Monjuvi Drug Information

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in other clinical trials of another drug and may not reflect the rates observed in practice. Relapsed or Refractory Diffuse Large B-cell Lymphoma The safety of MONJUVI in patients with relapsed or refractory DLBCL was evaluated in L-MIND. Patients (N = 81) received MONJUVI 12 mg/kg intravenously in combination with lenalidomide for a maximum of 12 cycles, followed by MONJUVI as monotherapy until disease progression or unacceptable toxicity as follows: Cycle 1: Days 1, 4, 8, 15, and 22 of the 28-day cycle; Cycles 2 and 3: Days 1, 8, 15, and 22 of each 28-day cycle; Cycles 4 and beyond: Days 1 and 15 of each 28-day cycle. Among patients who received MONJUVI, 57% were exposed for 6 months or longer, 42% were exposed for greater than one year, and 24% were exposed for greater than two years.

Serious adverse reactions occurred in 52% of patients who received MONJUVI. Serious adverse reactions in ≥ 6% of patients included infections (26%), including pneumonia (7%) and febrile neutropenia (6%). Fatal adverse reactions occurred in 5% of patients who received MONJUVI, including cerebrovascular accident (1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%), and sudden death (1.2%). Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. The most frequent adverse reactions which resulted in permanent discontinuation of MONJUVI were infections (5%), nervous system disorders (2.5%), and respiratory, thoracic and mediastinal disorders (2.5%). Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruptions of MONJUVI due to an adverse reaction occurred in 65%. The most frequent adverse reactions which required a dosage interruption of MONJUVI were blood and lymphatic system disorders (41%) and infections (27%). The most common adverse reactions (≥ 20%) were neutropenia, respiratory tract infection, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, and decreased appetite. Table 4 summarizes the adverse reactions in L-MIND. Table 4: Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma Who Received MONJUVI in L-MIND Adverse Reaction MONJUVI in Combination with Lenalidomide (N = 81) All Grades (%) Grade 3 or 4 (%) Blood and lymphatic system disorders Neutropenia 51 49 Anemia 36 7 Thrombocytopenia 31 17 Febrile neutropenia 12 12 Infections Respiratory tract infection Respiratory tract infection includes lower respiratory tract infection, upper respiratory tract infection, respiratory tract infection, bronchitis, pneumonia, nasopharyngitis, and related terms. 51 12 Urinary tract infection Urinary tract infection includes urinary tract infection, urinary tract infection bacterial, and related terms. 17

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

38

Pyrexia 24 1.2 Peripheral edema 24 0 Gastrointestinal disorders Diarrhea 36 1.2

Constipation 17 0 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain lower, and abdominal pain upper. 15

Nausea 15 0 Vomiting 15 0 Respiratory, thoracic and mediastinal disorders Cough

26

Dyspnea 12 1.2 Metabolism and nutrition disorders Decreased appetite 22 0 Hypokalemia

19 6 Musculoskeletal and connective tissue disorders Back pain 19

Muscle spasms 15 0 Skin and subcutaneous tissue disorders Rash Rash includes

rash, rash maculopapular, rash pruritic, rash erythematous, and rash pustular. 15

Pruritus 10 1.2 Clinically relevant adverse reactions in < 10% of patients

with relapsed or refractory DLBCL who received MONJUVI in L-MIND were: Blood and lymphatic system disorders: lymphopenia (6%) General disorders and administration site conditions: infusion-related reaction (6%) Infections: sepsis (4.9%) Investigations: weight decreased (4.9%) Musculoskeletal and connective tissue disorders: arthralgia (9%), pain in extremity (9%), musculoskeletal pain (2.5%) Neoplasms: basal cell carcinoma (1.2%) Nervous system disorders: headache (9%), paresthesia (7%), dysgeusia (6%) Respiratory, thoracic and mediastinal disorders: nasal congestion (4.9%), exacerbation of chronic obstructive pulmonary disease (1.2%) Skin and subcutaneous tissue disorders: erythema (4.9%), alopecia (2.5%), hyperhidrosis (2.5%) Table 5 summarizes the laboratory abnormalities in L-MIND. Table 5: Select Laboratory Abnormalities (≥ 20%) Worsening from Baseline in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma Who Received MONJUVI in L-MIND Laboratory Abnormality MONJUVI in Combination with Lenalidomide The denominator used to calculate the rate was 74 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Chemistry Glucose increased 49 5 Calcium decreased 47

