TIVDAK

WARNING: OCULAR TOXICITY • TIVDAK can cause severe ocular toxicities resulting in changes in vision, including severe vision loss, and corneal ulceration. [see Warnings and Precautions (5.1) ]. • Conduct an ophthalmic exam, including an assessment of ocular symptoms, visual acuity, and slit lamp exam of the anterior segment of the eye prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . • Adhere to the required premedication and eye care before, during, and after infusion. [see Dosage and Administration (2.2) ]. • Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ]. WARNING: OCULAR TOXICITY See full prescribing information for complete boxed warning. • TIVDAK can cause severe ocular toxicities resulting in changes in vision, including severe vision loss and corneal ulceration. ( 5.1 ) • Conduct an ophthalmic exam, including an assessment of ocular symptoms, visual acuity, and slit lamp exam of the anterior segment of the eye prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. ( 2.2 , 5.1 ) • Adhere to the required premedication and eye care before, during, and after infusion. ( 2.2 ) • Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity. ( 2.3 , 5.1 )

5 WARNINGS AND PRECAUTIONS • Peripheral neuropathy: Monitor patients for new or worsening peripheral neuropathy. Withhold, reduce the dose, or permanently discontinue TIVDAK based on severity. ( 2.3 , 5.2 ) • Hemorrhage: Monitor patients for signs and symptoms of hemorrhage. Withhold, reduce the dose, or permanently discontinue TIVDAK based on severity. ( 2.3 , 5.3 ) • Pneumonitis: Severe, life-threatening, or fatal pneumonitis may occur. Withhold TIVDAK for persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK for Grade 3 or 4 pneumonitis. ( 2.3 , 5.4 ) • Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions, including events of fatal or life-threatening Stevens-Johnson syndrome (SJS), can occur in patients treated with TIVDAK. Immediately withhold TIVDAK for suspected severe cutaneous adverse reactions, including SJS. Permanently discontinue TIVDAK for confirmed Grade 3 or 4 severe cutaneous adverse reactions, including SJS. ( 2.3 , 5.5 ) • Embryo-fetal toxicity: TIVDAK can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Ocular Adverse Reactions TIVDAK can cause severe ocular adverse reactions, including conjunctivitis, keratopathy (keratitis, punctate keratitis, and ulcerative keratitis), and dry eye (increased lacrimation, eye pain, eye discharge, pruritus, irritation, and foreign body sensation), that may lead to changes in vision and/or corneal ulceration. Ocular adverse reactions occurred in 55% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common ocular adverse reactions were conjunctivitis (32%), dry eye (24%), keratopathy (17%), and blepharitis (5%). Grade 3 ocular adverse reactions occurred in 3.3% of patients, including severe ulcerative keratitis in 1.2% of patients. Nine patients (2.1%) experienced ulcerative keratitis (including one with perforation requiring corneal transplantation), six (1.4%) conjunctival ulcer, four (0.9%) corneal erosion, two (0.5%) conjunctival erosion, and two (0.5%) symblepharon. The median time to onset of the first ocular adverse reaction was 1.2 months (range, 0-17.1). Of the patients who experienced ocular events, 59% had complete resolution and 31% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of TIVDAK in 6% of patients with cervical cancer. In innovaTV 301, 8 (3.2%) patients experienced delayed ocular adverse reactions occurring more than 30 days after discontinuation of TIVDAK. These adverse reactions included 3 patients with ulcerative keratitis, and one patient (each) with keratitis, punctate keratitis and corneal erosion, blepharitis and conjunctival hyperemia, conjunctival scar, and conjunctivitis and xerophthalmia. Refer patients to an eye care provider to conduct an ophthalmic exam prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. The exam should include visual acuity, slit lamp exam of the anterior segment of the eye, and an assessment of normal eye movement and ocular signs or symptoms which include dry or irritated eyes, eye secretions or blurry vision. Adhere to the required premedication and eye care before, during, and after infusion to reduce the risk of ocular adverse reactions [see Dosage and Administration (2.2) ]. Monitor for ocular toxicity and promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold, reduce, or permanently discontinue TIVDAK based on the severity or persistence of the ocular adverse reaction [see Dosage and Administration (2.3) ]. 