Talvey Drug Information

TALVEY is 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 and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Recommended Dosage

For subcutaneous injection. Administer pretreatment medications prior to each dose of TALVEY in the step-up dosing schedule. Administer TALVEY subcutaneously on a weekly or biweekly (every 2 weeks) dosing schedule according to Table 1 or Table 2.

Continue treatment until disease progression or unacceptable toxicity. Corticosteroid (oral or intravenous dexamethasone, 16 mg or equivalent) Antihistamines (oral or intravenous diphenhydramine, 50 mg or equivalent) Antipyretics (oral or intravenous acetaminophen, 650 mg to 1,000 mg or equivalent) Administration of pretreatment medications may be required for subsequent doses for patients who repeat doses within the TALVEY step-up dosing schedule due to dose delays (see Table 3 or Table 4 ) or for patients who experienced CRS (see Table 5 ).

Dosage Delays If a dose of TALVEY is delayed, restart therapy based on the recommendations in Table 3 and Table 4 and resume weekly or biweekly (every 2 weeks) dosing schedule accordingly; if a dose is delayed by more than 28 days for an adverse reaction, evaluate the benefit-risk of restarting TALVEY. Administer pretreatment medications prior to restarting TALVEY and monitor patients following administration of TALVEY. Table 3: Recommendations for Restarting TALVEY after Dose Delay – Weekly Dosing Schedule Last Dose Administered Time from Last Dose Administered TALVEY Recommendation Administer pretreatment medications prior to restarting TALVEY.

After restarting TALVEY, resume weekly dosing schedule accordingly. After restarting TALVEY, resume biweekly (every 2 weeks) dosing schedule accordingly. s Dose delays may be required to manage toxicities related to TALVEY. See Table 5, Table 6, and Table 7 for recommended actions for the management of CRS, ICANS, and neurologic toxicity.

See Table 8 for recommended dose modifications for other adverse reactions. Cytokine Release Syndrome (CRS) Identify CRS based on clinical presentation. Evaluate and treat other causes of fever, hypoxia, and hypotension.

If CRS is suspected, withhold TALVEY until CRS resolves or permanently discontinue based on severity, manage according to the recommendations in Table 5, consider further management per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.

Table 5: Recommendations for Management of CRS Withhold TALVEY until CRS resolves. See Table 3 and Table 4 for recommendations on restarting TALVEY after dose delays for adverse reactions. Administer pretreatment medication prior to next dose. °F (38°C) with either: Hypotension requiring multiple vasopressors (excluding vasopressin).

Or, oxygen requirement of positive pressure (e.g., continuous positive airway pressure, bilevel positive airway pressure, intubation, and mechanical ventilation) Permanently discontinue TALVEY. Neurologic Toxicity, including ICANS At the first sign of neurologic toxicity, including ICANS, withhold TALVEY and consider neurology evaluation. Rule out other causes of neurologic symptoms.

Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS. Manage ICANS and neurologic toxicity according to the recommendations in Table 6 and Table 7 and consider further management per current practice guidelines. Table 6: Recommendations for Management of ICANS Withhold TALVEY until ICANS resolves.

Grade 2 ICE score 3–6, or depressed level of consciousness: awakens to voice. Withhold TALVEY until ICANS resolves. Patients should be hospitalized for 48 hours following the next dose of TALVEY.

Grade 3 ICE score 0–2, (If ICE score is 0, but the patient is arousable (e.g., awake with global aphasia) and able to perform assessment) or depressed level of consciousness: awakens only to tactile stimulus, or seizures, either: any clinical seizure, focal or generalized, that resolves rapidly, or non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging. Grade 4 ICE score 0 (Patient is unarousable and unable to perform ICE assessment) or depressed level of consciousness: either: patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma, or seizures, either: life-threatening prolonged seizure (>5 minutes), or repetitive clinical or electrical seizures without return to baseline in between, or motor findings: deep focal motor weakness such as hemiparesis or paraparesis, or raised intracranial pressure/cerebral edema, with signs/symptoms such as: diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing's triad. Permanently discontinue TALVEY.

Table 7: Recommendations for Management of Withhold TALVEY until neurologic toxicity symptoms resolve or stabilize. Table 8: Recommended Provide supportive care. Preparation and Administration Administer TALVEY via subcutaneous injection by a healthcare provider.

TALVEY should be administered by a healthcare provider with adequate medical personnel and appropriate medical equipment to manage severe reactions, including CRS and neurologic toxicity, including ICANS. TALVEY 3 mg/1.5 mL (2 mg/mL) vial and TALVEY 40 mg/mL vial are supplied as ready-to-use solution for injection that do not need dilution prior to administration. Do not combine TALVEY vials of different concentrations to achieve treatment dose.

Use aseptic technique to prepare and administer TALVEY. Preparation Refer to the following reference tables for the preparation of TALVEY. Use Table 9 to determine total dose, injection volume, and number of vials required based on patient's actual body weight for the 1 Use Table 10 to determine total dose, injection volume, and number of vials required based on patient's actual body weight for the 4 Use Table 11 to determine total dose, injection volume, and number of vials required based on patient's actual body weight for the 2 Use Table 12 to determine total dose, injection volume, and number of vials required based on patient's actual body weight for the 4 Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Check that the TALVEY solution for injection is colorless to light yellow. Do not use if the solution is discolored, cloudy, or if foreign particles are present. Remove the appropriate strength TALVEY vial(s) from refrigerated storage and equilibrate to ambient temperature for at least 15 minutes.

Do not warm TALVEY in any other way. Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake.

Withdraw the required injection volume of TALVEY from the vial(s) into an appropriately sized syringe using a transfer needle. Each injection volume should not exceed 2 mL. Divide doses requiring greater than 2 mL equally into multiple syringes.

TALVEY is compatible with stainless steel injection needles and polypropylene or polycarbonate syringe material. Replace the transfer needle with an appropriately sized needle for injection. Administration Inject the required volume of TALVEY into the subcutaneous tissue of the abdomen (preferred injection site).

Alternatively, TALVEY may be injected into the subcutaneous tissue at other sites (e.g., thigh). If multiple injections are required, TALVEY injections should be at least 2 cm apart. Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact.

Any unused medicinal product or waste material should be disposed in accordance with local requirements. Storage The prepared syringes should be administered immediately. If immediate administration is not possible, store the TALVEY solution refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours followed by at room temperature of 15°C to 30°C (59°F to 86°F) for up to 24 hours.

Discard if stored for more than 24 hours refrigerated or more than 24 hours at room temperature. If stored in the refrigerator, allow the solution to come to room temperature before administration.

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.

Serious adverse reactions occurred in 47% of patients who received TALVEY. 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. 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 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

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 respectively.

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