Gamma glutamyl transferase increased 34 5 Albumin decreased 26 0 Magnesium decreased

22 0 Urate increased 20 7 Phosphate decreased 20 5 Creatinine increased 20

Relapsed or Refractory Follicular Lymphoma

The safety of MONJUVI in patients with relapsed or refractory FL was evaluated in the inMIND trial. Patients received MONJUVI 12 mg/kg (N = 274) or placebo (N = 272) intravenously for a maximum of 12 cycles in combination with lenalidomide 20 mg (Days 1-21 of Cycles 1 to 12) and rituximab 375 mg/m 2 (Cycles 1 to 5). MONJUVI was administered as follows: Cycle 1 to 3: Days 1, 8, 15, and 22 of each 28-day cycle; Cycles 4 to 12: Days 1 and 15 of each 28-day cycle. In the MONJUVI arm, 54% of patients completed all 12 cycles.

The median age in that arm was 64 years (range: 36-88 years); 20% were age 75 years or older; 55% were male; 80% were White, 15% Asian, and 0.4% Black. In the MONJUVI arm, serious adverse reactions occurred in 33% of patients, including serious infections in 24% of patients (including pneumonia and COVID-19 infection). Other serious adverse reactions in ≥ 2% of patients included renal insufficiency (3.3%), second primary malignancies (2.9%), and febrile neutropenia (2.6%). Fatal adverse reactions occurred in 1.5% of patients, including from COVID‑19, sepsis, and adenocarcinoma. Adverse reactions led to permanent discontinuation of MONJUVI in 11% of patients and dosage interruptions in 74%. The most frequent adverse reactions leading to dosage interruptions of MONJUVI were neutropenia (37% of all patients), COVID-19 (22%), pneumonia (11%), and infusion-related reaction (8%). The most common adverse reactions (≥ 20%) in recipients of MONJUVI, excluding laboratory abnormalities, were respiratory tract infections (including COVID-19 infection and pneumonia), diarrhea, rash, fatigue, constipation, musculoskeletal pain, and cough.

The most common Grade 3 or 4 laboratory abnormalities (≥ 20%) were decreased neutrophils and decreased lymphocytes. Table 6 summarizes the adverse reactions in inMIND. Adverse reactions occurring at least 5% more frequently in the MONJUVI arm included COVID-19 infection, pneumonia, diarrhea, pruritus, fatigue, musculoskeletal pain, and mucositis. Table 6: Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory Follicular Lymphoma Who Received MONJUVI in inMIND Adverse Reaction MONJUVI in Combination with Lenalidomide and Rituximab (N = 274) Placebo in Combination with Lenalidomide and Rituximab (N = 272) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Infections Respiratory tract infection 56 18 56 9 COVID-19 infection Includes COVID-19, COVID-19 pneumonia, and coronavirus test positive. 34 Includes 2 cases in each arm with fatal outcome. 10 24

Pneumonia Includes pneumonia

COVID-19 pneumonia, pneumonia fungal, Pneumocystis jirovecii pneumonia, and other types of pneumonia. 18 14 11 Includes 3 cases with fatal outcome, including 2 reported under COVID-19 infection. 7 Upper respiratory tract infection Includes upper respiratory tract infection, nasopharyngitis, sinusitis, laryngitis, and related terms. 17 1.1 22

Gastrointestinal disorders Diarrhea 38 0.7 28 1.8 Constipation 29 0.7 25 0

Nausea 18 0.4 14

Abdominal pain 13 0 18 2.2 Skin and subcutaneous tissue disorders Rash

Includes rash, urticaria, dermatitis, drug eruption, and related terms. 37 3.6 33

Pruritus 16 0.4 10 0 General disorders Fatigue Includes fatigue and asthenia.

