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

{ "type": "p", "children": [], "text": "KIMMTRAK is indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma." }

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 [see Clinical Studies (14)]. Information on FDA-approved tests is available at http://www.fda.gov/companiondiagnostics.

The recommended dosage of KIMMTRAK administered intravenously is:

Treat patients until unacceptable toxicity or disease progression occur.

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 [see Warnings and Precautions (5.1)].

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

Table 1: Dose Modifications for Adverse Reactions

<div class="scrollingtable"><table class="Noautorules" width="775"> <col align="left" width="20%"/> <col align="center" width="38%"/> <col align="center" width="42%"/> <tfoot> <tr> <td align="left" colspan="3"><span class="Sup">a</span> Based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (NCI CTCAEv4.03).</td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top"><span class="Bold">Adverse Reaction</span></td><td align="left" class="Lrule Rrule Toprule" valign="top"><span class="Bold">Severity</span></td><td align="left" class="Lrule Rrule Toprule" valign="top"><span class="Bold">KIMMTRAK Dosage Modifications</span></td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" rowspan="3" valign="top"><span class="Bold">Cytokine Release Syndrome (CRS)</span> <br/> <br/> <span class="Italics">[see <a href="#s_0501">Warnings and Precautions (5.1)</a>]</span></td><td align="left" class="Lrule Rrule Toprule" valign="top">Moderate defined as temperature ≥ 38°C with <ul class="Disc"> <li>Hypotension that responds to fluids (does not require vasopressors) or</li> <li>Hypoxia requiring low flow nasal canula (≤ 6 L/min) or blow-by oxygen</li> </ul> </td><td align="left" class="Lrule Rrule Toprule" valign="top"> <ul class="Disc"> <li>If hypotension and hypoxia do not improve within 3 hours or CRS worsens, escalate care and manage according to next higher level of severity</li> <li>For moderate CRS that is persistent (lasting 2-3 hours) or recurrent, administer corticosteroid premedication (e.g. dexamethasone 4 mg or equivalent) at least 30 minutes prior to next dose</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Severe defined as temperature ≥ 38°C with <ul class="Disc"> <li>Hemodynamic instability requiring a vasopressor (with or without vasopressin) or</li> <li>Worsening hypoxia or respiratory distress requiring high flow nasal canula (&gt; 6 L/min oxygen) or face mask</li> </ul> </td><td align="left" class="Lrule Rrule Toprule" valign="top"> <ul class="Disc"> <li>Withhold KIMMTRAK until CRS and sequelae have resolved </li> <li>Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)</li> <li>Resume KIMMTRAK at same dose level (i.e., do not escalate if severe CRS occurred during initial dose escalation; resume escalation once dosage is tolerated)</li> <li>For severe CRS, administer corticosteroid premedication (e.g. dexamethasone 4 mg or equivalent) at least 30 minutes prior to next dose</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Life threatening defined as temperature ≥ 38°C with <ul class="Disc"> <li>Hemodynamic instability requiring multiple vasopressors (excluding vasopressin)</li> <li>Worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure</li> </ul> </td><td align="left" class="Lrule Rrule Toprule" valign="top"> <ul class="Disc"> <li>Permanently discontinue KIMMTRAK</li> <li>Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" rowspan="2" valign="top"><span class="Bold">Skin Reactions</span> <br/> <br/> <span class="Italics">[see <a href="#s_0502">Warnings and Precautions (5.2)</a>]</span></td><td align="left" class="Lrule Rrule Toprule" valign="top">Grade 2 or 3<span class="Sup">a</span></td><td align="left" class="Lrule Rrule Toprule" valign="top"> <ul class="Disc"> <li>Withhold KIMMTRAK until ≤ Grade 1 or baseline</li> <li>Resume KIMMTRAK at same dose level (i.e., do not escalate if Grade 3 skin reactions occurred during initial dose escalation; resume escalation once dosage is tolerated)</li> <li>For persistent reactions not responding to oral steroids, consider intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top">Grade 4<span class="Sup">a</span></td><td align="left" class="Lrule Rrule Toprule" valign="top"> <ul class="Disc"> <li>Permanently discontinue KIMMTRAK</li> <li>Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" valign="top"><span class="Bold">Elevated Liver Enzymes</span> <br/> <br/> <span class="Italics">[see <a href="#s_0503">Warnings and Precautions (5.3)</a>]</span></td><td align="left" class="Lrule Rrule Toprule" valign="top">Grade 3 or 4<span class="Sup">a</span></td><td align="left" class="Lrule Rrule Toprule" valign="top"> <ul class="Disc"> <li>Withhold KIMMTRAK until ≤ Grade 1 or baseline.</li> <li>Resume KIMMTRAK at same dose level if the elevated liver enzymes occur in the setting of Grade 3 CRS; resume escalation if next administration is tolerated.</li> <li>If the elevated liver enzymes occur outside the setting of Grade 3 CRS <ul> <li>resume escalation if the current dose is less than 68 mcg, </li> <li>or resume at same dose level if dose escalation has completed</li> </ul> </li> <li>Administer intravenous corticosteroids if no improvement within 24 hours</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"><span class="Bold">Other Adverse Reactions</span> <br/> <br/> <span class="Italics">[see <a href="#s_0601">Adverse Reactions (6.1)</a>]</span></td><td align="left" class="Lrule Rrule Toprule" valign="top">Grade 3<span class="Sup">a</span></td><td align="left" class="Lrule Rrule Toprule" valign="top"> <ul class="Disc"> <li>Withhold KIMMTRAK until ≤ Grade 1 or baseline</li> <li>Resume KIMMTRAK at same dose level (i.e., do not escalate if other Grade 3 adverse reaction occurred during initial dose escalation; resume escalation once dosage is tolerated)</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top">Grade 4<span class="Sup">a</span></td><td align="left" class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Permanently discontinue KIMMTRAK</li> </ul> </td> </tr> </tbody> </table></div>

Preparation

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:

Step 2- Preparation of KIMMTRAK Solution for Infusion

Administration

Injection: 100 mcg/0.5 mL clear, colorless to slightly yellowish solution in a single-dose vial

{ "type": "p", "children": [], "text": "Injection: 100 mcg/0.5 mL clear, colorless to slightly yellowish solution in a single-dose vial" }

None.

{ "type": "p", "children": [], "text": "None." }

Cytokine release syndrome (CRS), which may be life threatening, occurred in patients receiving KIMMTRAK. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS (≥ Grade 2) occurred in 77% of patients in Study IMCgp100-202 who received KIMMTRAK [see Adverse Reactions (6.1)]. Among patients who received KIMMTRAK, 23% received systemic corticosteroids for at least 1 infusion, 8% received supplemental oxygen during at least 1 infusion, and 0.8% received a vasopressor for at least 1 infusion. CRS led to permanent discontinuation in 1.2% of patients.

