<?xml version="1.0" encoding="UTF-8"?><section ID="S6">
<id root="fad178d1-8af0-4134-b20f-536fa31ab038"/>
<code code="34084-4" codeSystem="2.16.840.1.113883.6.1" displayName="ADVERSE REACTIONS SECTION"/>
<title>6 ADVERSE REACTIONS</title>
<text>
<paragraph>The following clinically significant adverse reactions are described elsewhere in the labeling:</paragraph>
<list listType="unordered" styleCode="disc">
<item>Interstitial Lung Disease/Pneumonitis <content styleCode="italics">[see <linkHtml href="#S5.1">Warnings and Precautions (5.1)</linkHtml>]</content>
</item>
<item>Ocular Adverse Reactions <content styleCode="italics">[see <linkHtml href="#S5.2">Warnings and Precautions (5.2)</linkHtml>]</content>
</item>
<item>Stomatitis <content styleCode="italics">[see <linkHtml href="#S5.3">Warnings and Precautions (5.3)</linkHtml>]</content>
</item>
</list>
</text>
<effectiveTime value="20260527"/>
<excerpt>
<highlight>
<text>
<paragraph>The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with:</paragraph>
<list listType="unordered" styleCode="disc">
<item>
<content styleCode="underline">EGFR-mutated NSCLC</content> were stomatitis, nausea, alopecia, fatigue, decreased hemoglobin, decreased lymphocytes, constipation, increased calcium, increased AST, decreased white blood cell count, increased lactate dehydrogenase, musculoskeletal pain, decreased appetite, increased ALT, and rash. (<linkHtml href="#S6.1">6.1</linkHtml>)</item>
<item>
<content styleCode="underline">TNBC</content> were stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium, decreased lymphocytes, fatigue, decreased neutrophils, increased ALT, increased AST, dry eye, keratitis, decreased albumin, vomiting, musculoskeletal pain, decreased sodium, and increased blood alkaline phosphatase. (<linkHtml href="#S6.1">6.1</linkHtml>)</item>
<item>
<content styleCode="underline">HR-positive, HER2-negative breast cancer</content> were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase. (<linkHtml href="#S6.1">6.1</linkHtml>)</item>
</list>
<br/>
<paragraph styleCode="bold">To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.</paragraph>
</text>
</highlight>
</excerpt>
<component>
<section ID="S6.1">
<id root="651f3827-77b6-4587-8c9a-dfef4f7f219c"/>
<code code="90374-0" codeSystem="2.16.840.1.113883.6.1" displayName="CLINICAL TRIALS EXPERIENCE SECTION"/>
<title>6.1 Clinical Trials Experience</title>
<text>
<paragraph>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.</paragraph>
<paragraph>The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY in 1365 patients as a single agent at 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. This included 137 patients with NSCLC in TROPION-Lung05 <content styleCode="italics">[see <linkHtml href="#S14.1">Clinical Studies (14.1)</linkHtml>]</content>, 297 patients with NSCLC in TROPION-Lung01 <content styleCode="italics">[see <linkHtml href="#S14.1">Clinical Studies (14.1)</linkHtml>]</content>, 360 patients with HR-positive, HER2-negative breast cancer in TROPION-Breast01 <content styleCode="italics">[see <linkHtml href="#S14.3">Clinical Studies (14.3)</linkHtml>]</content>, 319 patients with TNBC in TROPION-Breast02 <content styleCode="italics">[see <linkHtml href="#S14.2">Clinical Studies (14.2)</linkHtml>]</content>, 50 patients with NSCLC and 83 patients with breast cancer in TROPION-PanTumor01 (NCT03401385), and 40 patients with NSCLC and 79 patients with breast cancer in TROPION-PanTumor02 (NCT05460273). Among the 1365 patients who received DATROWAY, 48% were exposed for greater than 6 months and 22% were exposed for greater than one year. In this pooled safety population, the most common (≥20%) adverse reactions were stomatitis (63%), nausea (51%), fatigue (42%), alopecia (38%), constipation (30%), vomiting (23%), decreased appetite (22%), and rash (20%). In this pooled safety population, the most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (8%), decreased hemoglobin (3.7%), decreased sodium (3.0%), and decreased blood potassium (2.3%). </paragraph>
<paragraph styleCode="underline">Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer </paragraph>
<paragraph styleCode="italics">TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 </paragraph>
<paragraph>The safety of DATROWAY was evaluated in 125 patients with EGFR-mutated NSCLC who received DATROWAY 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity in TROPION-Lung05 and TROPION-Lung01 <content styleCode="italics">[see <linkHtml href="#S14.1">Clinical Studies (14.1)</linkHtml>]</content> as well as TROPION-PanTumor01 (NCT03401385). Among these patients, the median duration of treatment was 6.1 months (range 0.7 months to 41.7 months).</paragraph>