34 2.9 25

Pyrexia 19 1.8 16 2.2 Mucositis Includes oropharyngeal pain, stomatitis, mucosal inflammation

mouth ulceration, odynophagia, aphthous ulcer, esophageal pain, and related terms. 17 0.4 11 0 Edema Includes edema, peripheral edema, pulmonary edema, generalized edema, and related terms. 11 0.7 17

Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes back pain, pain in

extremity, myalgia, bone pain, neck pain, spinal pain, limb discomfort, musculoskeletal chest pain, musculoskeletal discomfort, and sacral pain. 24 0.4 16

Muscle contracture Includes muscle spasms and muscle contractions involuntary. 18 0 19

0 Respiratory, thoracic and mediastinal disorders Cough 21 0 19 0 Procedural complications Infusion-related reaction Includes infusion-related reaction and cytokine release syndrome. 16 0.7 16

Nervous system disorders Peripheral neuropathy Includes peripheral neuropathy, paresthesia, peripheral sensory neuropathy

neuralgia, dysesthesia, hyperesthesia, and peripheral motor neuropathy. 12 0 11

Headache 10 0.4 7 0 Metabolism and nutrition disorders Decreased appetite 10

0 9

The table includes a combination of grouped and ungrouped terms. Adverse reactions

were graded using NCI CTCAE version

In the

MONJUVI arm, clinically relevant adverse reactions in < 10% of patients with relapsed or refractory FL included thrombosis, febrile neutropenia, second primary malignancy, sepsis, interstitial lung disease, and tumor lysis syndrome. Table 7 summarizes the laboratory abnormalities in inMIND. Grade 4 laboratory abnormalities in > 1% of patients included neutrophils decreased (19%), platelets decreased (4%) and lymphocytes decreased (1.8%). Table 7: Select Laboratory Abnormalities (> 20%) Worsening from Baseline in Patients with Relapsed or Refractory Follicular Lymphoma Who Received MONJUVI in inMIND Laboratory Abnormality MONJUVI in Combination with Lenalidomide and Rituximab The denominator used to calculate the rate varied from 268 - 274 based on the number of patients with a baseline value and at least 1 post-treatment value. Placebo in Combination with Lenalidomide and Rituximab All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Neutrophils decreased 75 48 71 44 Hemoglobin decreased 60 9 54 7 Lymphocytes decreased 57 22 51 19 Platelets decreased 40 8 43 9 Chemistry Alanine aminotransferase increased 47 1.5 42

Pregnancy Risk Summary Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman . There are no available data on MONJUVI use in pregnant women to evaluate for a drug-associated risk. Animal reproductive toxicity studies have not been conducted with tafasitamab-cxix. 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.

MONJUVI is administered in combination with lenalidomide, as well as in combination with lenalidomide and rituximab for up to 12 cycles. Lenalidomide can cause embryo-fetal harm and is contraindicated for use in pregnancy. Refer to the lenalidomide prescribing information for additional information.

Lenalidomide is only available through a REMS program. Clinical Considerations Fetal/Neonatal Adverse Reactions Immunoglobulin G (IgG) monoclonal antibodies are transferred across the placenta. Based on its mechanism of action, MONJUVI may cause depletion of fetal CD19 positive immune cells.

Defer administering live vaccines to neonates and infants exposed to tafasitamab-cxix in utero until a hematology evaluation is completed. Data Animal Data Animal reproductive studies have not been conducted with tafasitamab-cxix. Tafasitamab-cxix is an IgG antibody and thus has the potential to cross the placental barrier permitting direct fetal exposure and depleting fetal B lymphocytes.

Pediatric Use The safety and effectiveness of MONJUVI in pediatric patients have not been established.