In Study IMCgp100-202, 60% of patients experienced ≥ Grade 2 CRS with more than 1 infusion, with the median number of events being 2 (range 1 - 12). The majority (84%) of episodes of CRS started the day of infusion. Among cases that resolved, the median time to resolution of CRS was 2 days.

Ensure that healthcare providers administering KIMMTRAK have immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK [see Dosage and Administration (2.2)].

Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS [see Dosage and Administration (2.3)].

Skin reactions, including rash, pruritus, and cutaneous edema occurred in patients treated with KIMMTRAK. In study IMCgp100-202, skin reactions occurred in 91% of patients treated with KIMMTRAK, including Grade 2 (44%) and Grade 3 (21%) events. Skin reactions included rash (83%), pruritus (69%), erythema (25%), and cutaneous edema (27%) [see Adverse Reactions (6.1)].

The median time to onset of skin reactions was 1 day (range: 1 – 55 days). The median time to improvement to ≤ Grade 1 was approximately 6 days.

Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions [see Dosage and Administration (2.3)].

In Study IMCgp100-202, increases in alanine aminotransferase or aspartate aminotransferase were observed in 65% of patients treated with KIMMTRAK.

In patients experiencing ALT/AST elevations, 73% initially occurred within the first 3 infusions with KIMMTRAK. Most patients experiencing Grade 3 or 4 ALT/AST elevations had improvement to ≤ Grade 1 within 7 days. For events that were observed outside the setting of CRS, the median time to onset was 129 days. Grade 3 or greater elevations in liver enzymes outside the setting of CRS occurred in approximately 8% of patients.

Elevations in liver enzymes led to permanent discontinuation in 0.4% of patients receiving KIMMTRAK.

Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity [see Dosage and Administration (2.3)].

Based on the mechanism of action, KIMMTRAK 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 KIMMTRAK and for 1 week after the last dose [see Use in Specific Populations (8.1, 8.3)].

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 [see Clinical Studies (14)]. Patients received either KIMMTRAK administered at 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (N=245) or investigator’s choice treatment (N=111). 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. Serious adverse reactions occurring in ≥ 2% of patients were cytokine release syndrome (10%), rashes (4.5%), pyrexia (2.4%), and hypotension (2%). 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 which required dosage interruption in ≥ 2% of patients included fatigue (3.7%), lipase increased (2.9%), pyrexia (2.4%), alanine aminotransferase increase (2%), and aspartate aminotransferase increase (2%).

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 IMCgp100-202

<div class="scrollingtable"><table class="Noautorules" width="700"> <col align="left" width="35%"/> <col align="center" width="13%"/> <col align="center" width="13%"/> <col align="center" width="13%"/> <col align="center" width="13%"/> <tfoot> <tr> <td align="left" colspan="5"><span class="Sup">a</span> Represents algorithmic identification of CRS cases based on ASTCT grading criteria (Lee et al. 2019).<br/> <span class="Sup">b</span> Represents a composite of multiple related terms. </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Adverse Reactions</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">KIMMTRAK<br/>(N=245)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Investigator’s Choice (pembrolizumab, or ipilimumab, or dacarbazine)<br/>(N=111)</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All Grades<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 3 or 4<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All Grades<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 3 or 4<br/>(%</span>)</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Immune system disorders</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Cytokine release syndrome<span class="Sup">a</span></td><td align="center" class="Botrule Lrule Rrule Toprule">89</td><td align="center" class="Botrule Lrule Rrule Toprule">0.8</td><td align="center" class="Botrule Lrule Rrule Toprule">2.7</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Skin and subcutaneous tissue disorders</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Rash<span class="Sup">b</span></td><td align="center" class="Botrule Lrule Rrule Toprule">83</td><td align="center" class="Botrule Lrule Rrule Toprule">18</td><td align="center" class="Botrule Lrule Rrule Toprule">28</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Pruritus</td><td align="center" class="Botrule Lrule Rrule Toprule">69</td><td align="center" class="Botrule Lrule Rrule Toprule">4.5</td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Dry skin</td><td align="center" class="Botrule Lrule Rrule Toprule">31</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">3.6</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Skin Hypopigmentation<span class="Sup">b</span></td><td align="center" class="Botrule Lrule Rrule Toprule">28</td><td align="center" class="Botrule Lrule Rrule Toprule">NA</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">NA</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Erythema</td><td align="center" class="Botrule Lrule Rrule Toprule">24</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Hair color changes<span class="Sup">b</span></td><td align="center" class="Botrule Lrule Rrule Toprule">20</td><td align="center" class="Botrule Lrule Rrule Toprule">NA</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">NA</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">General disorders and administration site conditions</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Pyrexia</td><td align="center" class="Botrule Lrule Rrule Toprule">76</td><td align="center" class="Botrule Lrule Rrule Toprule">3.7</td><td align="center" class="Botrule Lrule Rrule Toprule">7</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Fatigue<span class="Sup">b</span></td><td align="center" class="Botrule Lrule Rrule Toprule">64</td><td align="center" class="Botrule Lrule Rrule Toprule">6</td><td align="center" class="Botrule Lrule Rrule Toprule">42</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Chills</td><td align="center" class="Botrule Lrule Rrule Toprule">48</td><td align="center" class="Botrule Lrule Rrule Toprule">0.4</td><td align="center" class="Botrule Lrule Rrule Toprule">3.6</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Edema<span class="Sup">b</span></td><td align="center" class="Botrule Lrule Rrule Toprule">45</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">10</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Gastrointestinal disorders</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Nausea</td><td align="center" class="Botrule Lrule Rrule Toprule">49</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td><td align="center" class="Botrule Lrule Rrule Toprule">26</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Abdominal pain<span class="Sup">b</span></td><td align="center" class="Botrule Lrule Rrule Toprule">45</td><td align="center" class="Botrule Lrule Rrule Toprule">2.9</td><td align="center" class="Botrule Lrule Rrule Toprule">33</td><td align="center" class="Botrule Lrule Rrule Toprule">3.6</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Vomiting</td><td align="center" class="Botrule Lrule Rrule Toprule">30</td><td align="center" class="Botrule Lrule Rrule Toprule">1.2</td><td align="center" class="Botrule Lrule Rrule Toprule">9</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Diarrhea</td><td align="center" class="Botrule Lrule Rrule Toprule">25</td><td align="center" class="Botrule Lrule Rrule Toprule">1.2</td><td align="center" class="Botrule Lrule Rrule Toprule">20</td><td align="center" class="Botrule Lrule Rrule Toprule">2.7</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Vascular disorders</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Hypotension</td><td align="center" class="Botrule Lrule Rrule Toprule">39</td><td align="center" class="Botrule Lrule Rrule Toprule">3.3</td><td align="center" class="Botrule Lrule Rrule Toprule">2.7</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Nervous system disorders</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Headache</td><td align="center" class="Botrule Lrule Rrule Toprule">31</td><td align="center" class="Botrule Lrule Rrule Toprule">0.4</td><td align="center" class="Botrule Lrule Rrule Toprule">10</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Musculoskeletal and connective tissue disorders</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Arthralgia</td><td align="center" class="Botrule Lrule Rrule Toprule">22</td><td align="center" class="Botrule Lrule Rrule Toprule">0.8</td><td align="center" class="Botrule Lrule Rrule Toprule">16</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> </tbody> </table></div>

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.