<paragraph>The median age was 63 years (range: 36 to 81), 56% of patients were <65 years, 62% of patients were female; 66% were Asian, 26% were White, 0.8% were Black, 6% were other races; and 2.4% were of Hispanic ethnicity.</paragraph>
<paragraph>Serious adverse reactions occurred in 26% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were COVID-19 (4%), stomatitis (2.4%), and pneumonia (1.6%). Fatal adverse reactions occurred in 1.6% of patients who received DATROWAY, due to death not otherwise specified.</paragraph>
<paragraph>Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >1% of patients included ILD/pneumonitis (2.4%) and abnormal hepatic function (1.6%). </paragraph>
<paragraph>Dosage interruptions of DATROWAY due to an adverse reaction occurred in 43% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (13%), stomatitis (7%), fatigue (6%), pneumonia (4%), anemia (2.4%), amylase increased (2.4%), keratitis (2.4%), ILD/pneumonitis (1.6%), decreased appetite (1.6%), dyspnea (1.6%), rash (1.6%), and infusion-related reaction (1.6%). </paragraph>
<paragraph>Dose reductions of DATROWAY due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (14%), keratitis (1.6%), fatigue (1.6%), decreased weight (1.6%) and COVID-19 (1.6%).</paragraph>
<paragraph>The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis, nausea, alopecia, fatigue, decreased hemoglobin, decreased lymphocytes, constipation, increased calcium, increased AST, decreased white blood cell count, increased lactate dehydrogenase, musculoskeletal pain, decreased appetite, increased ALT, and rash. </paragraph>
<table width="90%">
<caption>Table 4: Adverse Reactions (≥10%) in Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC Who Received DATROWAY in TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01</caption>
<col align="left" valign="middle" width="50%"/>
<col align="center" valign="middle" width="25%"/>
<col align="center" valign="middle" width="25%"/>
<thead>
<tr>
<th align="center" rowspan="2" styleCode="Lrule Rrule">Adverse Reaction</th>
<th colspan="2" styleCode="Botrule Rrule">DATROWAY<br/>N=125</th>
</tr>
<tr>
<th align="center" styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4<br/>%</th>
</tr>
</thead>
<tfoot>
<tr>
<td align="left" colspan="3" valign="top">Events were graded using NCI CTCAE v5.0.</td>
</tr>
</tfoot>
<tbody>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Gastrointestinal disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Stomatitis<footnote ID="Tb4fta">Includes other related terms</footnote>
</td>
<td styleCode="Rrule">71</td>
<td styleCode="Rrule">9</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Nausea</td>
<td styleCode="Rrule">50</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Constipation</td>
<td styleCode="Rrule">31</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Vomiting</td>
<td styleCode="Rrule">16</td>
<td styleCode="Rrule">0.8</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Diarrhea</td>
<td styleCode="Rrule">12</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule">
<content styleCode="bold">Skin and subcutaneous tissue disorders</content>
</td>
<td styleCode="Rrule"/>
<td styleCode="Rrule"/>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Alopecia</td>
<td styleCode="Rrule">49</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Rash<footnoteRef IDREF="Tb4fta"/>
</td>
<td styleCode="Rrule">20</td>
<td styleCode="Rrule">0.8</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Pruritus</td>
<td styleCode="Rrule">12</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">General disorders and administration site conditions</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Fatigue<footnote>Includes fatigue, asthenia, and malaise</footnote>
</td>
<td styleCode="Rrule">42</td>
<td styleCode="Rrule">6</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Musculoskeletal and connective tissue disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Musculoskeletal pain</td>
<td styleCode="Rrule">22</td>
<td styleCode="Rrule">0.8</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Metabolism and nutrition disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased appetite</td>
<td styleCode="Rrule">20</td>