5.2 Peripheral Neuropathy Peripheral neuropathy occurred in 39% of patients with cervical cancer treated with TIVDAK across clinical trials; 6% of patients experienced Grade 3 peripheral neuropathy. Peripheral neuropathy adverse reactions included peripheral sensory neuropathy (23%), peripheral neuropathy (5%), paresthesia (3.8%), peripheral sensorimotor neuropathy (3.3%), muscular weakness (2.8%), and peripheral motor neuropathy (2.4%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain-Barre syndrome. The median time to onset of peripheral neuropathy was 2.4 months (range, 0-11.3). Of the patients who experienced peripheral neuropathy, 18% had complete resolution and 21% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Peripheral neuropathy led to discontinuation of TIVDAK in 7% of patients with cervical cancer. Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening peripheral neuropathy, withhold dose, then dose reduce, or permanently discontinue TIVDAK based on the severity of peripheral neuropathy [see Dosage and Administration (2.3) ] . 5.3 Hemorrhage Hemorrhage occurred in 51% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reaction was epistaxis (33%). Grade 3 hemorrhage occurred in 4% of patients. The median time to onset of hemorrhage was 0.3 months (range, 0-10.4). Of the patients who experienced hemorrhage, 71% had complete resolution and 12% had partial resolution (defined as a decrease in severity by one or more grades from the worst grade) at last follow-up. Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK [see Dosage and Administration (2.3) ] . 5.4 Pneumonitis Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody drug conjugates containing vedotin including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 4 patients (0.9%) experienced pneumonitis, including 1 patient who had a fatal outcome. Monitor patients for pulmonary symptoms indicative of pneumonitis. Symptoms may include hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis [see Dosage and Administration (2.3) ] . 5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including events of fatal or life-threatening SJS, can occur in patients treated with TIVDAK. Severe cutaneous adverse reactions occurred in 1.6% of patients with cervical cancer treated with TIVDAK across clinical trials. Grade ≥3 severe cutaneous adverse reactions occurred in 0.5% of patients, including 1 patient who had a fatal outcome. Monitor patients for signs or symptoms of severe cutaneous adverse reactions, which include target lesions, worsening skin reactions, blistering or peeling of the skin, painful sores in mouth, nose, throat, or genital area, fever or flu-like symptoms, and swollen lymph nodes. If signs or symptoms of severe cutaneous adverse reactions occur, withhold TIVDAK until the etiology of the reaction has been determined. Early consultation with a specialist is recommended to ensure greater diagnostic accuracy and appropriate management. Permanently discontinue TIVDAK for confirmed Grade 3 or 4 severe cutaneous adverse reactions, including SJS [see Dosage and Administration (2.3) ] . 5.6 Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, TIVDAK can cause fetal harm when administered to a pregnant woman. The small molecule component of TIVDAK, MMAE, administered to rats caused adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at exposures below those occurring clinically at the recommended dose. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose [see Use in Specific Populations (8.1 , 8.3 ), and Clinical Pharmacology (12.1) ].