<div class="scrollingtable"><table class="Noautorules" width="700"> <caption> <span>Table 5: Selected Laboratory Abnormalities (≥ 10%) worsening from baseline in patients who received KIMMTRAK versus Investigator’s Choice</span> </caption> <col align="left" width="28%"/> <col align="center" width="18%"/> <col align="center" width="18%"/> <col align="center" width="18%"/> <col align="center" width="18%"/> <tfoot> <tr> <td align="left" colspan="5">Alk Phos = Alkaline Phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase<br/> <span class="Sup">a</span> The denominator used to calculate the rate varied from 242 to 245 for KIMMTRAK and 105 to 109 for IC based on the number of patients with a baseline value and at least one post-treatment value for the laboratory assessment. </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">KIMMTRAK</span><span class="Sup">a</span> <br/> <span class="Bold">(N=245)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Investigator’s Choice</span><span class="Sup">a</span><span class="Bold">(pembrolizumab, or ipilimumab, or dacarbazine)<br/>(N=111)</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grades 1-4 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grades 3-4 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grades 1-4 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grades 3-4 <br/>(%</span>)</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">HEMATOLOGY</span></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Lymphocyte count decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">91</td><td align="center" class="Botrule Lrule Rrule Toprule">56</td><td align="center" class="Botrule Lrule Rrule Toprule">26</td><td align="center" class="Botrule Lrule Rrule Toprule">1.8</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Hemoglobin decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">51</td><td align="center" class="Botrule Lrule Rrule Toprule">0.8</td><td align="center" class="Botrule Lrule Rrule Toprule">20</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Platelet count decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">16</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Neutrophil count decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">14</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">1.8</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">CHEMISTRY</span></td><td align="center" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"></td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Creatinine increased </td><td align="center" class="Botrule Lrule Rrule Toprule">87</td><td align="center" class="Botrule Lrule Rrule Toprule">0.4</td><td align="center" class="Botrule Lrule Rrule Toprule">73</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Glucose increased </td><td align="center" class="Botrule Lrule Rrule Toprule">66</td><td align="center" class="Botrule Lrule Rrule Toprule">3.3</td><td align="center" class="Botrule Lrule Rrule Toprule">39</td><td align="center" class="Botrule Lrule Rrule Toprule">4.6</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">AST increased </td><td align="center" class="Botrule Lrule Rrule Toprule">55</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">39</td><td align="center" class="Botrule Lrule Rrule Toprule">1.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">ALT increased </td><td align="center" class="Botrule Lrule Rrule Toprule">52</td><td align="center" class="Botrule Lrule Rrule Toprule">9</td><td align="center" class="Botrule Lrule Rrule Toprule">29</td><td align="center" class="Botrule Lrule Rrule Toprule">1.8</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Phosphate decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">51</td><td align="center" class="Botrule Lrule Rrule Toprule">11</td><td align="center" class="Botrule Lrule Rrule Toprule">20</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Albumin decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">47</td><td align="center" class="Botrule Lrule Rrule Toprule">2.1</td><td align="center" class="Botrule Lrule Rrule Toprule">14</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Calcium decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">45</td><td align="center" class="Botrule Lrule Rrule Toprule">1.6</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">1.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Lipase increased </td><td align="center" class="Botrule Lrule Rrule Toprule">37</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">28</td><td align="center" class="Botrule Lrule Rrule Toprule">6</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Magnesium decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">34</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Alk phos increased </td><td align="center" class="Botrule Lrule Rrule Toprule">34</td><td align="center" class="Botrule Lrule Rrule Toprule">2.9</td><td align="center" class="Botrule Lrule Rrule Toprule">36</td><td align="center" class="Botrule Lrule Rrule Toprule">1.8</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Sodium decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">30</td><td align="center" class="Botrule Lrule Rrule Toprule">2.9</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Potassium increased </td><td align="center" class="Botrule Lrule Rrule Toprule">29</td><td align="center" class="Botrule Lrule Rrule Toprule">1.6</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Bilirubin increased </td><td align="center" class="Botrule Lrule Rrule Toprule">27</td><td align="center" class="Botrule Lrule Rrule Toprule">4.1</td><td align="center" class="Botrule Lrule Rrule Toprule">14</td><td align="center" class="Botrule Lrule Rrule Toprule">7</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Amylase increased </td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">4.1</td><td align="center" class="Botrule Lrule Rrule Toprule">18</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Glucose decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">18</td><td align="center" class="Botrule Lrule Rrule Toprule">0.4</td><td align="center" class="Botrule Lrule Rrule Toprule">4.6</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Potassium decreased </td><td align="center" class="Botrule Lrule Rrule Toprule">17</td><td align="center" class="Botrule Lrule Rrule Toprule">0.8</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule">Calcium increased </td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">3.7</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> </tbody> </table></div>

Risk Summary

Based on the mechanism of action, KIMMTRAK may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. 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.

Risk Summary

There are no data on the presence of tebentafusp-tebn in human milk, the effect on the breastfed child, or the effects on milk production. Because tebentafusp-tebn may be excreted in human milk and because of the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with KIMMTRAK and for at least 1 week after the last dose.

KIMMTRAK may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

Pregnancy Testing

Verify pregnancy status in females of reproductive potential prior to initiating KIMMTRAK treatment.

Contraception

Females

Advise female of reproductive potential to use effective contraception during treatment and for 1 week following the last dose of KIMMTRAK [see Use in Specific Populations (8.1)].

Safety and efficacy of KIMMTRAK have not been established in pediatric patients.

Of the 245 patients with metastatic uveal melanoma treated with KIMMTRAK on IMCgp100-202, 47% were 65 years of age and older and 9% were 75 years of age and older. No overall differences in safety or efficacy were observed between patients ≥ 65 years of age compared to younger adult patients.

