Lunsumio Drug Information

Follicular Lymphoma

LUNSUMIO 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 rate . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

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. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to LUNSUMIO as a single agent in GO29781 in 218 patients with hematologic malignancies in an open-label, multicenter, multi-cohort study. Patients received step-up doses of 1 mg on Cycle 1 Day 1 and 2 mg on Cycle 1 Day 8, followed by 60 mg on Cycle 1 Day 15, and 60 mg on Cycle 2 Day 1, then 30 mg every 3 weeks in subsequent cycles.

Each treatment cycle was 21 days. Among 218 patients who received LUNSUMIO, 52% were exposed for at least 8 cycles and 8% were exposed for 17 cycles. In this pooled safety population, 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%), decreased hemoglobin (19%), increased uric acid (15%), and decreased platelets (12%). Relapsed or Refractory Follicular Lymphoma The safety of LUNSUMIO was evaluated in GO29781, an open-label, multicenter, multi-cohort study which included a cohort of 90 patients with relapsed or refractory follicular lymphoma (FL) . In this cohort, patients with relapsed or refractory FL were required to have received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent.

Patients received step-up doses of 1 mg on Cycle 1 Day 1 and 2 mg on Cycle 1 Day 8, followed by 60 mg on Cycle 1 Day 15 and 60 mg on Cycle 2 Day 1, then 30 mg every 3 weeks in subsequent cycles. A treatment cycle was 21 days. The median number of cycles was 8 (range: 1 to 17). In the relapsed or refractory FL cohort, 77% were exposed for at least 8 cycles and 12% were exposed for 17 cycles.

The median age was 60 years (range: 29 to 90 years), 61% were male, 82% were White, 4% were Black or African American, 9% were Asian, and 8% were Hispanic or Latino. Serious adverse reactions occurred in 47% of patients who received LUNSUMIO. Serious adverse reactions in ≥ 2% of patients included CRS, infection (including sepsis, pneumonia, urinary tract infection, EBV viremia, COVID-19, and upper respiratory tract infection), renal insufficiency, pyrexia, and tumor flare. Permanent discontinuation of LUNSUMIO due to an adverse reaction occurred in 3% of patients.

Adverse reactions resulting in permanent discontinuation of LUNSUMIO included CRS and EBV viremia. Dosage interruptions of LUNSUMIO due to an adverse reaction occurred in 37% of patients. Adverse reactions which required dosage interruption in ≥ 5% of patients included neutropenia, infection, and CRS. Table 8 summarizes the adverse reactions in patients with relapsed or refractory FL treated with LUNSUMIO in GO29781. Table 8. Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory FL Who Received LUNSUMIO Intravenous Infusion in GO29781 Adverse Reaction Adverse reactions were graded based on CTCAE Version 4.0, with the exception of CRS, which was graded per ASTCT 2019 criteria.

LUNSUMIO (N = 90) All Grades (%) Grade 3 or 4 (%) Immune system disorders Cytokine release syndrome 44

General disorders and administration site conditions Fatigue Fatigue includes fatigue, asthenia, and

lethargy. 42 0 Pyrexia 29

Only Grade 3 adverse reactions occurred. Edema Edema includes edema, edema peripheral

peripheral swelling, face edema, swelling face, pulmonary edema, fluid overload, and fluid retention. 17

Chills 13 1.1 Skin and subcutaneous tissue disorders Rash Rash includes rash

rash erythematous, exfoliative rash, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, erythema, palmar erythema, dermatitis, and dermatitis acneiform. 39

Pruritus 21 0 Dry skin 16 0 Skin exfoliation 10 0 Nervous

system Headache Headache includes headache and migraine. 32

Peripheral neuropathy Peripheral neuropathy includes peripheral neuropathy, peripheral sensory neuropathy, paresthesia, dysesthesia

hypoesthesia, burning sensation, and neuralgia. 20 0 Dizziness Dizziness includes dizziness and vertigo. 12 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes musculoskeletal pain, back pain, myalgia, musculoskeletal chest pain, and neck pain. 28

Arthralgia 11 0 Respiratory, thoracic, and mediastinal disorders Cough Cough includes cough

productive cough, and upper airway cough syndrome. 22 0 Dyspnea Dyspnea includes dyspnea and dyspnea exertional. 11

Gastrointestinal disorders Diarrhea 17 0 Nausea 17 0 Abdominal pain Abdominal pain

includes abdominal pain, lower abdominal pain, and abdominal discomfort. 12

Infections Upper respiratory tract infection Upper respiratory tract infection includes upper respiratory

tract infection, nasopharyngitis, sinusitis, and rhinovirus infection. 14

Urinary tract infection Urinary tract infection includes urinary tract infection and acute

pyelonephritis. 10

Psychiatric disorder Insomnia 12 0 Clinically relevant adverse reactions in < 10%

of patients who received LUNSUMIO included pneumonia, sepsis, COVID-19, EBV viremia, mental status changes, tumor lysis syndrome, renal insufficiency, anxiety, motor dysfunction (including ataxia, gait disturbance and tremor), tumor flare, and ICANS. Table 9 summarizes the laboratory abnormalities in patients with relapsed or refractory FL treated with LUNSUMIO in GO29781. Table 9. Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Relapsed or Refractory FL Who Received LUNSUMIO Intravenous Infusion in GO29781 Laboratory Abnormality LUNSUMIO The denominator used to calculate the rate varied from 72 to 90 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Lymphocyte count decreased 100 98 Hemoglobin decreased 68 12 Neutrophils decreased 58 40 Platelets decreased 46 10 Chemistry Phosphate decreased 78 46 Glucose increased 42 42 Aspartate aminotransferase increased 39

Gamma-glutamyl transferase increased 34 9 Magnesium decreased 34 0 Potassium decreased 33

6 Alanine aminotransferase increased 32 7 Uric acid increased 22 22

Effect of LUNSUMIO on CYP450 Substrates 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 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.

Pregnancy Risk Summary Based on the mechanism of action, LUNSUMIO may cause fetal harm when administered to a pregnant woman . There are no available data on the use of LUNSUMIO in pregnant women to evaluate for a drug-associated risk. No animal reproductive or developmental toxicity studies have been conducted with mosunetuzumab-axgb. Mosunetuzumab-axgb 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, mosunetuzumab-axgb can cause B-cell lymphocytopenia in infants exposed to mosunetuzumab-axgb in-utero. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, LUNSUMIO 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% – 4% and 15% – 20%, respectively.

Pediatric Use The safety and efficacy of LUNSUMIO have not been established in pediatric patients.