<td styleCode="Rrule">1.6</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Infections and Infestations</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> COVID-19<footnoteRef IDREF="Tb4fta"/>
</td>
<td styleCode="Rrule">19</td>
<td styleCode="Rrule">2.4</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Cough<footnoteRef IDREF="Tb4fta"/>
</td>
<td styleCode="Rrule">18</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Dyspnea</td>
<td styleCode="Rrule">11</td>
<td styleCode="Rrule">2.4</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Eye disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Dry eye</td>
<td styleCode="Rrule">13</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Keratitis<footnote>Includes corneal disorder, corneal erosion, keratitis, punctate keratitis, and ulcerative keratitis</footnote>
</td>
<td styleCode="Rrule">12</td>
<td styleCode="Rrule">2.4</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Injury, poisoning and procedural complications</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Infusion-related reaction<footnoteRef IDREF="Tb4fta"/>
</td>
<td styleCode="Rrule">13</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Nervous system disorders</content>
</td>
</tr>
<tr>
<td styleCode="Lrule Rrule"> Headache</td>
<td styleCode="Rrule">13</td>
<td styleCode="Rrule">0</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included dry skin, blurred vision, abdominal pain, conjunctivitis, dry mouth, ILD/pneumonitis, skin hyperpigmentation, increased lacrimation, and visual impairment. </paragraph>
<table width="90%">
<caption>Table 5: Select Laboratory Abnormalities (≥20%) that Worsened from Baseline in Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC Who Received DATROWAY in TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01</caption>
<col align="left" valign="top" width="50%"/>
<col align="center" valign="top" width="25%"/>
<col align="center" valign="top" width="25%"/>
<thead>
<tr>
<th align="center" rowspan="2" styleCode="Lrule Rrule" valign="middle">Laboratory Abnormality<footnote>Frequencies were based on NCI CTCAE v5.0 grade-derived laboratory abnormalities.</footnote>
</th>
<th colspan="2" styleCode="Botrule Rrule">DATROWAY<footnote>The denominator used to calculate the rate varied from 115 to 124 based on the number of patients with a baseline value and at least one post-treatment value.</footnote>
</th>
</tr>
<tr>
<th align="center" styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4<br/>%</th>
</tr>
</thead>
<tbody>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Hematology</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule">Decreased hemoglobin</td>
<td styleCode="Rrule">34</td>
<td styleCode="Rrule">4.8</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule">Decreased lymphocytes</td>
<td styleCode="Rrule">32</td>
<td styleCode="Rrule">11</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule">Decreased white blood cell count</td>
<td styleCode="Rrule">27</td>
<td styleCode="Rrule">1.6</td>
</tr>
<tr styleCode="Botrule">
<td colspan="3" styleCode="Lrule Rrule">
<content styleCode="bold">Chemistry</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule">Increased calcium</td>
<td styleCode="Rrule">31</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule">Increased AST</td>
<td styleCode="Rrule">28</td>
<td styleCode="Rrule">2.4</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule">Increased lactate dehydrogenase</td>
<td styleCode="Rrule">23</td>
<td styleCode="Rrule">0</td>
</tr>
<tr>
<td styleCode="Lrule Rrule">Increased ALT</td>
<td styleCode="Rrule">20</td>
<td styleCode="Rrule">2.4</td>
</tr>
</tbody>
</table>
<paragraph styleCode="underline">Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC) </paragraph>
<paragraph styleCode="italics">TROPION-Breast02 </paragraph>
<paragraph>The safety of DATROWAY was evaluated in 319 patients with triple-negative breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast02 <content styleCode="italics">[see <linkHtml href="#S14.2">Clinical Studies (14.2)</linkHtml>].</content> DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 8.5 months (range: 0.7 months to 38.0 months) for patients who received DATROWAY.</paragraph>
<paragraph>Serious adverse reactions occurred in 17% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were pneumonia (2.2%), vomiting (1.9%), COVID-19 (1.6%), and anemia (1.3%). Fatal adverse reactions occurred in one patient (0.3%) who received DATROWAY and was due to ILD/pneumonitis.</paragraph>