Tebentafusp-tebn is a bispecific gp100 peptide-HLA-directed T cell receptor CD3 T cell engager. Tebentafusp-tebn has an approximate molecular weight of 77 kDa. Tebentafusp-tebn is produced by recombinant DNA technology in Escherichia coli cells.

{ "type": "p", "children": [], "text": "Tebentafusp-tebn is a bispecific gp100 peptide-HLA-directed T cell receptor CD3 T cell engager. Tebentafusp-tebn has an approximate molecular weight of 77 kDa. Tebentafusp-tebn is produced by recombinant DNA technology in Escherichia coli cells." }

KIMMTRAK (tebentafusp-tebn) injection is supplied in a single-dose vial as a sterile, preservative-free, clear, colorless or slightly yellowish solution for intravenous administration by infusion.

{ "type": "p", "children": [], "text": "KIMMTRAK (tebentafusp-tebn) injection is supplied in a single-dose vial as a sterile, preservative-free, clear, colorless or slightly yellowish solution for intravenous administration by infusion." }

Each single-dose vial contains tebentafusp-tebn (100 mcg), citric acid monohydrate (0.95 mg), di-sodium hydrogen phosphate (2.91 mg), mannitol (5 mg), polysorbate 20 (0.1 mg) trehalose (25 mg), and water for injection, with a pH of 6.5.

{ "type": "p", "children": [], "text": "Each single-dose vial contains tebentafusp-tebn (100 mcg), citric acid monohydrate (0.95 mg), di-sodium hydrogen phosphate (2.91 mg), mannitol (5 mg), polysorbate 20 (0.1 mg) trehalose (25 mg), and water for injection, with a pH of 6.5." }

Tebentafusp-tebn is a bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor CD3 T cell engager. The TCR arm binds to a gp100 peptide presented by human leukocyte antigen-A*02:01 (HLA-A*02:01) on the cell surface of uveal melanoma tumor cells.

In vitro, tebentafusp-tebn bound to HLA-A*02:01-positive uveal melanoma cells and activated polyclonal T cells to release inflammatory cytokines and cytolytic proteins, which results in direct lysis of uveal melanoma tumor cells.

Lymphocyte counts declined the day after the first 3 doses and returned to baseline prior to subsequent doses.

Serum levels of cytokines (IFN-γ, TNFα, IL-2, IL-6, IL-10 and IL-1RA) and chemokines (CXCL9, CXCL10, CXCL11, hepatocyte growth factor, and monocyte chemoattractant protein-1) were increased during the first three doses of KIMMTRAK with peak levels between 8 to 24 hours after treatment with KIMMTRAK and levels returned to baseline prior to subsequent doses. In subsequent treatment cycles, cytokine elevation occurred in fewer patients with lesser intensity compared to the first 3 doses.

The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of KIMMTRAK have not been fully characterized.

After a single dose administration, tebentafusp-tebn Cmax and AUC0-7d increased in an approximately dose proportional manner from 20 to 68 mcg (0.3 to 1 times the approved recommended dose). Following administration of the approved recommended dosage in patients with metastatic uveal melanoma, the steady-state geometric mean (% CV) Cmax of tebentafusp-tebn is 13 ng/mL (34.6%) and AUC0-7d is 4.6 ng.day/mL (23%) with no accumulation.

Distribution

Tebentafusp-tebn geometric mean (% CV) steady-state volume of distribution is 7.56 L (24%).

Elimination

The geometric mean clearance of tebentafusp-tebn is 16.4 L/d (CV: 24.5%) and median terminal half-life is 7.5 hours (range: 6.8-7.5 hours).

Metabolism

Tebentafusp-tebn is expected to be catabolized into small peptides and amino acids.

Specific Populations

No clinically significant difference in the pharmacokinetics of tebentafusp-tebn were identified based on weight (43 to 163 kg), sex (48% female), age (23 to 91 years), or mild to moderate renal impairment based on creatinine clearance (CLcr) estimated by C-G formula (CLcr 30 to 89 mL/min) or mild hepatic impairment as measured by total bilirubin (TB) and aspartate aminotransferase (AST) (TB ≤ upper limit of normal (ULN) and AST > ULN or TB > 1 to 1.5x ULN and any AST).

Tebentafusp-tebn has not been studied in patients with severe (CLcr < 30 mL/min) renal impairment or in patients with moderate (TB >1.5 to 3x ULN, any AST) to severe (TB > 3 to 10x ULN, any AST) hepatic impairment.

Drug Interaction

Elevation of certain proinflammatory cytokines may suppress CYP450 enzyme activities.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other products or studies, including those of KIMMTRAK.

In studies IMCgp100-102 and IMCgp100-202, 36% (47/131) and 28% (67/240) of patients who were treated with tebentafusp-tebn at the recommended dosing regimen for up to 29 cycles and 45 cycles, respectively, developed anti-tebentafusp-tebn antibodies (ADA). Among the patients who developed ADAs, neutralizing antibodies (NAb) against tebentafusp-tebn were detected in 57% (27/47) and 63% (42/67), respectively, in studies IMCgp100-102 and IMCgp100-202. The median onset time to ADA formation was 8 and 12 weeks and 15 and 16 weeks for NAb formation after tebentafusp-tebn treatment in studies IMCgp100-102 and IMCgp100-202, respectively.

Tebentafusp-tebn exposure was lower in the presence of ADAs and NAbs. In Studies IMCgp100-102 and IMCgp100-202, tebentafusp-tebn treated patients who developed ADAs had tebentafusp-tebn concentrations (Cmax) that were 50% to 99% lower compared to patients who did not develop ADAs. Tebentafusp-tebn clearance was higher in patients with high titer ADAs (titers > 8192), resulting in a lower exposure (AUC0-7 days) by 97% compared to patients who did not develop ADA, and terminal half-life decreased to 10-14 minutes. Development of high titer Nabs (titers >100 in Study IMCgp100-102 or >640 in Study IMCgp100-202) resulted in lower Cmax of tebentafusp-tebn by 85% to 99% compared to patients who did not develop NAbs, and the tebentafusp-tebn concentrations (Cmax) became undetectable in 43.5% (30/69) of patients who developed NAbs in both studies.

The effect of ADA and NAb on pharmacodynamics, safety, or effectiveness of tebentafusp-tebn has not been fully characterized.

No carcinogenicity or genotoxicity studies have been conducted with tebentafusp-tebn.

No studies have been conducted to evaluate the effects of tebentafusp-tebn on fertility.