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Ocular Adverse Reactions [see Boxed Warning , Warnings and Precautions (5.1) ] • Peripheral Neuropathy [see Warnings and Precautions (5.2) ] • Hemorrhage [see Warnings and Precautions (5.3) ] • Pneumonitis [see Warnings and Precautions (5.4) ] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased, peripheral neuropathy, conjunctival adverse reactions, nausea, fatigue, aspartate aminotransferase increased, epistaxis, alopecia, alanine aminotransferase increased, and hemorrhage. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Seagen Inc. at 1-855-4SEAGEN or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. The data in the WARNINGS AND PRECAUTIONS section reflect exposure to TIVDAK in 425 patients with recurrent or metastatic cervical cancer who received at least one dose of TIVDAK at 2 mg/kg intravenously every 3 weeks in innovaTV 301, innovaTV 204, innovaTV 201 (NCT02001623), innovaTV 202 (NCT02552121), innovaTV 203 (NCT03245736), and innovaTV 206 (NCT03913741). The median duration of treatment with TIVDAK was 3.7 months (range: 0.4-40.2). In this pooled safety population, the most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (45%), peripheral neuropathy (39%), conjunctival adverse reactions (38%), nausea (37%), fatigue (36%), aspartate aminotransferase increased (33%), epistaxis (33%), alopecia (31%), alanine aminotransferase increased (30%), and hemorrhage (28%). The data described in this section reflect exposure to TIVDAK from innovaTV 301 and innovaTV 204. innovaTV 301 The safety of TIVDAK was evaluated in an open-label, randomized study in patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy [see Clinical Studies (14.1) ]. A total of 250 patients received TIVDAK 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The median duration of treatment with TIVDAK was 3.7 months (range: 0.4-19). Serious adverse reactions occurred in 33% of patients receiving TIVDAK. The most common (≥2%) serious adverse reactions were urinary tract infection (4.8%), small intestinal obstruction (2.4%), sepsis (2%), abdominal pain (2%), and hemorrhage (2%). Fatal adverse reactions occurred in 1.6% of patients who received TIVDAK, including acute kidney injury (0.4%), pneumonia (0.4%), sepsis (0.4%) and Stevens-Johnson syndrome (0.4%). Adverse reactions leading to permanent discontinuation occurred in 15% of patients receiving TIVDAK; the most common (≥3%) adverse reactions leading to permanent discontinuation were peripheral neuropathy (6%) and ocular adverse reactions (6%). Adverse reactions leading to dose interruption occurred in 39% of patients receiving TIVDAK; the most common (≥3%) adverse reactions leading to dose interruption were ocular adverse reactions (16%) and peripheral neuropathy (6%). Adverse reactions leading to dose reduction occurred in 30% of patients receiving TIVDAK; the most common (≥3%) adverse reactions leading to dose reduction were peripheral neuropathy (10%) and ocular adverse reactions (10%). The ocular adverse reactions included conjunctival disorders (4.8%), keratopathy (4%), and dry eye (0.8%). The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving TIVDAK were hemoglobin decreased, peripheral neuropathy, conjunctival adverse reactions, aspartate aminotransferase increased, nausea, alanine aminotransferase increased, fatigue, sodium decreased, epistaxis, and constipation. Table 4 summarizes the all grade and Grade 3-4 adverse reactions from innovaTV 301. Table 4: Adverse Reactions (≥10%) in Patients Who Received TIVDAK in innovaTV 301 Adverse Reaction TIVDAK N=250 Chemotherapy N=239 All Grades Grade 3-4 All Grades Grade 3-4 % % % % Nervous system disorders Peripheral neuropathy Peripheral neuropathy includes peripheral sensory neuropathy, paresthesia, muscular weakness, peripheral sensorimotor neuropathy, peripheral motor neuropathy, neurotoxicity, gait disturbance, neuralgia, hypoaesthesia, neuropathy peripheral, and skin burning sensation 38 6 4.2 0.4 Eye disorders Conjunctival adverse reactions Conjunctival adverse reactions includes conjunctivitis, conjunctivitis bacterial, conjunctivitis viral, episcleritis, ocular hyperemia, conjunctival hemorrhage, conjunctival hyperemia, conjunctival ulcer, conjunctivitis allergic, conjunctival disorder, symblepharon, conjunctival erosion, conjunctival oedema, conjunctivochalasis, and conjunctival scar 37 0 1.7 0 Corneal adverse reactions Corneal adverse reactions includes keratitis, punctate keratitis, corneal erosion, ulcerative keratitis, corneal degeneration, corneal opacity, and keratopathy 21 3.2 0 0 Dry eye Dry eye includes dry eye, eye discharge, eye pruritus, eye pain, eye irritation, and lacrimation increased 21 0 1.7 0 Gastrointestinal disorders Nausea Nausea includes nausea and retching 33 0.4 40 2.1 Constipation 25 1.2 16 0 Diarrhea Diarrhea includes diarrhea and gastroenteritis 22 1.6 15 1.3 Abdominal Pain Abdominal pain includes abdominal pain, abdominal pain upper, abdominal discomfort, and