<paragraph>Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 4.7% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (0.9%) and keratitis (0.9%).</paragraph>
<paragraph>Dosage interruptions of DATROWAY due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption in >1% of patients included stomatitis (5%), increased amylase (4.1%), keratitis (3.4%), neutropenia (3.1%), COVID-19 (2.8%), pneumonia (2.2%), dry eye (1.9%), upper respiratory tract infection (1.6%), anemia (1.3%), leukopenia (1.3%), IRR (1.3%), and ILD/pneumonitis (1.3%).</paragraph>
<paragraph>Dose reductions of DATROWAY due to an adverse reaction occurred in 28% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (11%), keratitis (4.1%), fatigue (3.8%), increased amylase (2.8%), and pneumonia (1.3%).</paragraph>
<paragraph>The most common (≥20%) adverse reactions, including laboratory abnormalities in patients receiving DATROWAY, were stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium, decreased lymphocytes, fatigue, decreased neutrophils, increased ALT, increased AST, dry eye, keratitis, decreased albumin, vomiting, musculoskeletal pain, decreased sodium, and increased blood alkaline phosphatase. </paragraph>
<table ID="Table6" width="90%">
<caption>Table 6: Adverse Reactions (≥10%) in Patients Who Received DATROWAY in TROPION-Breast02</caption>
<col align="left" valign="middle" width="32%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<thead>
<tr styleCode="Botrule">
<th align="center" rowspan="2" styleCode="Lrule Rrule">Adverse Reactions</th>
<th colspan="2" styleCode="Rrule">DATROWAY<br/>N=319</th>
<th colspan="2" styleCode="Rrule">Chemotherapy<br/>N=309</th>
</tr>
<tr>
<th align="center" styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4<br/>%</th>
<th styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4<br/>%</th>
</tr>
</thead>
<tfoot>
<tr>
<td align="left" colspan="5" valign="top">Events were graded using NCI CTCAE v5.0.</td>
</tr>
</tfoot>
<tbody>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Gastrointestinal Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Stomatitis <footnote ID="t4fa">Includes other related terms </footnote>
</td>
<td styleCode="Rrule">63</td>
<td styleCode="Rrule">8</td>
<td styleCode="Rrule">14</td>
<td styleCode="Rrule">0.3</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Nausea</td>
<td styleCode="Rrule">48</td>
<td styleCode="Rrule">0.6</td>
<td styleCode="Rrule">22</td>
<td styleCode="Rrule">0.6</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Constipation</td>
<td styleCode="Rrule">40</td>
<td styleCode="Rrule">0.3</td>
<td styleCode="Rrule">17</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Vomiting</td>
<td styleCode="Rrule">23</td>
<td styleCode="Rrule">1.6</td>
<td styleCode="Rrule">11</td>
<td styleCode="Rrule">0.6</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Alopecia</td>
<td styleCode="Rrule">43</td>
<td styleCode="Rrule">0</td>
<td styleCode="Rrule">35</td>
<td styleCode="Rrule">0.3</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Rash <footnote>Includes rash, erythematous rash, maculo-papular rash, pruritic rash </footnote>
</td>
<td styleCode="Rrule">16</td>
<td styleCode="Rrule">0.6</td>
<td styleCode="Rrule">10</td>
<td styleCode="Rrule">0.3</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Skin hyperpigmentation <footnote>Includes pigmentation disorder, skin discoloration, skin hyperpigmentation</footnote>
</td>
<td styleCode="Rrule">10</td>
<td styleCode="Rrule">0</td>
<td styleCode="Rrule">0.3</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">General Disorders </content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Fatigue <footnoteRef IDREF="t4fa"/>
</td>
<td styleCode="Rrule">36</td>
<td styleCode="Rrule">2.8</td>
<td styleCode="Rrule">32</td>
<td styleCode="Rrule">2.9</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Eye Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Keratitis <footnote>Includes corneal disorder, corneal epithelium defect, corneal erosion, corneal exfoliation, corneal lesion, corneal toxicity, injury corneal, keratitis, keratopathy, punctate keratitis, ulcerative keratitis </footnote>
</td>
<td styleCode="Rrule">26</td>
<td styleCode="Rrule">6</td>
<td styleCode="Rrule">2.8</td>
<td styleCode="Rrule">0.3</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Dry eye</td>
<td styleCode="Rrule">26</td>
<td styleCode="Rrule">1.3</td>
