LUNSUMIO™ (mosunetuzumab-axgb) is a T-cell engaging bispecific antibody designed to target both CD20 on B cells and CD3 on cytotoxic T cells.

Indication
LUNSUMIO (mosunetuzumab-axgb) is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

This indication is approved under accelerated approval based on response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

BOXED WARNING
Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LUNSUMIO. Initiate treatment with the LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Withhold LUNSUMIO until CRS resolves or permanently discontinue based on severity.

Please see the LUNSUMIO full Prescribing Information and the end of this video for additional Important Safety Information, including BOXED WARNING.

T cells are immune cells that survey their environment to identify foreign entities and abnormal cells, including virally infected or cancerous cells, in order to destroy them.

When a T cell encounters and recognizes an abnormal cell, an adaptive immune response is triggered. Upon T-cell activation, a special interface known as the immunologic synapse forms between the 2 cells.

Formation of the synapse allows the T cell to exert its cytotoxic activity.

Resistance mechanisms employed by cancer cells may allow them to evade T-cell adaptive response. LUNSUMIO aims to redirect T cells to recognize cancer cells but may also harm healthy cells.

LUNSUMIO is a fully humanized bispecific antibody…

...that has two Fab regions. It is designed for one of its regions to target a B-cell-specific protein called CD20, while the other targets CD3 on the surface of T cells.

Preclinical data suggest that LUNSUMIO induces the activation of T cells...

...by simultaneously binding to CD20, a protein expressed specifically on the surface of B cells, and CD3, a part of the T-cell receptor expressed on the surface of T cells.

When LUNSUMIO activates a T cell, an immunologic synapse may be formed between bound T and B cells, resulting in the secretion of perforin and granzymes by the T cell.

Perforin subsequently creates large transmembrane pores on the surface of the target B cell, allowing granzymes to enter the cell.  

The granzymes initiate a series of biochemical reactions, resulting in programmed cell death, also known as apoptosis, of the B cell.

Important Safety Information

BOXED WARNING
Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LUNSUMIO. Initiate treatment with the LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Withhold LUNSUMIO until CRS resolves or permanently discontinue based on severity.

Warnings and Precautions
Cytokine Release Syndrome (CRS)
LUNSUMIO can cause CRS, including serious or life-threatening reactions.

CRS occurred in 39% of patients who received LUNSUMIO at the recommended dose in the clinical trial, with Grade 1 CRS occurring in 28%, Grade 2 in 15%, Grade 3 in 2%, and Grade 4 in 0.5% of patients. Recurrent CRS occurred in 11% of patients. Most patients experienced CRS following doses of 1 mg on Cycle 1 Day 1 (15%), 2 mg on Cycle 1 Day 8 (5%), and 60 mg on Cycle 1 Day 15 (33%). Five percent of patients experienced CRS after receiving 60 mg on Cycle 2 Day 1 with 1% of patients experiencing CRS following subsequent doses of LUNSUMIO.

The median time to onset of CRS from the start of administration in Cycle 1 Day 1 was 5 hours (range: 1 hour to 3 days), Cycle 1 Day 8 was 28 hours (range: 5 hours to 3 days), Cycle 1 Day 15 was 25 hours (range: 0.1 hours to 16 days), and Cycle 2 Day 1 was 46 hours (range: 12 hours to 3 days). The median duration of CRS was 3 days (range: 1 to 29 days).

Clinical signs and symptoms of CRS included, but were not limited to, fever, chills, hypotension, tachycardia, hypoxia, and headache. Concurrent neurologic adverse reactions occurred in 6% of patients and included, but were not limited to, headache, confusional state, and anxiety. Initiate therapy according to LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Administer pretreatment medications to reduce the risk of CRS, ensure adequate hydration, and monitor patients following administration of LUNSUMIO accordingly.

At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold or permanently discontinue LUNSUMIO based on severity.

Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

Neurologic Toxicity
LUNSUMIO can cause serious neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

Neurologic toxicity occurred in 39% of patients who received LUNSUMIO at the recommended dose in the clinical trial, with Grade 3 neurologic toxicity occurring in 3% of patients. The most frequent neurologic toxicities were headache (21%), peripheral neuropathy (13%), dizziness (11%), and mental status changes (6%, including confusional state, disturbance in attention, cognitive disorder, delirium, encephalopathy, and somnolence). ICANS was reported in 1% of patients (Grade 1: 0.5%, Grade 2: 0.5%) who received LUNSUMIO at the recommended dose in the clinical trial.

Coadministration of LUNSUMIO with other products that cause dizziness or mental status changes may increase the risk of neurologic toxicity.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient, consider neurology evaluation as appropriate, and provide supportive therapy based on severity; withhold or permanently discontinue LUNSUMIO based on severity and follow management recommendations.

Patients who experience neurologic toxicity such as tremors, dizziness, insomnia, severe neurotoxicity, or any other adverse reactions that impair consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

Infections
LUNSUMIO can cause serious or fatal infections. Among patients who received LUNSUMIO at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 17%, with Grade 3 or 4 infections in 14%, and fatal infections in 0.9% of patients. The most common Grade 3 or greater infections were pneumonia, sepsis, and upper respiratory tract infection.

Monitor patients for signs and symptoms of infection prior to and during treatment with LUNSUMIO and treat appropriately. LUNSUMIO should not be administered in the presence of active infection. Caution should be exercised when considering the use of LUNSUMIO in patients with a history of recurring or chronic infections (e.g., chronic, active Epstein-Barr Virus), with underlying conditions that may predispose to infections or who have had significant prior immunosuppressive treatment. Administer prophylactic antimicrobials according to guidelines. Withhold LUNSUMIO or consider permanent discontinuation of LUNSUMIO based on severity.

Cytopenias
LUNSUMIO can cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia. Among patients who received the recommended dosage in the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 38%, decreased hemoglobin in 19%, and decreased platelets in 12% of patients. Grade 4 decreased neutrophils occurred in 19% and decreased platelets in 5% of patients. Febrile neutropenia occurred in 2%.

Monitor complete blood counts throughout treatment. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue LUNSUMIO. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.

Tumor Flare
LUNSUMIO can cause serious or severe tumor flare. Among patients who received LUNSUMIO at the recommended dosage in the clinical trial, tumor flare occurred in 4% of patients. Manifestations included new or worsening pleural effusions, localized pain and swelling at the sites of lymphoma lesions, and tumor inflammation.

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. If compression or obstruction develops, institute standard treatment of these complications.

Embryo-Fetal Toxicity
Based on its mechanism of action, LUNSUMIO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating LUNSUMIO. Advise females of reproductive potential to use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.

Most Common Adverse Reactions
The most common (≥20%) adverse reactions were CRS (39%), fatigue (36%), rash (34%), pyrexia (24%), and headache (21%).

The most common Grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocyte count (92%), decreased phosphate (41%), increased glucose (40%), decreased neutrophil count (38%), increased uric acid (15%), decreased white blood cell count (22%), decreased hemoglobin (19%), and decreased platelets (12%).

Drug Interactions
LUNSUMIO causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP450 substrates. Increased exposure of CYP450 substrates is more likely to occur after the first dose of LUNSUMIO on Cycle 1 Day 1 and up to 14 days after the second 60 mg dose on Cycle 2 Day 1 and during and after CRS. Monitor for toxicity or concentrations of drugs that are CYP450 substrates where minimal concentration changes may lead to serious adverse reactions. Consult the concomitant CYP450 substrate drug prescribing information for recommended dosage modification.

Use in Specific Populations
Lactation
There is no information regarding the presence of mosunetuzumab-axgb in human milk, the effect on the breastfed child, or milk production. Because human IgG is present in human milk, and there is potential for mosunetuzumab-axgb absorption leading to B-cell depletion, advise women not to breastfeed during treatment with LUNSUMIO for 3 months after the last dose.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see the LUNSUMIO full Prescribing Information for additional Important Safety Information, including BOXED WARNING.