abdominal pain lower 18 4 15 2.5 Vomiting 18 1.6 18 1.3 General Fatigue Fatigue includes fatigue and asthenia 28 6 32 6 Pyrexia 17 0.4 21 0.8 Pruritus 10 0.4 2.9 0 Vascular disorders Epistaxis 26 0 2.5 0 Hemorrhage Hemorrhage includes hematuria, vaginal hemorrhage, rectal hemorrhage, hemoptysis, anal hemorrhage, hemorrhage, gastrointestinal hemorrhage, hemorrhagic shock, lower gastrointestinal hemorrhage, gingival bleeding, tumor hemorrhage, intra-abdominal hemorrhage, gastric hemorrhage, genital hemorrhage, uterine hemorrhage, urinary tract hemorrhage, hemorrhoidal hemorrhage 21 2 11 2.5 Metabolism and nutrition disorders Decreased appetite 24 0.8 18 0.4 Decreased weight 10 0.4 5 0 Skin and subcutaneous tissue disorders Alopecia 24 0 2.9 0 Rash Rash includes rash maculo-papular, eczema, rash macular, rash pustular, dermatitis acneiform, erythema, rash, urticaria, dermatitis, and rash erythematous 17 1.6 16 1.3 Infections Urinary tract infection Urinary tract infection includes urinary tract infection, pyelonephritis acute, cystitis, and urinary tract infection bacterial 16 5 18 8 Clinically relevant adverse reactions in <10% of patients who received TIVDAK in innovaTV 301 include periorbital adverse reactions (9%) and intestinal obstruction (4.4%, including small bowel, large bowel, and malignant gastrointestinal obstruction). Table 5 summarizes the laboratory abnormalities in innovaTV 301. Table 5: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline In Patients Who Received TIVDAK in innovaTV 301 TIVDAK The denominator used to calculate the rate varied from 206 to 244 based on the number of patients with a baseline value and at least one post-treatment value. Chemotherapy All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3-4 (%) Hematology Hemoglobin decreased 41 7 70 23 Neutrophils decreased 16 3.3 39 17 Chemistry Aspartate aminotransferase increased 34 2.5 32 0.4 Alanine aminotransferase increased 30 3.3 35 2.6 Sodium decreased 27 0.4 27 0.4 Creatinine increased 23 2 26 2.2 Coagulation Activated partial thromboplastin time prolonged 16 1.9 17 0.5 innovaTV 204 The safety of TIVDAK was evaluated in a single arm study in patients (n=101) with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy [see Clinical Studies (14.1) ]. Patients received TIVDAK 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The median duration of treatment was 4.2 months (range: 0.7-16). Serious adverse reactions occurred in 43% of patients. The most common (≥3%) serious adverse reactions were ileus (6%), hemorrhage (5%), pneumonia (4%), peripheral neuropathy, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock (1%), pneumonitis (1%), sudden death (1%), and multisystem organ failure (1%). Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) adverse reactions leading to permanent discontinuation were peripheral neuropathy (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most (≥3%) common adverse reactions leading to dose interruption were peripheral neuropathy (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) adverse reactions leading to dose reduction were conjunctival adverse reactions (9%) and corneal adverse reactions (8%). The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased, fatigue, lymphocytes decreased, nausea, peripheral neuropathy, alopecia, epistaxis, conjunctival adverse reactions, hemorrhage, leukocytes decreased, creatinine increased, dry eye, prothrombin international normalized ratio increased, activated partial thromboplastin time prolonged, diarrhea, and rash. Table 6 summarizes the all grade and Grade 3-4 adverse reactions from innovaTV 204. Table 6: Adverse Reactions (≥10%) in Patients Who Received TIVDAK in innovaTV 204 Adverse Reaction TIVDAK N=101 All Grades % Grade 3-4 % General Fatigue Fatigue includes fatigue and asthenia 50 7 Pyrexia 16 1 Pruritus 13 1 Gastrointestinal disorders Nausea Nausea includes nausea and retching 41 0 Diarrhea Diarrhea includes diarrhea, gastroenteritis, and colitis 25 2 Constipation 23 2 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal distention and abdominal discomfort 23 1 Vomiting 17 2 Nervous system disorders Peripheral neuropathy Peripheral neuropathy includes neuropathy peripheral, peripheral sensorimotor neuropathy, polyneuropathy, peripheral sensory neuropathy, paresthesia, hypoesthesia, burning sensation, neuralgia, sensory loss, peripheral motor neuropathy, muscular weakness, gait disturbance, and hyperesthesia 39 7 Skin and subcutaneous tissue disorders Alopecia 39 0 Rash Rash includes rash, rash maculo-papular, rash macular, dermatitis acneiform, dermatitis allergic, and erythema 25 0 Vascular disorders Epistaxis 39 0 Hemorrhage Hemorrhage includes vaginal hemorrhage, hematuria, rectal hemorrhage, cystitis hemorrhagic, lower gastrointestinal hemorrhage, urinary bladder hemorrhage, hematochezia, anal hemorrhage, gingival bleeding, post procedural hemorrhage, radiation associated with hemorrhage, metrorrhagia, large intestinal hemorrhage, paranasal