Talvey Drug Information

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/Refractory Multiple Myeloma MonumenTAL-1 The safety of TALVEY was evaluated in 339 adult patients with relapsed or refractory multiple myeloma. Patients treated with the weekly dosing schedule received step-up doses of 0.01 mg/kg and 0.06 mg/kg of TALVEY followed by TALVEY 0.4 mg/kg subcutaneously weekly thereafter.

Patients treated with the biweekly (every 2 weeks) dosing schedule received step-up doses of 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg (0.75 times the recommended step-up dose 3) followed by TALVEY 0.8 mg/kg subcutaneously every 2 weeks thereafter. The duration of exposure for the 0.4 mg/kg weekly regimen was 5.9 (range: 0.0 to 25.3) months (N=186) and for the 0.8 mg/kg biweekly (every 2 weeks) regimen, it was 3.7 (range: 0.0 to 17.9) months (N=153). Serious adverse reactions occurred in 47% of patients who received TALVEY. Serious adverse reactions in ≥ 2% of patients included CRS (13%), bacterial infection (8%) including sepsis, pyrexia (4.7%), ICANS (3.8%), COVID-19 (2.7%), neutropenia (2.1%), and upper respiratory tract infection (2.1%). Fatal adverse reactions occurred in 3.2% of patients who received TALVEY, including COVID - 19 (0.6%), dyspnea (0.6%), general physical health deterioration (0.6%), bacterial infection (0.3%) including sepsis, basilar artery occlusion (0.3%), fungal infection (0.3%), infection (0.3%), and pulmonary embolism (0.3%). Permanent discontinuation of TALVEY due to an adverse reaction occurred in 9% of patients. Adverse reactions which resulted in permanent discontinuation of TALVEY in > 1% of patients included ICANS. Dosage interruptions of TALVEY due to an adverse reaction occurred in 56% of patients.

Adverse reactions which required dosage interruption in > 5% of patients included pyrexia (15%), CRS (12%), upper respiratory tract infection (9%), COVID-19 (9%), bacterial infection (7%) including sepsis, neutropenia (6%), and rash (6%). The most common adverse reactions (≥ 20%) were pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥ 30%) were lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. Table 13 summarizes the adverse reactions in MonumenTAL-1. Table 13: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1 TALVEY N=339 System Organ Class Adverse Reaction Any Grade (%) Grade 3 or 4 (%) Adverse reactions were graded based on CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria.

General disorders and administration site conditions Pyrexia Includes other related terms. 83

Only grade 3 adverse reactions occurred. Fatigue 37 3.5 Chills 19 0

Pain 18

Edema 14 0 Injection site reaction 13 0 Immune system disorders Cytokine

release syndrome 76

Gastrointestinal disorders Dysgeusia Dysgeusia: ageusia, dysgeusia, hypogeusia and taste disorder. Per

CTCAE v4.03, maximum toxicity grade for dysgeusia is 2 and maximum toxicity grade for dry mouth is 3. 70 0 Dry mouth 34 0 Dysphagia 23

Diarrhea 21 0.9 Stomatitis Stomatitis: cheilitis, glossitis, glossodynia, mouth ulceration, oral discomfort

oral mucosal erythema, oral pain, stomatitis, swollen tongue, tongue discomfort, tongue erythema, tongue edema and tongue ulceration. 18

Nausea 18 0 Constipation 16 0 Oral disorder Oral disorder: oral disorder

oral dysesthesia, oral mucosal exfoliation, oral toxicity and oropharyngeal pain. 12 0 Skin and subcutaneous tissue disorders Nail disorder Nail disorder: koilonychia, nail bed disorder, nail cuticle fissure, nail discoloration, nail disorder, nail dystrophy, nail hypertrophy, nail pitting, nail ridging, nail toxicity, onychoclasis, onycholysis and onychomadesis. 50 0 Skin disorder Skin disorder: palmar-plantar erythrodysesthesia syndrome, palmoplantar keratoderma, skin discoloration, skin exfoliation and skin fissures. 41

Rash Rash: dermatitis, dermatitis acneiform, dermatitis contact, dermatitis exfoliative, dermatitis exfoliative generalized

erythema, exfoliative rash, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, rash vesicular and stasis dermatitis. 38

Musculoskeletal and connective tissue disorders Musculoskeletal pain 43 3.2 Investigations Weight decreased