Study IMCgp100-202: First line metastatic uveal melanoma

{ "type": "p", "children": [], "text": "\nStudy IMCgp100-202: First line metastatic uveal melanoma\n" }

KIMMTRAK was evaluated in IMCgp100-202, a randomized, open-label, multicenter trial (NCT03070392) that enrolled patients with metastatic uveal melanoma (N=378). Patients were required to be HLA-A*02:01 genotype positive identified by a central assay. Patients were excluded if they received prior systemic therapy for metastatic or advanced uveal melanoma or localized liver-directed therapy. Prior surgical resection of oligometastatic disease was permitted. Patients with clinically significant cardiac disease or the presence of symptomatic or untreated brain metastasis were excluded.

{ "type": "p", "children": [], "text": "KIMMTRAK was evaluated in IMCgp100-202, a randomized, open-label, multicenter trial (NCT03070392) that enrolled patients with metastatic uveal melanoma (N=378). Patients were required to be HLA-A*02:01 genotype positive identified by a central assay. Patients were excluded if they received prior systemic therapy for metastatic or advanced uveal melanoma or localized liver-directed therapy. Prior surgical resection of oligometastatic disease was permitted. Patients with clinically significant cardiac disease or the presence of symptomatic or untreated brain metastasis were excluded." }

Patients were randomized (2:1) to receive KIMMTRAK weekly by intravenous infusion administered at 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (N=252) or Investigator’s choice (N=126) of pembrolizumab, ipilimumab, or dacarbazine. Randomization was stratified by lactate dehydrogenase (LDH) level at study entry. Across both arms, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity.

{ "type": "p", "children": [], "text": "Patients were randomized (2:1) to receive KIMMTRAK weekly by intravenous infusion administered at 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (N=252) or Investigator’s choice (N=126) of pembrolizumab, ipilimumab, or dacarbazine. Randomization was stratified by lactate dehydrogenase (LDH) level at study entry. Across both arms, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity." }

The major efficacy outcome was overall survival (OS). Additional efficacy outcomes were investigator-assessed progression free survival (PFS) and objective response rate (ORR) per RECIST 1.1.

{ "type": "p", "children": [], "text": "The major efficacy outcome was overall survival (OS). Additional efficacy outcomes were investigator-assessed progression free survival (PFS) and objective response rate (ORR) per RECIST 1.1." }

The median age was 64 years (range 23 to 92 years); 50% were female; 87% were White, and 12% were unreported or unknown race. The reported ethnicity was Hispanic or Latino in 2.4% of patients. Baseline ECOG performance status was 0 (73%), 1 (21%), or 2 (0.3%); 36% had elevated LDH level; and 94% had liver metastasis.

{ "type": "p", "children": [], "text": "The median age was 64 years (range 23 to 92 years); 50% were female; 87% were White, and 12% were unreported or unknown race. The reported ethnicity was Hispanic or Latino in 2.4% of patients. Baseline ECOG performance status was 0 (73%), 1 (21%), or 2 (0.3%); 36% had elevated LDH level; and 94% had liver metastasis." }

The efficacy results are summarized in Table 6 and Figure 1.

{ "type": "p", "children": [], "text": "The efficacy results are summarized in Table 6 and Figure 1." }

Table 6: Efficacy Results in Study IMCgp100-202

{ "type": "p", "children": [], "text": "\nTable 6: Efficacy Results in Study IMCgp100-202\n" }

<div class="scrollingtable"><table class="Noautorules" width="750"> <col align="center" width="34%"/> <col align="center" width="33%"/> <col align="center" width="33%"/> <tfoot> <tr> <td align="left" colspan="3">CI= Confidence Interval, HR= Hazard Ratio <br/> <span class="Sup">1</span> Based on prespecified interim analysis <br/> <span class="Sup">2</span> Hazard ratio is from a cox proportional hazards model stratified by LDH status <br/> <span class="Sup">3</span> Two-sided p-value based on log rank test stratified by LDH <br/> <span class="Sup">4</span> Compared to the interim efficacy boundary of 0.006 <br/> <span class="Sup">5</span> Final PFS analysis <br/> <span class="Sup">6</span> Compared to the efficacy boundary of 0.05. <br/> <span class="Sup">7</span> Not formally tested </td> </tr> </tfoot> <tbody class="Headless"> <tr valign="middle"> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"></span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">KIMMTRAK<br/>(N=252)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Investigator’s Choice (pembrolizumab, or ipilimumab, or dacarbazine)<br/>(N=126)</span></td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Overall Survival (OS)</span><span class="Sup">1</span></td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">Number of deaths</td><td align="center" class="Botrule Lrule Rrule">87 (34.5%)</td><td align="center" class="Botrule Lrule Rrule">63 (50%)</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">Median in months (95% CI)</td><td align="center" class="Botrule Lrule Rrule">21.7 (18.6, 28.6)</td><td align="center" class="Botrule Lrule Rrule">16 (9.7, 18.4)</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">HR (95% CI)<span class="Sup">2</span></td><td align="center" class="Botrule Lrule Rrule" colspan="2">0.51 (0.37, 0.71)</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">p-value<span class="Sup">3, 4</span></td><td align="center" class="Botrule Lrule Rrule" colspan="2">&lt;0.0001</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Progression-free Survival</span><span class="Sup">5</span></td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">Number (%) of patients with<br/> event</td><td align="center" class="Botrule Lrule Rrule">198 (78.6%)</td><td align="center" class="Botrule Lrule Rrule">97 (77%)</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">Median in months (95% CI)</td><td align="center" class="Botrule Lrule Rrule">3.3 (3, 5)</td><td align="center" class="Botrule Lrule Rrule">2.9 (2.8, 3)</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">HR (95% CI)<span class="Sup">2</span></td><td align="center" class="Botrule Lrule Rrule" colspan="2">0.73 (0.58, 0.94)</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">p-value<span class="Sup">3, 6</span></td><td align="center" class="Botrule Lrule Rrule" colspan="2">0.0139</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule"><span class="Bold">Objective Response Rate<br/> (95% CI)</span><span class="Sup">7</span></td><td align="center" class="Botrule Lrule Rrule">9.1% (5.9, 13.4)</td><td align="center" class="Botrule Lrule Rrule">4.8% (1.8, 10.1)</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">Complete Response</td><td align="center" class="Botrule Lrule Rrule">1 (0.4%)</td><td align="center" class="Botrule Lrule Rrule">0</td> </tr> <tr valign="middle"> <td align="left" class="Botrule Lrule Rrule">Partial Response</td><td align="center" class="Botrule Lrule Rrule">22 (8.7%)</td><td align="center" class="Botrule Lrule Rrule">6 (4.8%)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"750\">\n<col align=\"center\" width=\"34%\"/>\n<col align=\"center\" width=\"33%\"/>\n<col align=\"center\" width=\"33%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"3\">CI= Confidence Interval, HR= Hazard Ratio\n\t\t\t\t\t\t\t\t\t\t<br/>\n<span class=\"Sup\">1</span> Based on prespecified interim analysis\n\t\t\t\t\t\t\t\t\t\t<br/>\n<span class=\"Sup\">2</span> Hazard ratio is from a cox proportional hazards model stratified by LDH status\n\t\t\t\t\t\t\t\t\t\t<br/>\n<span class=\"Sup\">3</span> Two-sided p-value based on log rank test stratified by LDH\n\t\t\t\t\t\t\t\t\t\t<br/>\n<span class=\"Sup\">4</span> Compared to the interim efficacy boundary of 0.006\n\t\t\t\t\t\t\t\t\t\t<br/>\n<span class=\"Sup\">5</span> Final PFS analysis\n\t\t\t\t\t\t\t\t\t\t<br/>\n<span class=\"Sup\">6</span> Compared to the efficacy boundary of 0.05.\n\t\t\t\t\t\t\t\t\t\t<br/>\n<span class=\"Sup\">7</span> Not formally tested\n\t\t\t\t\t\t\t\t\t</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr valign=\"middle\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\"></span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">KIMMTRAK<br/>(N=252)</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Investigator’s Choice (pembrolizumab, or ipilimumab, or dacarbazine)<br/>(N=126)</span></td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Overall Survival (OS)</span><span class=\"Sup\">1</span></td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Number of deaths</td><td align=\"center\" class=\"Botrule Lrule Rrule\">87 (34.5%)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">63 (50%)</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Median in months (95% CI)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">21.7 (18.6, 28.6)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">16 (9.7, 18.4)</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">HR (95% CI)<span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\">0.51 (0.37, 0.71)</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">p-value<span class=\"Sup\">3, 4</span></td><td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\">&lt;0.0001</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Progression-free Survival</span><span class=\"Sup\">5</span></td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Number (%) of patients with<br/> event</td><td align=\"center\" class=\"Botrule Lrule Rrule\">198 (78.6%)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">97 (77%)</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Median in months (95% CI)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">3.3 (3, 5)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">2.9 (2.8, 3)</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">HR (95% CI)<span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\">0.73 (0.58, 0.94)</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">p-value<span class=\"Sup\">3, 6</span></td><td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\">0.0139</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\"><span class=\"Bold\">Objective Response Rate<br/> (95% CI)</span><span class=\"Sup\">7</span></td><td align=\"center\" class=\"Botrule Lrule Rrule\">9.1% (5.9, 13.4)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">4.8% (1.8, 10.1)</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Complete Response</td><td align=\"center\" class=\"Botrule Lrule Rrule\">1 (0.4%)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">0</td>\n</tr>\n<tr valign=\"middle\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\">Partial Response</td><td align=\"center\" class=\"Botrule Lrule Rrule\">22 (8.7%)</td><td align=\"center\" class=\"Botrule Lrule Rrule\">6 (4.8%)</td>\n</tr>\n</tbody>\n</table></div>" }