sinus hemorrhage, and hemoptysis 32 6 Eye disorders Conjunctival adverse reactions Conjunctival adverse reactions includes conjunctivitis, conjunctival abrasion, conjunctival erosion, conjunctival hyperemia, conjunctival scar, noninfective conjunctivitis, ocular hyperemia, and conjunctival hemorrhage 37 0 Dry eye Dry eye includes dry eye and lacrimation increased 29 0 Corneal adverse reactions Corneal adverse reactions includes keratitis, punctate keratitis, ulcerative keratitis, corneal erosion, corneal scar, keratopathy, and corneal bleeding 21 3 Periorbital adverse reactions Periorbital adverse reactions includes blepharitis, meibomianitis, eye pruritus, entropion, trichiasis, chalazion, and meibomian gland dysfunction 16 0 Musculoskeletal and connective tissue disorders Myalgia Myalgia includes myalgia, musculoskeletal discomfort, and musculoskeletal pain 21 0 Arthralgia 16 0 Pain in extremity Pain in extremity includes pain in extremity and limb discomfort 13 1 Metabolism and nutrition disorders Decreased appetite 16 1 Infections Urinary tract infection Urinary tract infection includes urinary tract infection, urinary tract infection bacterial, and cystitis 14 2 Investigations Weight decreased 12 0 Clinically relevant adverse reactions in <10% of patients who received TIVDAK in innovaTV 204 included venous thrombosis (3%), pulmonary embolism (3%), and pneumonitis (2%). Table 7 summarizes the laboratory abnormalities in innovaTV 204. Table 7: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline In Patients Who Received TIVDAK in innovaTV 204 Laboratory Abnormality TIVDAK The denominator used to calculate the rate varied from 96 to 101 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Hemoglobin decreased 52 7 Neutrophils decreased 21 3 Chemistry Creatinine increased 29 4.1 Alanine aminotransferase increased 24 0 Aspartate aminotransferase increased 18 0 Sodium decreased 20 0 Alkaline phosphatase increased 17 0 Creatinine kinase increased 16 2.1 Magnesium decreased 17 2.1 Coagulation Prothrombin international normalized ratio increased 26 0 Activated partial thromboplastin time prolonged 26 2

<table ID="reftable4" styleCode="Noautorules" width="100%"><caption>Table 4: Adverse Reactions (&#x2265;10%) in Patients Who Received TIVDAK in innovaTV 301</caption><col width="24%"/><col width="19%"/><col width="19%"/><col width="19%"/><col width="19%"/><tbody><tr><td align="center" rowspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">TIVDAK</content> <content styleCode="bold">N=250</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Chemotherapy</content> <content styleCode="bold">N=239</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade 3-4</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade 3-4</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Peripheral neuropathy<footnote ID="_RefSPLSERV-8024FFEE-14CF-7BC2-BF5D-96B8">Peripheral neuropathy includes peripheral sensory neuropathy, paresthesia, muscular weakness, peripheral sensorimotor neuropathy, peripheral motor neuropathy, neurotoxicity, gait disturbance, neuralgia, hypoaesthesia, neuropathy peripheral, and skin burning sensation</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>38</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Eye disorders </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Conjunctival adverse reactions<footnote ID="_RefSPLSERV-A82AE759-F452-4D0D-18C6-8345">Conjunctival adverse reactions includes conjunctivitis, conjunctivitis bacterial, conjunctivitis viral, episcleritis, ocular hyperemia, conjunctival hemorrhage, conjunctival hyperemia, conjunctival ulcer, conjunctivitis allergic, conjunctival disorder, symblepharon, conjunctival erosion, conjunctival oedema, conjunctivochalasis, and conjunctival scar</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>37</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Corneal adverse reactions<footnote ID="_RefSPLSERV-23B48137-1D08-4F92-2DB1-7D4F">Corneal adverse reactions includes keratitis, punctate keratitis, corneal erosion, ulcerative keratitis, corneal degeneration, corneal opacity, and keratopathy</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dry eye<footnote ID="_RefSPLSERV-073D1FD2-3646-6256-A123-5806">Dry eye includes dry eye, eye discharge, eye pruritus, eye pain, eye irritation, and lacrimation increased</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea<footnote ID="_RefSPLSERV-3E3DC1E3-BC50-F463-7E0B-645C">Nausea includes nausea and retching</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>33</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>40</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea<footnote ID="_RefSPLSERV-AA93F841-3105-6C63-58A1-D9E4">Diarrhea includes diarrhea and gastroenteritis</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Abdominal Pain<footnote ID="_RefSPLSERV-DF8B51BE-3EDD-EAC2-39C6-298E">Abdominal pain includes abdominal pain, abdominal pain upper, abdominal discomfort, and abdominal pain