Kimmtrak Drug Information

KIMMTRAK is indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.

Patient Selection

Select patients for treatment of unresectable or metastatic uveal melanoma with KIMMTRAK based on a positive HLA-A*02:01 genotyping test of a whole blood sample. Administer the first three infusions of KIMMTRAK in an appropriate healthcare setting by intravenous infusion over 15-20 minutes. Monitor patients during the infusion and for at least 16 hours after the infusion is complete.

If the patient does not experience Grade 2 or worse hypotension (requiring medical intervention) during or after the third infusion, administer subsequent doses in an appropriate ambulatory care setting, and monitor patients for a minimum of 30 minutes following each of these infusions.

Dosage Modifications for Adverse Reactions

No dosage reduction for KIMMTRAK is recommended. Dosage modifications for KIMMTRAK for adverse reactions are summarized in Table 1. Table 1: Dose Modifications for

Preparation and Administration Preparation A 2-step dilution process is required for preparation of the final KIMMTRAK dose for infusion. Use aseptic technique for dilution and preparation of intravenous infusion solutions. Visually inspect parenteral drug products and infusion bags for particulate matter and discoloration prior to administration, whenever solution and container permit.

Step 1: Preparation of the Infusion Bag To prevent adsorption of tebentafusp-tebn to the infusion bag and other components of the drug delivery system, prepare an Albumin (Human) in 0.9% Sodium Chloride Injection, USP solution as follows: Using a 1 mL syringe with graduations of 2 decimal places and a sterile needle, withdraw the calculated volume of Albumin (Human) into the syringe (see Table 2 below) and add to the 100 mL 0.9% Sodium Chloride Injection, USP bag constructed of polyolefins (PO) or polyvinyl chloride (PVC) to make a final Albumin (Human) concentration of 250 mcg/mL. Table 2: Examples of Albumin (Human) Concentration and Volumes Gently homogenize the prepared solution by completing the following steps: Invert the infusion bag so that the bag is upside down with the entry port positioned on top. Then tap the side of the port tubing to ensure that any residual solution is released into the bulk solution.

Mix the prepared solution by gently rotating the bag lengthwise 360 degrees from the inverted position at least 5 times. Do not shake the infusion bag. Repeat (i) and (ii) an additional three times.

Step 2- Preparation of KIMMTRAK Solution for Infusion Do not shake the KIMMTRAK vial. Discard the single-dose vial containing the unused portion of KIMMTRAK in accordance with local requirements. Do not prepare more than one dose from the vial.

Table 3: KIMMTRAK Volumes Required for Addition to the Infusion Bag Mix the infusion bag by following the same procedure outlined in Step 1b. Administration Immediately administer the diluted solution via intravenous infusion over 15-20 minutes through a dedicated intravenous line. A sterile, non-pyrogenic, low protein binding 0.2 micron in-line filter infusion set should be used.

Administer the entire contents of the KIMMTRAK infusion bag. Administer the prepared infusion bag within 4 hours from the time of preparation including the duration of infusion. During the 4-hour window, the KIMMTRAK infusion bag should remain at room temperature.

If not used immediately, store the KIMMTRAK infusion bag in a refrigerator at 2°C to 8°C (36°F to 46°F) and infuse within 24 hours from the time of preparation, which includes the storage time in the refrigerator, the time allowed for equilibration of the infusion bag to room temperature, and the duration of the infusion. Once removed from the refrigerator, do not refrigerate KIMMTRAK infusion bag again. Do not freeze.

Discard unused KIMMTRAK solution beyond the recommended storage time. Do not mix KIMMTRAK with other drugs or administer other drugs through the same intravenous line. Upon completion of KIMMTRAK infusion, flush the infusion line with adequate volume of sterile 0.9% Sodium Chloride Injection, USP to ensure that the entire contents of the infusion bag are administered.

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. First line metastatic uveal melanoma The safety of KIMMTRAK was evaluated in study IMCgp100-202, a randomized (2:1), open-label, active-controlled trial in patients who had not received prior systemic therapy for metastatic or advanced uveal melanoma. The median duration of exposure was 5.3 months (range: 0.3 to 33 months) in patients treated with KIMMTRAK.

Serious adverse reactions occurred in 28% of patients who received KIMMTRAK. One patient (0.4%) experienced a fatal adverse reaction (pulmonary embolism). Adverse reactions led to permanent discontinuation in 3.3% of patients who received KIMMTRAK.

Adverse reactions that led to permanent discontinuation of KIMMTRAK were anaphylactic reaction, brain edema, cytokine release syndrome, fatigue, hepatotoxicity, hypotension, and nausea (each 0.4%). Adverse reactions resulting in dosage interruption occurred in 25% of patients who received KIMMTRAK. Adverse reactions leading to dose reduction occurred in 5% of patients who received KIMMTRAK.

Adverse reactions which required dosage reduction in ≥ 2% of patients were cytokine release syndrome (2.4%), and rashes (2%). The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities in patient who received KIMMTRAK were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

Table 4 summarizes the adverse reactions observed in study IMCgp100-202. Table 4: Adverse Reactions (≥20%) in Patients with Metastatic Uveal Melanoma Who Received KIMMTRAK in Study IMCgp 0 Clinically relevant adverse reactions occurring in < 20% of patients who received KIMMTRAK included back pain, decreased appetite, constipation, hypertension, tachycardia or sinus tachycardia, dyspnea, paresthesia, dizziness, flushing, muscle spasms, myalgia, pain in extremity, alopecia, skin hyperpigmentation, influenza-like illness, oropharyngeal pain and night sweats. Table 5 summarizes the selected laboratory abnormalities observed in study IMCgp100-202.

Table 5: Selected Laboratory Abnormalities (≥ 10%) worsening from baseline in patients who received KIMMTRAK versus Investigator’s Choice 0

Pregnancy Risk Summary Based on the mechanism of action, KIMMTRAK may cause fetal harm when administered to a pregnant woman. There are no available data with KIMMTRAK in pregnant woman. No animal reproductive and developmental toxicity studies have been conducted with KIMMTRAK.

Molecules of similar molecular weight can cross the placenta resulting in fetal exposure. 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 Safety and efficacy of KIMMTRAK have not been established in pediatric patients.