Figure 1: Kaplan-Meier Curves of Overall Survival in Study IMCgp100-202

{ "type": "p", "children": [], "text": "\nFigure 1: Kaplan-Meier Curves of Overall Survival in Study IMCgp100-202 \n" }

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

Each KIMMTRAK (tebentafusp-tebn) injection carton (NDC 80446-401-01) contains:

{ "type": "p", "children": [], "text": "Each KIMMTRAK (tebentafusp-tebn) injection carton (NDC 80446-401-01) contains:" }

{ "type": "ul", "children": [ "One single-dose vial containing 100 mcg of tebentafusp-tebn in 0.5 mL of sterile, preservative-free, clear, colorless or slightly yellowish solution." ], "text": "" }

The vial stopper is not made with natural rubber latex.

{ "type": "p", "children": [], "text": "The vial stopper is not made with natural rubber latex." }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

{ "type": "ul", "children": [ "Store KIMMTRAK vials in the original carton refrigerated at 2°C to 8°C (36°F to 46°F) and protect from light until time of use. Do not freeze. Do not shake." ], "text": "" }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information)." }

Cytokine Release Syndrome (CRS)

{ "type": "p", "children": [], "text": "\nCytokine Release Syndrome (CRS)\n" }

Inform patients of the risk of CRS, and to immediately contact their healthcare provider for signs and symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, nausea, vomiting, fatigue, or headache) [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Inform patients of the risk of CRS, and to immediately contact their healthcare provider for signs and symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, nausea, vomiting, fatigue, or headache) [see Warnings and Precautions (5.1)]." }

Skin Reactions

{ "type": "p", "children": [], "text": "\nSkin Reactions\n" }

Inform patients that rashes and skin reactions have occurred in patients who have received KIMMTRAK. Advise patients to contact their healthcare provider for signs and symptoms of progressive or intolerable skin reactions [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Inform patients that rashes and skin reactions have occurred in patients who have received KIMMTRAK. Advise patients to contact their healthcare provider for signs and symptoms of progressive or intolerable skin reactions [see Warnings and Precautions (5.2)]." }

Elevated Liver Enzymes

{ "type": "p", "children": [], "text": "\nElevated Liver Enzymes \n" }

Inform patients that elevations in liver enzymes have occurred in patients who have received KIMMTRAK. Advise patients to contact their healthcare provider for signs and symptoms of liver toxicity (e.g., right sided abdominal pain, jaundice, scleral icterus) [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients that elevations in liver enzymes have occurred in patients who have received KIMMTRAK. Advise patients to contact their healthcare provider for signs and symptoms of liver toxicity (e.g., right sided abdominal pain, jaundice, scleral icterus) [see Warnings and Precautions (5.3)]." }

Embryo-Fetal Toxicity

{ "type": "p", "children": [], "text": "\nEmbryo-Fetal Toxicity\n" }

{ "type": "ul", "children": [ "Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform females of the risk to a fetus [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)]. ", "Advise females of reproductive potential to use effective contraception while on KIMMTRAK and for 1 week after the last dose [see Use in Specific Populations (8.1) and (8.3)]. " ], "text": "" }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

{ "type": "ul", "children": [ "Advise patients not to breastfeed during treatment with KIMMTRAK and for 1 week after the last dose [see Use in Specific Populations (8.2)]." ], "text": "" }

Manufactured by: Immunocore Limited 92 Park Drive, Milton Park Abingdon, Oxfordshire United Kingdom, OX144RY License no: 2239

{ "type": "p", "children": [], "text": "\nManufactured by:\nImmunocore Limited\n\t\t\t\t\t\t\t92 Park Drive, Milton Park\n\t\t\t\t\t\t\tAbingdon, Oxfordshire\n\t\t\t\t\t\t\tUnited Kingdom, OX144RY\n\t\t\t\t\t\t\tLicense no: 2239" }