lower</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vomiting </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.3</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue<footnote ID="_RefSPLSERV-612B5585-E6B2-332E-2032-76EC">Fatigue includes fatigue and asthenia</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>32</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pyrexia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pruritus</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Vascular disorders </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Epistaxis </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>26</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hemorrhage<footnote ID="_RefSPLSERV-6FEA930E-C0E8-B2C3-5BDA-0A4F">Hemorrhage includes hematuria, vaginal hemorrhage, rectal hemorrhage, hemoptysis, anal hemorrhage, hemorrhage, gastrointestinal hemorrhage, hemorrhagic shock, lower gastrointestinal hemorrhage, gingival bleeding, tumor hemorrhage, intra-abdominal hemorrhage, gastric hemorrhage, genital hemorrhage, uterine hemorrhage, urinary tract hemorrhage, hemorrhoidal hemorrhage</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased appetite </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased weight</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and subcutaneous tissue disorders </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Alopecia </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Rash<footnote ID="_RefSPLSERV-9575BB74-FC4D-34F5-B716-0FAB">Rash includes rash maculo-papular, eczema, rash macular, rash pustular, dermatitis acneiform, erythema, rash, urticaria, dermatitis, and rash erythematous</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.3</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Infections</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Urinary tract infection<footnote ID="_RefSPLSERV-9BCEB3BC-7A79-7725-C9C0-5495">Urinary tract infection includes urinary tract infection, pyelonephritis acute, cystitis, and urinary tract infection bacterial</footnote></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>8</paragraph></td></tr></tbody></table>

<table ID="reftable5" styleCode="Noautorules" width="100%"><caption>Table 5: Select Laboratory Abnormalities (&#x2265;10%) That Worsened from Baseline In Patients Who Received TIVDAK in innovaTV 301</caption><col width="20%"/><col width="20%"/><col width="20%"/><col width="20%"/><col width="20%"/><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"/><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">TIVDAK</content><footnote ID="_RefSPLSERV-1C773E9B-3533-6C94-4B16-6C62">The denominator used to calculate the rate varied from 206 to 244 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Chemotherapy</content><footnoteRef IDREF="_RefSPLSERV-1C773E9B-3533-6C94-4B16-6C62"/></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades</content> <content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grades 3 or 4</content> <content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades</content> <content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grades 3-4</content> <content styleCode="bold">(%)</content></paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Hematology</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hemoglobin decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>41</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>70</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>23</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Neutrophils decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>39</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Chemistry</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Aspartate aminotransferase increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>34</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>32</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Alanine aminotransferase increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>30</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>35</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sodium decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>27</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>27</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Creatinine increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>26</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.2</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Coagulation</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Activated partial thromboplastin time prolonged</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>1.9</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.5</paragraph></td></tr></tbody></table>