<td styleCode="Rrule">4.9</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Musculoskeletal and connective tissue disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Musculoskeletal pain <footnoteRef IDREF="t4fa"/>
</td>
<td styleCode="Rrule">22</td>
<td styleCode="Rrule">0.6</td>
<td styleCode="Rrule">22</td>
<td styleCode="Rrule">1.3</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Cough <footnoteRef IDREF="t4fa"/>
</td>
<td styleCode="Rrule">19</td>
<td styleCode="Rrule">0</td>
<td styleCode="Rrule">14</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</td>
</tr>
<tr>
<td styleCode="Lrule Rrule"> Decreased appetite</td>
<td styleCode="Rrule">19</td>
<td styleCode="Rrule">0.6</td>
<td styleCode="Rrule">8</td>
<td styleCode="Rrule">0.3</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions including anaphylactic reaction, diarrhea, conjunctivitis, lacrimation increased, dry mouth, dry skin, pruritus, rhinorrhea, blepharitis, meibomian gland dysfunction, blurred vision, ILD/pneumonitis, visual impairment, photophobia, and madarosis.</paragraph>
<table ID="Table7" width="90%">
<caption>Table 7: Select Laboratory Abnormalities (≥20%) in Patients Who Received DATROWAY in TROPION-Breast02</caption>
<col align="left" valign="middle" width="32%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<thead>
<tr styleCode="Botrule">
<th align="center" rowspan="2" styleCode="Lrule Rrule">Laboratory Abnormality</th>
<th colspan="2" styleCode="Rrule">DATROWAY <footnote ID="t5fa">The denominator used to calculate the rate varied from 235 to 317 based on the number of patients with a baseline value and at least one post-treatment value. </footnote>
</th>
<th colspan="2" styleCode="Rrule" valign="top">Chemotherapy <footnoteRef IDREF="t5fa"/>
</th>
</tr>
<tr>
<th align="center" styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4 <br/>%</th>
<th styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4 <br/>%</th>
</tr>
</thead>
<tfoot>
<tr>
<td align="left" colspan="5" valign="top">Frequencies were based on NCI CTCAE v5.0 grade-derived laboratory abnormalities.</td>
</tr>
</tfoot>
<tbody>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Hematology</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased hemoglobin </td>
<td styleCode="Rrule">43</td>
<td styleCode="Rrule">3.8</td>
<td styleCode="Rrule">63</td>
<td styleCode="Rrule">6</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased white blood cells </td>
<td styleCode="Rrule">41</td>
<td styleCode="Rrule">0.9</td>
<td styleCode="Rrule">58</td>
<td styleCode="Rrule">10</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased lymphocytes</td>
<td styleCode="Rrule">36</td>
<td styleCode="Rrule">6</td>
<td styleCode="Rrule">46</td>
<td styleCode="Rrule">7</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased neutrophils</td>
<td styleCode="Rrule">35</td>
<td styleCode="Rrule">3.5</td>
<td styleCode="Rrule">48</td>
<td styleCode="Rrule">14</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Chemistry</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Increased amylase</td>
<td styleCode="Rrule">54</td>
<td styleCode="Rrule">38</td>
<td styleCode="Rrule">8</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased calcium </td>
<td styleCode="Rrule">39</td>
<td styleCode="Rrule">1.9</td>
<td styleCode="Rrule">44</td>
<td styleCode="Rrule">1.0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Increased ALT</td>
<td styleCode="Rrule">28</td>
<td styleCode="Rrule">1.6</td>
<td styleCode="Rrule">26</td>
<td styleCode="Rrule">1.3</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Increased AST</td>
<td styleCode="Rrule">27</td>
<td styleCode="Rrule">1.6</td>
<td styleCode="Rrule">26</td>
<td styleCode="Rrule">1.3</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased albumin</td>
<td styleCode="Rrule">25</td>
<td styleCode="Rrule">1.0</td>
<td styleCode="Rrule">20</td>
<td styleCode="Rrule">0.3</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased sodium</td>
<td styleCode="Rrule">21</td>
<td styleCode="Rrule">3.5</td>
<td styleCode="Rrule">18</td>
<td styleCode="Rrule">2.7</td>
</tr>
<tr>
<td styleCode="Lrule Rrule"> Increased blood alkaline phosphatase</td>
<td styleCode="Rrule">20</td>
<td styleCode="Rrule">0.3</td>
<td styleCode="Rrule">15</td>
<td styleCode="Rrule">0</td>
</tr>
</tbody>
</table>
<paragraph styleCode="underline">Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer </paragraph>
<paragraph styleCode="italics">TROPION-Breast01 </paragraph>
