Important Safety Information For

• TECVAYLI^®

  INDICATION AND USAGE

  TECVAYLI^® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

  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 confirmatory trial(s).

  IMPORTANT SAFETY INFORMATION

  WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

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

  Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI^®. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI^® until neurologic toxicity resolves or permanently discontinue based on severity.

  TECVAYLI^® is available only through a restricted program called the TECVAYLI^® and TALVEY™ Risk Evaluation and Mitigation Strategy (REMS).

  WARNINGS AND PRECAUTIONS

  Cytokine Release Syndrome - TECVAYLI^® can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI^® at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI^®. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

  Initiate therapy according to TECVAYLI^® step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI^® accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI^® based on severity.

  TECVAYLI^® is available only through a restricted program under a REMS.

  Neurologic Toxicity including ICANS - TECVAYLI^® can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

  In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI^® at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI^®.

  In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI^® at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI^®. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

  Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI^® based on severity per recommendations and consider further management per current practice guidelines.

  Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI^® step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

  TECVAYLI^® is available only through a restricted program under a REMS.

  TECVAYLI^® and TALVEY™ REMS - TECVAYLI^® is available only through a restricted program under a REMS called the TECVAYLI^® and TALVEY™ REMS because of the risks of CRS and neurologic toxicity, including ICANS.

  Hepatotoxicity - TECVAYLI^® can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

  Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

  Infections - TECVAYLI^® can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%. Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI^® and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

  Monitor immunoglobulin levels during treatment with TECVAYLI^® and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

  Neutropenia - TECVAYLI^® can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

  Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI^® based on severity.

  Hypersensitivity and Other Administration Reactions - TECVAYLI^® can cause both systemic administration-related and local injection-site reactions. Systemic Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

  Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI^® 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 TECVAYLI^® and for 5 months after the last dose.

  ADVERSE REACTIONS

  The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

  Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI^®.

  cp-322928v3

  INDICATION