<table ID="reftable6" styleCode="Noautorules" width="100%"><caption>Table 6: Adverse Reactions (&#x2265;10%) in Patients Who Received TIVDAK in innovaTV 204 </caption><col width="34%"/><col width="34%"/><col width="33%"/><tbody><tr><td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">TIVDAK</content> <content styleCode="bold">N=101</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades %</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade 3-4 %</content></paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue<footnote ID="_RefSPLSERV-15032FA1-7AAD-3F16-4D88-B9E0">Fatigue includes fatigue and asthenia</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>50</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pyrexia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pruritus</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea<footnote ID="_RefSPLSERV-3A6E047D-3A01-F46F-904C-79BB">Nausea includes nausea and retching</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>41</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea<footnote ID="_RefSPLSERV-AC4E1FAE-EE58-E235-7672-DE67">Diarrhea includes diarrhea, gastroenteritis, and colitis</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Abdominal pain<footnote ID="_RefSPLSERV-5712919E-2987-9FA9-04F6-5C24">Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal distention and abdominal discomfort</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vomiting </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Peripheral neuropathy<footnote ID="_RefSPLSERV-644F9784-7980-C0A8-818E-4B3D">Peripheral neuropathy includes neuropathy peripheral, peripheral sensorimotor neuropathy, polyneuropathy, peripheral sensory neuropathy, paresthesia, hypoesthesia, burning sensation, neuralgia, sensory loss, peripheral motor neuropathy, muscular weakness, gait disturbance, and hyperesthesia</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>39</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Alopecia </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>39</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Rash<footnote ID="_RefSPLSERV-058A414C-ED03-09D3-FFB4-1534">Rash includes rash, rash maculo-papular, rash macular, dermatitis acneiform, dermatitis allergic, and erythema</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Vascular disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Epistaxis</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>39</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hemorrhage<footnote ID="_RefSPLSERV-00CF1759-C51F-DB41-0629-330D">Hemorrhage includes vaginal hemorrhage, hematuria, rectal hemorrhage, cystitis hemorrhagic, lower gastrointestinal hemorrhage, urinary bladder hemorrhage, hematochezia, anal hemorrhage, gingival bleeding, post procedural hemorrhage, radiation associated with hemorrhage, metrorrhagia, large intestinal hemorrhage, paranasal sinus hemorrhage, and hemoptysis</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>32</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Eye disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Conjunctival adverse reactions<footnote ID="_RefSPLSERV-771832D7-8D85-E48C-AD17-892F">Conjunctival adverse reactions includes conjunctivitis, conjunctival abrasion, conjunctival erosion, conjunctival hyperemia, conjunctival scar, noninfective conjunctivitis, ocular hyperemia, and conjunctival hemorrhage</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>37</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dry eye<footnote ID="_RefSPLSERV-31903012-B3C1-659E-E1C9-D2DB">Dry eye includes dry eye and lacrimation increased</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>29</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Corneal adverse reactions<footnote ID="_RefSPLSERV-E77F164D-EB94-5B14-C1F3-2C7C">Corneal adverse reactions includes keratitis, punctate keratitis, ulcerative keratitis, corneal erosion, corneal scar, keratopathy, and corneal bleeding</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Periorbital adverse reactions<footnote ID="_RefSPLSERV-7EA1E8D9-6361-50AF-8F40-5B09">Periorbital adverse reactions includes blepharitis, meibomianitis, eye pruritus, entropion, trichiasis, chalazion, and meibomian gland dysfunction</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Myalgia<footnote ID="_RefSPLSERV-C6B9404F-ABCB-F1C3-3BB4-A677">Myalgia includes myalgia, musculoskeletal discomfort, and musculoskeletal pain</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Arthralgia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pain in extremity<footnote ID="_RefSPLSERV-2C7530A8-56C8-3B1F-398E-5336">Pain in extremity includes pain in extremity and limb discomfort</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Infections</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Urinary tract infection<footnote ID="_RefSPLSERV-2DF8E0DC-8369-7EBC-19B0-7698">Urinary tract infection includes urinary tract infection, urinary tract infection bacterial, and cystitis</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Investigations</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Weight decreased</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td></tr></tbody></table>