<paragraph>The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast01 <content styleCode="italics">[see <linkHtml href="#S14.3">Clinical Studies (14.3)</linkHtml>]</content>. DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 6.7 months (range: 0.7 months to 16.1 months) for patients who received DATROWAY.</paragraph>
<paragraph>Serious adverse reactions occurred in 15% of patients who received DATROWAY. Serious adverse reactions in >0.5% of patients who received DATROWAY were urinary tract infection (1.9%), COVID-19 infection (1.7%), ILD/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of patients who received DATROWAY and were due to ILD/pneumonitis.</paragraph>
<paragraph>Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 3.1% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (1.7%) and fatigue (0.6%). </paragraph>
<paragraph>Dosage interruptions of DATROWAY due to an adverse reaction occurred in 22% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (3.3%), infusion-related reaction (1.4%), ILD/pneumonitis (1.9%), stomatitis (1.9%), fatigue (1.7%), keratitis (1.4%), acute kidney injury (1.1%), and pneumonia (1.1%).</paragraph>
<paragraph>Dose reductions of DATROWAY due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (13%), fatigue (3.1%), nausea (2.5%), and weight decrease (1.9%).</paragraph>
<paragraph>The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase. </paragraph>
<table ID="Table8" width="90%">
<caption>Table 8: Adverse Reactions (≥10%) in Patients Who Received DATROWAY in TROPION-Breast01</caption>
<col align="left" valign="middle" width="32%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<thead>
<tr styleCode="Botrule">
<th align="center" rowspan="2" styleCode="Lrule Rrule">Adverse Reactions</th>
<th colspan="2" styleCode="Rrule">DATROWAY<br/>N=360</th>
<th colspan="2" styleCode="Rrule">Chemotherapy<br/>N=351</th>
</tr>
<tr>
<th align="center" styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4<br/>%</th>
<th styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3 or 4<br/>%</th>
</tr>
</thead>
<tfoot>
<tr>
<td align="left" colspan="5" valign="top">Events were graded using NCI CTCAE v5.0.</td>
</tr>
</tfoot>
<tbody>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Gastrointestinal Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Stomatitis <footnote ID="t8fa">Includes other related terms.</footnote>
</td>
<td styleCode="Rrule">59</td>
<td styleCode="Rrule">7</td>
<td styleCode="Rrule">17</td>
<td styleCode="Rrule">2.6</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Nausea</td>
<td styleCode="Rrule">56</td>
<td styleCode="Rrule">1.4</td>
<td styleCode="Rrule">27</td>
<td styleCode="Rrule">0.6</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Constipation</td>
<td styleCode="Rrule">34</td>
<td styleCode="Rrule">0.3</td>
<td styleCode="Rrule">17</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Vomiting</td>
<td styleCode="Rrule">24</td>
<td styleCode="Rrule">1.1</td>
<td styleCode="Rrule">12</td>
<td styleCode="Rrule">1.1</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Diarrhea</td>
<td styleCode="Rrule">11</td>
<td styleCode="Rrule">0.6</td>
<td styleCode="Rrule">19</td>
<td styleCode="Rrule">1.4</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Abdominal pain <footnoteRef IDREF="t8fa"/>
</td>
<td styleCode="Rrule">11</td>
<td styleCode="Rrule">0.6</td>
<td styleCode="Rrule">15</td>
<td styleCode="Rrule">1.4</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">General Disorders and Administration Site Conditions</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Fatigue <footnote>Includes fatigue, asthenia, lethargy, malaise</footnote>
</td>
<td styleCode="Rrule">44</td>
<td styleCode="Rrule">4.2</td>
<td styleCode="Rrule">40</td>
<td styleCode="Rrule">3.7</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Alopecia</td>
<td styleCode="Rrule">38</td>
<td styleCode="Rrule">0</td>
<td styleCode="Rrule">22</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Rash <footnoteRef IDREF="t8fa"/>
</td>
<td styleCode="Rrule">19</td>
<td styleCode="Rrule">0</td>
<td styleCode="Rrule">17</td>
<td styleCode="Rrule">2.3</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Eye Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Dry eye</td>
<td styleCode="Rrule">27</td>
<td styleCode="Rrule">0.8</td>
