity fully resolves.
Serious Infections: COLUMVI can cause serious or fatal infections [see Clinical Trials Experience under Adverse Reactions].
Serious infections were reported in 16% of patients, including Grade 3 or 4 infections in 10%, and fatal infections in 4.8% of patients. Grade 3 or higher infections reported in ≥ 2% of patients were COVID-19 infection (6%), including COVID-19 pneumonia, and sepsis (4.1%). Febrile neutropenia occurred in 3.4% of patients.
COLUMVI should not be administered to patients with an active infection. Administer antimicrobial prophylaxis according to guidelines. Monitor patients before and during COLUMVI treatment for infection and treat appropriately. Withhold or consider permanent discontinuation of COLUMVI based on severity [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Tumor Flare: COLUMVI can cause serious tumor flare [see Clinical Trials Experience under Adverse Reactions]. Manifestations include localized pain and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural effusions.
Tumor flare was reported in 12% of patients who received COLUMVI, including Grade 2 tumor flare in 4.8% of patients and Grade 3 tumor flare in 2.8%. Recurrent tumor flare occurred in two (12%) of the affected patients. Most tumor flare events occurred during Cycle 1, with a median time to first onset of 2 days (range: 1 to 16 days) after the first dose of COLUMVI. The median duration was 3.5 days (range: 1 to 35 days).
Patients with bulky tumors or disease located in close proximity to airways or a vital organ should be monitored closely during initial therapy. Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment. Withhold COLUMVI until tumor flare resolves [see Dosage Modifications for Adverse Reactions under Dosage & Administration].
Embryo-Fetal Toxicity: Based on its mechanism of action, COLUMVI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with COLUMVI and for 1 month after the last dose [see Pregnancy and Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
Use in Children: The safety and efficacy of COLUMVI in pediatric patients have not been established.
Use in the Elderly: Of the 145 patients with relapsed or refractory LBCL who received COLUMVI in study NP30179, 55% were 65 years of age or older, and 23% were 75 years of age or older. There was a higher rate of fatal adverse reactions, primarily from COVID-19, in patients 65 years of age or older compared to younger patients [see Clinical Trials Experience under Adverse Reactions]. No overall differences in efficacy were observed between patients 65 years of age or older and younger patients.

Pregnancy: Risk Summary: Based on its mechanism of action COLUMVI may cause fetal harm when administered to a pregnant woman [see Pharmacology: Mechanism of Action under Actions]. There are no available data on the use of COLUMVI in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with glofitamab.
Glofitamab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on expression of CD20 on B cells and the finding of B-cell depletion in non-pregnant animals, glofitamab can cause B-cell lymphocytopenia in infants exposed to glofitamab in-utero. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, COLUMVI has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Lactation: Risk Summary: There are no data on the presence of glofitamab in human milk or the effects on the breastfed child or milk production. Because human IgG is present in human milk, and there is potential for glofitamab absorption leading to B-cell depletion, advise women not to breastfeed during treatment with COLUMVI and for 1 month after the last dose of COLUMVI.
Females and Males of Reproductive Potential: COLUMVI may cause fetal harm when administered to a pregnant woman [see Pregnancy as previously mentioned].
Pregnancy Testing: Verify pregnancy status in females of reproductive potential prior to initiating COLUMVI.
Contraception: Females: Advise female patients of reproductive potential to use effective contraception during treatment with COLUMVI and for 1 month after the last dose of COLUMVI [see Pregnancy as previously mentioned].

The following clinically significant adverse reactions are described in Precautions: Cytokine Release Syndrome; Neurologic Toxicity; Serious Infections; Tumor Flare.
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 Pharmacology: Pharmacodynamics: Clinical Studies: Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma under Actions]. 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 x upper limit of normal (ULN) or creatinine clearance (CLcr) ≥ 50 mL/min, and hepatic transaminases ≤ 3 x 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 10 summarizes adverse reactions observed in Study NP30179. (See Table 10.)

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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, and myelitis.
Table 11 summarizes laboratory abnormalities in Study NP30179. (See Table 11.)

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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 causes the release of cytokines [see Pharmacology: Pharmacodynamics under Actions] 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 Cytokine Release Syndrome under Precautions].

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.

Advise the patient to read the Medication Guide.
Cytokine Release Syndrome: Inform patients of the risk of CRS. Advise patients to seek immediate medical attention if they experience signs and symptoms of CRS (fever, hypoxia, hypotension, chills and tachycardia) [see Precautions].
Provide patients with the Patient Wallet Card that they should carry with them at all times. This card describes symptoms of CRS which, if experienced, should prompt the patient to seek immediate medical attention.
Neurologic Toxicity: Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, headache, peripheral neuropathy, dizziness, or mental status changes. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity. Advise patients who experience neurologic toxicity that impairs consciousness to refrain from driving or operating heavy or potentially dangerous machinery until neurologic toxicity resolves [see Precautions].
Serious Infections: Advise patients that COLUMVI can cause serious infections. Advise patients to notify their healthcare provider immediately if they develop any signs of infection (e.g., fever, chills, weakness) [see Precautions].
Tumor Flare: Inform patients of the potential risk of tumor flare reaction and to report any signs and symptoms associated with this event (e.g., localized pain and swelling) to their healthcare provider for evaluation [see Precautions].
Embryo-Fetal Toxicity: Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential to use effective contraception during treatment with COLUMVI and for 1 month after the last dose [see Precautions and Use in Pregnancy & Lactation].
Advise women not to breastfeed while receiving treatment with COLUMVI and for 1 month after the last dose [see Use in Pregnancy & Lactation].

Targeted Cancer Therapy

L01FX28 - glofitamab ; Belongs to the class of other monoclonal antibodies and antibody drug conjugates. Used in the treatment of cancer.

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