At: Baxter Oncology GmbH Kantstraβe 2 33790 Halle/Westfalen Germany

{ "type": "p", "children": [], "text": "\nAt:\nBaxter Oncology GmbH\n\t\t\t\t\t\t\tKantstraβe 2\n\t\t\t\t\t\t\t33790 Halle/Westfalen\n\t\t\t\t\t\t\tGermany" }

For: Immunocore Commercial LLC 181 Washington Street, Conshohocken, PA, US

{ "type": "p", "children": [], "text": "\nFor:\nImmunocore Commercial LLC\n\t\t\t\t\t\t\t181 Washington Street, \n\t\t\t\t\t\t\tConshohocken, PA, US" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" width="80%"/> <col align="left" width="20%"/> <tfoot> <tr> <td align="left">This Patient Information has been approved by the U.S. Food and Drug Administration       Issued: January 2022</td> </tr> </tfoot> <tbody class="Headless"> <tr valign="top"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">PATIENT INFORMATION</span> </p> <p> <span class="Bold">KIMMTRAK<span class="Sup">®</span>(KIM-track) <br/>(tebentafusp-tebn) <br/>Injection</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <a name="impinf"></a><span class="Bold">What is the most important information I should know about KIMMTRAK?</span> </p> <p> <span class="Bold">KIMMTRAK can cause serious side effects that can be severe or, life threatening, and usually happens within the first three infusions. These side effects include:</span> </p> <ul class="Disc"> <li> <span class="Bold">Cytokine Release Syndrome (CRS). Tell your healthcare provider right away if you get any of the following symptoms:</span> <ul> <li>fever</li> <li>tiredness or weakness</li> <li>vomiting</li> <li>chills</li> <li>nausea</li> <li>low blood pressure </li> <li>dizziness and light headedness</li> <li>headache</li> <li>wheezing and trouble breathing</li> <li>rash</li> </ul> </li> </ul> <p>Your healthcare provider will check for these problems during treatment with KIMMTRAK. Your healthcare provider may temporarily stop or completely stop your treatment with KIMMTRAK, if you have severe side effects.</p> <p> <span class="Bold">See “<a href="#psblsideeffects">What are the possible side effects of KIMMTRAK?</a></span>” for more information about side effects.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">What is KIMMTRAK?</span> </p> <br/> <p>KIMMTRAK is a prescription medicine used to treat HLA-A*02:01-positive adults with uveal melanoma that cannot be removed by surgery or has spread.</p> <br/> <p>Your healthcare provider will test you for a presence of HLA-A*02:01 gene to make sure KIMMTRAK is right for you. It is not known if KIMMTRAK is safe and effective in children.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Before you receive KIMMTRAK, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <ul class="Disc"> <li>are pregnant or plan to become pregnant. KIMMTRAK may harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with KIMMTRAK.</li> </ul> <p> <span class="Bold">For females who are able to become pregnant:</span> </p> <ul class="Disc"> <li>Your healthcare provider should do a pregnancy test before you start treatment with KIMMTRAK.</li> <li>Use an effective form of birth control during treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK.</li> <li>are breastfeeding or plan to breastfeed. It is not known if KIMMTRAK passes into your breast milk. Do not breastfeed during the treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK.</li> </ul> <p>Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">How will I receive KIMMTRAK?</span> </p> <ul class="Disc"> <li>KIMMTRAK will be given to you by intravenous (IV) infusion into your vein for 15 to 20 minutes.</li> <li>KIMMTRAK is usually given every week.</li> <li>Your healthcare provider will decide how many treatments you need.</li> <li>Your healthcare provider will keep you under observation for at least 16 hours following the first three KIMMTRAK treatments and for at least 30 minutes after future treatments.</li> <li>Your healthcare provider may delay your treatment of KIMMTRAK if you have certain side effects.</li> <li>Your healthcare provider may do blood tests regularly during treatment with KIMMTRAK.</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <a name="psblsideeffects"></a><span class="Bold">What are the possible side effects of KIMMTRAK?</span> </p> <p> <span class="Bold">KIMMTRAK can cause serious side effects, including:</span> </p> <ul class="Disc"> <li> <span class="Bold">See "<a href="#impinf">What is the most important information I should know about KIMMTRAK?</a>”.</span> </li> <li> <span class="Bold">Skin reactions</span>. KIMMTRAK may cause skin reactions that require treatment. Tell your healthcare provider if you get symptoms of skin reactions, such as rash, itching, or skin swelling, that are severe and do not go away.</li> <li> <span class="Bold">Abnormal liver blood tests. </span>Your healthcare provider will do blood tests to check your liver before you start KIMMTRAK and during treatment with KIMMTRAK. Tell your healthcare provider if you get symptoms of liver problems such as right-sided abdominal pain or yellowing of the skin or eyes.</li> </ul> <p> <span class="Bold">The most common side effects of KIMMTRAK include:</span> </p> <ul class="Disc"> <li>cytokine release syndrome (CRS)</li> <li>rash</li> <li>fever</li> <li>itching</li> <li>tiredness</li> <li>nausea</li> <li>chills</li> <li>stomach pain</li> <li>swelling</li> <li>low blood pressure (symptoms may include dizziness or light headedness)</li> <li>dry skin</li> <li>headache</li> <li>vomiting</li> <li>abnormal liver blood tests</li> </ul> <p>These are not all the possible side effects of KIMMTRAK.</p> <p>Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">General information about safe and effective use of KIMMTRAK.</span> </p> <br/> <p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. If you would like more information about KIMMTRAK, talk with your healthcare provider. You can ask your healthcare provider for more information about KIMMTRAK that is written for healthcare professionals.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">What are the ingredients in KIMMTRAK?</span> </p> <br/> <p> <span class="Bold">Active ingredient:</span> tebentafusp</p> <br/> <p> <span class="Bold">Inactive ingredients:</span> citric acid monohydrate, di-sodium hydrogen phosphate, mannitol, polysorbate 20, trehalose, and Water for injection.</p> <br/> <p> <span class="Bold">Manufactured by:</span> <br/>Immunocore Limited <br/>92 Park Drive, Milton Park <br/>Abingdon, Oxfordshire <br/>United Kingdom, OX144RY <br/>License no: 2239</p> <br/> <p>at: Baxter Oncology GmbH, Kantstraβe 2, 33790 Halle/Westfalen Germany.</p> <br/> <p>For: Immunocore Commercial LLC 181 Washington Street Conshohocken, PA, US</p> <br/> <p>KIMMTRAK is a trademark of the Immunocore Limited</p> <br/> <p>For more information, go to www.KIMMTRAK.com or call 1-844-IMMUNO1 (1-844-466-8661).