<td styleCode="Rrule">13</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Keratitis <footnote>Includes corneal disorder, corneal erosion, corneal infiltrates, corneal lesion, corneal toxicity, injury corneal, keratitis, keratopathy, punctate keratitis, and ulcerative keratitis</footnote>
</td>
<td styleCode="Rrule">24</td>
<td styleCode="Rrule">1.1</td>
<td styleCode="Rrule">10</td>
<td styleCode="Rrule">0</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Metabolism and Nutrition Disorders</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased appetite</td>
<td styleCode="Rrule">16</td>
<td styleCode="Rrule">1.4</td>
<td styleCode="Rrule">16</td>
<td styleCode="Rrule">0.9</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Infections and Infestations</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> COVID-19 <footnoteRef IDREF="t4fa"/>
</td>
<td styleCode="Rrule">16</td>
<td styleCode="Rrule">1.4</td>
<td styleCode="Rrule">13</td>
<td styleCode="Rrule">0.9</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders</content>
</td>
</tr>
<tr>
<td styleCode="Lrule Rrule"> Cough <footnoteRef IDREF="t4fa"/>
</td>
<td styleCode="Rrule">15</td>
<td styleCode="Rrule">0</td>
<td styleCode="Rrule">10</td>
<td styleCode="Rrule">0</td>
</tr>
</tbody>
</table>
<paragraph>Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions (including bronchospasm), ILD/pneumonitis, headache, pruritus, dry skin, dry mouth, conjunctivitis, blepharitis, meibomian gland dysfunction, blurred vision, increased lacrimation, photophobia, visual impairment, skin hyperpigmentation, and madarosis.</paragraph>
<table ID="Table9" width="90%">
<caption>Table 9: Select Laboratory Abnormalities (≥20%) in Patients Who Received DATROWAY in TROPION-Breast01</caption>
<col align="left" valign="middle" width="32%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<col align="center" valign="middle" width="17%"/>
<thead>
<tr styleCode="Botrule">
<th align="center" rowspan="2" styleCode="Lrule Rrule">Laboratory Abnormality</th>
<th colspan="2" styleCode="Rrule">DATROWAY <footnote ID="t9fa">The denominator used to calculate the rate varied from 264 to 359 based on the number of patients with a baseline value and at least one post-treatment value. </footnote>
</th>
<th colspan="2" styleCode="Rrule" valign="top">Chemotherapy <footnoteRef IDREF="t9fa"/>
</th>
</tr>
<tr>
<th align="center" styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3-4<br/>%</th>
<th styleCode="Rrule">All Grades<br/>%</th>
<th styleCode="Rrule">Grades 3-4<br/>%</th>
</tr>
</thead>
<tfoot>
<tr>
<td align="left" colspan="5" valign="top">Frequencies were based on NCI CTCAE v5.0 grade-derived laboratory abnormalities.</td>
</tr>
</tfoot>
<tbody>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Hematology</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased leukocytes</td>
<td styleCode="Rrule">41</td>
<td styleCode="Rrule">1.1</td>
<td styleCode="Rrule">63</td>
<td styleCode="Rrule">18</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased lymphocytes</td>
<td styleCode="Rrule">36</td>
<td styleCode="Rrule">9</td>
<td styleCode="Rrule">42</td>
<td styleCode="Rrule">11</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased hemoglobin </td>
<td styleCode="Rrule">35</td>
<td styleCode="Rrule">2.8</td>
<td styleCode="Rrule">51</td>
<td styleCode="Rrule">4.4</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased neutrophils</td>
<td styleCode="Rrule">30</td>
<td styleCode="Rrule">1.6</td>
<td styleCode="Rrule">61</td>
<td styleCode="Rrule">35</td>
</tr>
<tr styleCode="Botrule">
<td colspan="5" styleCode="Lrule Rrule">
<content styleCode="bold">Chemistry</content>
</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Decreased calcium </td>
<td styleCode="Rrule">39</td>
<td styleCode="Rrule">1.4</td>
<td styleCode="Rrule">43</td>
<td styleCode="Rrule">1.2</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Increased AST</td>
<td styleCode="Rrule">23</td>
<td styleCode="Rrule">1.9</td>
<td styleCode="Rrule">28</td>
<td styleCode="Rrule">0.9</td>
</tr>
<tr styleCode="Botrule">
<td styleCode="Lrule Rrule"> Increased ALT</td>
<td styleCode="Rrule">24</td>
<td styleCode="Rrule">1.7</td>
<td styleCode="Rrule">31</td>
<td styleCode="Rrule">0.6</td>
</tr>
<tr>
<td styleCode="Lrule Rrule"> Increased alkaline phosphatase</td>
<td styleCode="Rrule">23</td>
<td styleCode="Rrule">0.6</td>
<td styleCode="Rrule">20</td>
<td styleCode="Rrule">0.6</td>
</tr>
</tbody>
</table>
</text>
<effectiveTime value="20260527"/>
</section>
</component>
</section>
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