35

Infections and infestations Upper respiratory tract infection 22 2.7 Bacterial infection including

sepsis Bacterial infection including sepsis: bacteremia, bacterial prostatitis, carbuncle, cellulitis, citrobacter infection, clostridium difficile colitis, clostridium difficile infection, cystitis escherichia, cystitis klebsiella, diverticulitis, enterobacter bacteremia, escherichia pyelonephritis, escherichia sepsis, folliculitis, gastroenteritis escherichia coli, helicobacter gastritis, human ehrlichiosis, klebsiella bacteremia, klebsiella sepsis, moraxella infection, otitis media acute, pitted keratolysis, pneumococcal sepsis, pneumonia, pneumonia streptococcal, pseudomonal bacteremia, pyuria, renal abscess, salmonella sepsis, sepsis, septic shock, skin infection, staphylococcal bacteremia, staphylococcal infection, staphylococcal sepsis, streptococcal bacteremia, tooth abscess, tooth infection, urinary tract infection enterococcal, and urinary tract infection pseudomonal. Includes fatal outcome(s): COVID-19 (N=2), dyspnea (N=2), bacterial infection including sepsis (N=1), fungal infection (N=1). 19 9 COVID-19 11

Fungal infection Fungal infection: body tinea, candida infection, ear infection fungal, esophageal

candidiasis, fungal infection, fungal sepsis, fungal skin infection, genital candidiasis, onychomycosis, oral candidiasis, oral fungal infection, oropharyngeal candidiasis, tinea pedis, vulvovaginal candidiasis, and vulvovaginal mycotic infection. 10

Vascular disorders Hypotension 21 2.9 Nervous system disorders Headache 21 0.6 Encephalopathy

Encephalopathy: agitation, altered state of consciousness, amnesia, aphasia, bradyphrenia, confusional state, delirium, depressed level of consciousness, disorientation, encephalopathy, hallucination, lethargy, memory impairment, mood altered, restlessness, sleep disorder and somnolence. 15

Sensory neuropathy Sensory neuropathy: dysesthesia, hyperesthesia, hypoesthesia, hypoesthesia oral, immune-mediated neuropathy, neuralgia

neuropathy peripheral, paresthesia, peripheral sensory neuropathy, polyneuropathy, sciatica and vestibular neuronitis. 14 0 Motor dysfunction Motor dysfunction: dysarthria, dysgraphia, dysmetria, dysphonia, gait disturbance, muscle atrophy, muscle spasms, muscular weakness and tremor. 10

Metabolism and nutrition disorders Decreased appetite 19 1.2 Respiratory, thoracic and mediastinal

disorders Cough 17 0 Dyspnea 11

Hypoxia 10 1.5 Cardiac disorders Tachycardia 11 0.6 Clinically relevant adverse reactions

reported in <10% of patients who received TALVEY included ICANS and viral infection. Table 14 summarizes select laboratory abnormalities in MonumenTAL-1. Table 14: Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1 TALVEY The denominator used to calculate the rate varied from 326 to 338 based on the number of patients with a baseline value and at least one post-treatment value. Laboratory Abnormality Any Grade (%) Grade 3 or 4 (%) Laboratory toxicity grades are derived based on the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 4.03. Hematology Lymphocyte count decreased 90 80 White blood cell decreased 73 35 Hemoglobin decreased 67 30 Neutrophil count decreased 64 35 Platelet count decreased 62 22 Chemistry Albumin decreased 66

Alkaline phosphatase increased 49 1.5 Phosphate decreased 44 13 Gamma-glutamyl transferase increased

38 7 Alanine aminotransferase increased 33

Potassium decreased 31 4.4 Sodium decreased 31 6 Aspartate aminotransferase increased 31

3.3

For certain cytochrome P450 (CYP) substrates, minimal changes in the substrate concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with TALVEY. Talquetamab-tgvs causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur from initiation of the TALVEY step-up dosing schedule up to 14 days after the first treatment dose and during and after CRS .

Pregnancy Risk Summary Based on the mechanism of action, TALVEY may cause fetal harm when administered to a pregnant woman . There are no available data on the use of TALVEY in pregnant women to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with talquetamab-tgvs. Talquetamab-tgvs causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance.

Human immunoglobulin G (IgG) is known to cross the placenta; therefore, TALVEY 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.

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