</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" width=\"80%\"/>\n<col align=\"left\" width=\"20%\"/>\n<tfoot>\n<tr>\n<td align=\"left\">This Patient Information has been approved by the U.S. Food and Drug Administration       Issued: January 2022</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr valign=\"top\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">PATIENT INFORMATION</span>\n</p>\n<p>\n<span class=\"Bold\">KIMMTRAK<span class=\"Sup\">®</span>(KIM-track)\n\t\t\t\t\t\t\t\t\t\t\t<br/>(tebentafusp-tebn)\n\t\t\t\t\t\t\t\t\t\t\t<br/>Injection</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<a name=\"impinf\"></a><span class=\"Bold\">What is the most important information I should know about KIMMTRAK?</span>\n</p>\n<p>\n<span class=\"Bold\">KIMMTRAK can cause serious side effects that can be severe or, life threatening, and usually happens within the first three infusions. These side effects include:</span>\n</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Cytokine Release Syndrome (CRS). Tell your healthcare provider right away if you get any of the following symptoms:</span>\n<ul>\n<li>fever</li>\n<li>tiredness or weakness</li>\n<li>vomiting</li>\n<li>chills</li>\n<li>nausea</li>\n<li>low blood pressure </li>\n<li>dizziness and light headedness</li>\n<li>headache</li>\n<li>wheezing and trouble breathing</li>\n<li>rash</li>\n</ul>\n</li>\n</ul>\n<p>Your healthcare provider will check for these problems during treatment with KIMMTRAK. Your healthcare provider may temporarily stop or completely stop your treatment with KIMMTRAK, if you have severe side effects.</p>\n<p>\n<span class=\"Bold\">See “<a href=\"#psblsideeffects\">What are the possible side effects of KIMMTRAK?</a></span>” for more information about side effects.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What is KIMMTRAK?</span>\n</p>\n<br/>\n<p>KIMMTRAK is a prescription medicine used to treat HLA-A*02:01-positive adults with uveal melanoma that cannot be removed by surgery or has spread.</p>\n<br/>\n<p>Your healthcare provider will test you for a presence of HLA-A*02:01 gene to make sure KIMMTRAK is right for you. It is not known if KIMMTRAK is safe and effective in children.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Before you receive KIMMTRAK, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<ul class=\"Disc\">\n<li>are pregnant or plan to become pregnant. KIMMTRAK may harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with KIMMTRAK.</li>\n</ul>\n<p>\n<span class=\"Bold\">For females who are able to become pregnant:</span>\n</p>\n<ul class=\"Disc\">\n<li>Your healthcare provider should do a pregnancy test before you start treatment with KIMMTRAK.</li>\n<li>Use an effective form of birth control during treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if KIMMTRAK passes into your breast milk. Do not breastfeed during the treatment with KIMMTRAK and for at least 1 week after the last dose of KIMMTRAK.</li>\n</ul>\n<p>Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">How will I receive KIMMTRAK?</span>\n</p>\n<ul class=\"Disc\">\n<li>KIMMTRAK will be given to you by intravenous (IV) infusion into your vein for 15 to 20 minutes.</li>\n<li>KIMMTRAK is usually given every week.</li>\n<li>Your healthcare provider will decide how many treatments you need.</li>\n<li>Your healthcare provider will keep you under observation for at least 16 hours following the first three KIMMTRAK treatments and for at least 30 minutes after future treatments.</li>\n<li>Your healthcare provider may delay your treatment of KIMMTRAK if you have certain side effects.</li>\n<li>Your healthcare provider may do blood tests regularly during treatment with KIMMTRAK.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<a name=\"psblsideeffects\"></a><span class=\"Bold\">What are the possible side effects of KIMMTRAK?</span>\n</p>\n<p>\n<span class=\"Bold\">KIMMTRAK can cause serious side effects, including:</span>\n</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">See \"<a href=\"#impinf\">What is the most important information I should know about KIMMTRAK?</a>”.</span>\n</li>\n<li>\n<span class=\"Bold\">Skin reactions</span>. KIMMTRAK may cause skin reactions that require treatment. Tell your healthcare provider if you get symptoms of skin reactions, such as rash, itching, or skin swelling, that are severe and do not go away.</li>\n<li>\n<span class=\"Bold\">Abnormal liver blood tests. </span>Your healthcare provider will do blood tests to check your liver before you start KIMMTRAK and during treatment with KIMMTRAK. Tell your healthcare provider if you get symptoms of liver problems such as right-sided abdominal pain or yellowing of the skin or eyes.</li>\n</ul>\n<p>\n<span class=\"Bold\">The most common side effects of KIMMTRAK include:</span>\n</p>\n<ul class=\"Disc\">\n<li>cytokine release syndrome (CRS)</li>\n<li>rash</li>\n<li>fever</li>\n<li>itching</li>\n<li>tiredness</li>\n<li>nausea</li>\n<li>chills</li>\n<li>stomach pain</li>\n<li>swelling</li>\n<li>low blood pressure (symptoms may include dizziness or light headedness)</li>\n<li>dry skin</li>\n<li>headache</li>\n<li>vomiting</li>\n<li>abnormal liver blood tests</li>\n</ul>\n<p>These are not all the possible side effects of KIMMTRAK.</p>\n<p>Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">General information about safe and effective use of KIMMTRAK.</span>\n</p>\n<br/>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. If you would like more information about KIMMTRAK, talk with your healthcare provider. You can ask your healthcare provider for more information about KIMMTRAK that is written for healthcare professionals.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in KIMMTRAK?</span>\n</p>\n<br/>\n<p>\n<span class=\"Bold\">Active ingredient:</span> tebentafusp</p>\n<br/>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> citric acid monohydrate, di-sodium hydrogen phosphate, mannitol, polysorbate 20, trehalose, and Water for injection.</p>\n<br/>\n<p>\n<span class=\"Bold\">Manufactured by:</span>\n<br/>Immunocore Limited\n\t\t\t\t\t\t\t\t\t\t\t<br/>92 Park Drive, Milton Park\n\t\t\t\t\t\t\t\t\t\t\t<br/>Abingdon, Oxfordshire\n\t\t\t\t\t\t\t\t\t\t\t<br/>United Kingdom, OX144RY\n\t\t\t\t\t\t\t\t\t\t\t<br/>License no: 2239</p>\n<br/>\n<p>at: Baxter Oncology GmbH, Kantstraβe 2, 33790 Halle/Westfalen Germany.</p>\n<br/>\n<p>For: Immunocore Commercial LLC 181 Washington Street Conshohocken, PA, US</p>\n<br/>\n<p>KIMMTRAK is a trademark of the Immunocore Limited</p>\n<br/>\n<p>For more information, go to www.KIMMTRAK.com or call 1-844-IMMUNO1 (1-844-466-8661).</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }