ZEPZELCA

5 WARNINGS AND PRECAUTIONS • Myelosuppression : Monitor blood counts prior to each administration. Initiate treatment with ZEPZELCA only if baseline neutrophil count is ≥ 1,500 cells/mm 3 and platelet count is ≥ 100,000/mm 3 . For neutrophil count less than 500 cells/mm 3 or any value less than lower limit of normal, administer G-CSF. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.1 ) • Hepatotoxicity : Monitor liver function tests prior to initiating ZEPZELCA, periodically during treatment and as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.2 ) • Extravasation Resulting in Tissue Necrosis : Consider use of a central venous catheter to reduce the risk of extravasation. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. ( 5.3 ) • Rhabdomyolysis : Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ( 5.4 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus and to use an effective method of contraception. ( 5.5 ) 5.1 Myelosuppression ZEPZELCA can cause severe and fatal myelosuppression including febrile neutropenia and sepsis, thrombocytopenia and anemia. Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm 3 and platelet count of at least 100,000/mm 3 . To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF) [refer to Prescribing Information] . Monitor blood counts including neutrophils, red blood cells and platelets prior to each ZEPZELCA administration. For neutrophil count less than 500 cells/mm 3 or any value less than lower limit of normal, administer G-CSF. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity [see Dosage and Administration (2.2) ] . ZEPZELCA with Intravenous Atezolizumab In the IMforte study [see Adverse Reactions (6.1) ] , primary prophylaxis of G-CSF was administered to 84% of patients. Based on laboratory values, decreased neutrophils occurred in 36%, including 18% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased neutrophil cells was 31 days and a median duration of 10 days. Febrile neutropenia occurred in 1.7%. Sepsis occurred in 1%. There were 7 fatal infections: pneumonia (n=3), sepsis (n=3), and febrile neutropenia (n=1). Based on laboratory values, decreased platelets occurred in 54%, including 15% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased platelet cells was 31 days and a median duration of 12 days. Based on laboratory values, decreased hemoglobin occurred in 51%, including 13% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased hemoglobin was 64 days and a median duration of 8 days. ZEPZELCA as a Single Agent In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent [see Adverse Reactions (6.1) ] , Grade 3 or 4 neutropenia occurred in 41% of patients, with a median time to onset of 15 days and a median duration of 7 days. Febrile neutropenia occurred in 7% of patients. Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients. 5.2 Hepatotoxicity ZEPZELCA can cause hepatotoxicity which may be severe. Monitor liver function tests prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity [see Dosage and Administration (2.2) ]. ZEPZELCA with Intravenous Atezolizumab In the IMforte study [see Adverse Reactions (6.1) ] , based on laboratory values, increased alanine aminotransferase (ALT) occurred in 25%, including 3% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. Increased aspartate aminotransferase (AST) occurred in 24% including 3% Grade 3 or Grade 4. The median time to onset of Grade ≥ 3 elevation in transaminases was 52 days (range: 6 to 337). ZEPZELCA as a Single Agent In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent [see Adverse Reactions (6.1) ] , Grade 3 elevations of ALT and AST were observed in 6% and 3% of patients, respectively, and Grade 4 elevations of ALT and AST were observed in 0.4% and 0.5% of patients, respectively. The median time to onset of Grade ≥ 3 elevation in transaminases was 8 days (range: 3 to 49), with a median duration of 7 days. 5.3 Extravasation Resulting in Tissue Necrosis Extravasation of ZEPZELCA can cause skin and soft tissue injury, including necrosis requiring debridement. Consider use of a central venous catheter to reduce the risk of extravasation, particularly in patients with limited venous access. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary. ZEPZELCA with Intravenous Atezolizumab In the IMforte study [see Adverse Reactions (6.1 )] , extravasation resulting in skin necrosis occurred in one patient who received ZEPZELCA in combination with atezolizumab. Administer supportive care and consult with an appropriate medical specialist as needed for signs and symptoms of extravasation. Administer subsequent infusions at a site that was not affected by extravasation. 5.4 Rhabdomyolysis Rhabdomyolysis has been reported in patients treated with ZEPZELCA. Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold or reduce the dose based on severity [see Dosage and Administration (2.2) ] . ZEPZELCA with Intravenous Atezolizumab In the IMforte study [see Adverse Reactions (6.1 )] , among 235 patients who had a creatine phosphokinase laboratory evaluation, increased creatine phosphokinase occurred in 9% who received ZEPZELCA in combination with atezolizumab. 5.5 Embryo-Fetal Toxicity Based on animal data and its mechanism of action ZEPZELCA can cause fetal harm when administered to a pregnant woman. Intravenous administration of a single dose of lurbinectedin (approximately 0.2 times the 3.2 mg/m 2 clinical dose) to pregnant animals during the period of organogenesis caused 100% embryolethality in rats. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose [see Use in Specific Populations (8.1 , 8.3 )] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Myelosuppression [see Warnings and Precautions (5.1) ] • Hepatotoxicity [see Warnings and Precautions (5.2) ] • Extravasation Resulting in Tissue Necrosis [see Warnings and Precautions (5.3) ] • Rhabdomyolysis [see Warnings and Precautions (5.4) ] The most common adverse reactions for ZEPZELCA as a single agent, including laboratory abnormalities, (≥ 20%) are leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea. ( 6.1 ) The most common adverse reactions, for ZEPZELCA in combination with atezolizumab including laboratory abnormalities, (≥ 30%) are: decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased neutrophils, nausea, and fatigue/asthenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals, Inc. at 1-800-520-5568 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 safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to ZEPZELCA in combination with intravenous atezolizumab in the IMforte study [see Clinical Studies (14.1) ] , in 242 patients with extensive stage small cell lung cancer (ES-SCLC) whose disease had not progressed after initial therapy with atezolizumab, carboplatin, and etoposide. Patients received ZEPZELCA 3.2 mg/m 2 intravenously (IV) in combination with atezolizumab 1200 mg IV every 21 days until disease progression or unacceptable toxicity. Among 242 patients who received ZEPZELCA in combination with intravenous atezolizumab, 34% were exposed for 6 months or longer and 8% were exposed for greater than one year. The most common adverse reactions (≥ 30%), including laboratory abnormalities, in patients who received ZEPZELCA with atezolizumab were decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased neutrophils, nausea, and fatigue/asthenia. The pooled safety population described in the WARNINGS AND PRECAUTIONS also reflects exposure to ZEPZELCA as a single agent at a dose of 3.2 mg/m 2 intravenously every 21 days in 554 patients with advanced solid tumors. Among 554 patients who received ZEPZELCA, including 105 patients with small cell lung cancer (SCLC) in PM1183-B-005-14 (Study B-005), 24% were exposed for 6 months or longer and 5% were exposed for greater than one year. The most common adverse reactions for ZEPZELCA as a single agent, (Study B-005), including laboratory abnormalities, (≥ 20%) are leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea. Extensive-Stage Small Cell Lung Cancer (IMforte) The safety of ZEPZELCA in combination with intravenous (IV) atezolizumab was evaluated in IMforte [see Clinical Studies (14) ] . Patients received intravenous ZEPZELCA 3.2 mg/m 2 in combination with intravenous atezolizumab 1200 mg on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. Primary prophylaxis of G-CSF was administered to 84% of patients. Among 242 patients who received ZEPZELCA with atezolizumab, the median duration of exposure to lurbinectedin was 4.1 months, 33% were exposed for 6 months or longer and 8% were exposed for greater than one year. The median age of patients who received ZEPZELCA in combination with intravenous atezolizumab was 66 years (range: 35 to 85); 62% male; 82% White, 13% Asian, and 0.8% Black or African American. Serious adverse reactions occurred in 31% of patients receiving ZEPZELCA in combination with atezolizumab. Serious adverse reactions occurring in > 2% were pneumonia (2.5%), respiratory tract infection (2.1%), dyspnea (2.1%), and decreased platelet count (2.1%). Fatal adverse reactions occurred in 5% of patients receiving ZEPZELCA with atezolizumab including pneumonia (3 patients), sepsis (3 patients), cardio-respiratory arrest (2 patients), myocardial infarction (2 patients), and febrile neutropenia (1 patient). Permanent discontinuation of ZEPZELCA due to an adverse reaction occurred in 5% of patients. The adverse reaction resulting in permanent discontinuation in ≥ 1% of patients who received ZEPZELCA was decreased neutrophil count. Dosage interruptions of ZEPZELCA due to an adverse reaction occurred in 25%. Adverse reactions which required dosage interruption in ≥ 2% of patients included anemia, fatigue, decreased neutrophil count, and decreased platelet count. Dose reductions of ZEPZELCA due to an adverse reaction occurred in 15% of patients. Adverse reactions which required dosage reduction in ≥ 2% of patients included decreased platelet count, fatigue, nausea and vomiting. Table 3 summarizes the adverse reactions in IMforte. Table 3: Adverse Reactions (≥ 10%) in Patients with ES-SCLC Who Received ZEPZELCA in Combination with Intravenous Atezolizumab in IMforte Graded per NCI CTCAE v5.0 1 Includes diarrhea and colitis. 2 Includes fatigue and asthenia. 3 Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and pain in extremity. 4 Includes cough, productive cough, and upper-airway cough syndrome. 5 Includes dyspnea and dyspnea exertional. Adverse Reaction ZEPZELCA with Atezolizumab N = 242 Atezolizumab N = 240 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal Nausea 36 3 4 1 Diarrhea 1 15 0 8 0 Vomiting 14 1 3 0 Constipation 12 0 6 1 General disorders and administration site conditions Fatigue 2 32 5 13 2 Musculoskeletal and connective tissue disorders Musculoskeletal Pain 3 19 2 16 1 Metabolism and Nutrition Decreased appetite 17 0 7 0 Respiratory, thoracic and mediastinal disorders Cough 4 12 0 8 0 Dyspnea 5 11 2 10 2 Clinically relevant adverse reactions in < 10% of patients who received ZEPZELCA in combination with intravenous atezolizumab included pneumonia, phlebitis, extravasation resulting in skin necrosis, hypersensitivity, and increased creatine phosphokinase. Table 4 summarizes the laboratory abnormalities in IMforte. Table 4: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with ES‑SCLC Who Received ZEPZELCA in Combination with Intravenous Atezolizumab in IMforte Graded per NCI CTCAE v5.0. Laboratory Abnormality ZEPZELCA with Atezolizumab N = 242 Atezolizumab N = 240 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Decreased lymphocytes 55 17 31 11 Decreased platelets 54 15 15 3 Decreased hemoglobin 51 13 12 3 Decreased neutrophils 36 18 7 4 Chemistry Increased alkaline phosphatase 29 1 14 0 Decreased sodium 27 4 30 5 Increased ALT 25 3 18 2 Increased AST 24 3 22 1 Decreased calcium 24 3 8 1 Increased creatinine 21 3 14 0 Metastatic Small Cell Lung Cancer (SCLC) (Study B-005) The safety of ZEPZELCA was evaluated in a cohort of 105 patients with previously treated SCLC in Study B-005 [ see Clinical Studies (14) ] . Patients received ZEPZELCA 3.2 mg/m 2 intravenously every 21 days. All patients in this study received a pre-specified anti-emetic regimen consisting of a corticosteroid and serotonin antagonist. Patients could receive G-CSF for secondary prophylaxis (i.e., after patients had an initial decrease in WBC), but not primary prophylaxis. Among patients who received ZEPZELCA, 29% were exposed for 6 months or longer and 6% were exposed for greater than one year. Serious adverse reactions occurred in 34% of patients who received ZEPZELCA. Serious adverse reactions in ≥ 3% of patients included pneumonia, febrile neutropenia, neutropenia, respiratory tract infection, anemia, dyspnea, and thrombocytopenia. Permanent discontinuation due to an adverse reaction occurred in two patients (1.9%) who received ZEPZELCA. Adverse reactions resulting in permanent discontinuation in ≥ 1% of patients who received ZEPZELCA, which included peripheral neuropathy and myelosuppression. Dosage interruptions due to an adverse reaction occurred in 30.5% of patients who received ZEPZELCA. Adverse reactions requiring dosage interruption in ≥ 3% of patients who received ZEPZELCA included neutropenia, and hypoalbuminemia. Dose reductions due to an adverse reaction occurred in 25% of patients who received ZEPZELCA. Adverse reactions requiring dosage reductions in ≥ 3% of patients who received ZEPZELCA included neutropenia, febrile neutropenia and fatigue. The most common adverse reactions, including laboratory abnormalities, (≥ 20%) were leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea. Table 5 summarizes the adverse reactions in the SCLC cohort of Study B-005. Table 5: Adverse Reactions (≥ 10%) in Patients with SCLC Who Received ZEPZELCA in Study B-005 a Graded per NCI CTCAE 4.0. b No grade 5 adverse reactions were reported. c Includes abdominal pain, abdominal pain upper and abdominal discomfort. d Includes musculoskeletal pain, back pain, arthralgia, pain in extremity, musculoskeletal chest pain, neck pain, bone pain and myalgia. e Includes cough and productive cough. f Includes upper respiratory tract infection, viral upper respiratory tract infection, respiratory tract infection and bronchitis. g Includes pneumonia and lung infection. h Includes neuropathy peripheral, neuralgia, paresthesia, peripheral sensory neuropathy, hypoesthesia, and hyperesthesia. Adverse Reaction ZEPZELCA (n=105) All Grades a,b (%) Grades 3-4 (%) General disorders Fatigue 77 12 Pyrexia 13 0 Chest pain 10 0 Gastrointestinal disorders Nausea 37 0 Constipation 31 0 Vomiting 22 0 Diarrhea 20 4 Abdominal pain c 11 1 Musculoskeletal and connective tissue disorders Musculoskeletal pain d 33 4 Metabolism and nutrition disorders Decreased appetite 33 1 Respiratory, thoracic and mediastinal disorders Dyspnea 31 6 Cough e 20 0 Infections and infestations Respiratory tract infection f 18 5 Pneumonia g 10 7 Nervous system disorders Peripheral neuropathy h 11 1 Headache 10 1 Clinically relevant adverse reactions in < 10% of patients who received ZEPZELCA include dysgeusia, febrile neutropenia and pneumonitis. Table 6 summarizes the laboratory abnormalities in Study B-005. Table 6: Select Laboratory Abnormalities (≥ 20%) Worsening from Baseline in Patients with SCLC Who Received ZEPZELCA in Study B-005 a The denominator used to calculate the rate varied from 95 to 105 based on the number of patients with a baseline value and at least one post-treatment value. b Graded per NCI CTCAE 4.0. Laboratory Abnormality ZEPZELCA a (n=105) All Grades b (%) Grades 3-4 (%) Hematology Decreased leukocytes 79 29 Decreased lymphocytes 79 43 Decreased hemoglobin 74 10 Decreased neutrophils 71 46 Decreased platelets 37 7 Chemistry Increased creatinine 69 0 Increased alanine aminotransferase 66 4 Increased glucose 52 5 Decreased albumin 32 1 Decreased sodium 31 7 Increased aspartate aminotransferase 26 2 Decreased magnesium 22 0 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ZEPZELCA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General disorders and administration site conditions: Extravasation including tissue necrosis requiring debridement. Musculoskeletal and connective tissue disorders: Rhabdomyolysis. Metabolism and nutrition disorders: Tumor lysis syndrome.

<table styleCode="Noautorules" width="100%"><caption>Table 3: Adverse Reactions (&#x2265; 10%) in Patients with ES-SCLC Who Received ZEPZELCA in Combination with Intravenous Atezolizumab in IMforte</caption><col width="20%"/><col width="20%"/><col width="20%"/><col width="20%"/><col width="20%"/><tfoot><tr><td align="left" colspan="5" valign="top">Graded per NCI CTCAE v5.0</td></tr><tr><td align="left" colspan="5" valign="top">¹ Includes diarrhea and colitis.</td></tr><tr><td align="left" colspan="5" valign="top">² Includes fatigue and asthenia.</td></tr><tr><td align="left" colspan="5" valign="top">³ Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and pain in extremity.</td></tr><tr><td align="left" colspan="5" valign="top">⁴Includes cough, productive cough, and upper-airway cough syndrome.</td></tr><tr><td align="left" colspan="5" valign="top">⁵Includes dyspnea and dyspnea exertional. </td></tr></tfoot><tbody><tr><td 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">ZEPZELCA with Atezolizumab N = 242</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Atezolizumab N = 240</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 or 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 or 4 (%)</content></paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3</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>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea¹</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>0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8</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>Vomiting</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>1</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3</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>Constipation</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</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>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue²</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>5</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>2</paragraph></td></tr><tr><td colspan="5" 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>Musculoskeletal Pain³</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>19</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>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and Nutrition</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>17</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>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">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Cough⁴</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</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>8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Dyspnea⁵</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>2</paragraph></td></tr></tbody></table>

<table styleCode="Noautorules" width="100%"><caption>Table 4: Select Laboratory Abnormalities (&#x2265; 20%) That Worsened from Baseline in Patients with ES&#x2011;SCLC Who Received ZEPZELCA in Combination with Intravenous Atezolizumab in IMforte</caption><col width="29%"/><col width="20%"/><col width="18%"/><col width="12%"/><col width="20%"/><tfoot><tr><td align="left" colspan="5" valign="top">Graded per NCI CTCAE v5.0. </td></tr></tfoot><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Laboratory Abnormality</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">ZEPZELCA with Atezolizumab N = 242</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Atezolizumab N = 240</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 or 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 or 4 (%)</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>Decreased lymphocytes</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>55</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>31</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased platelets</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>54</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>15</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>Decreased hemoglobin</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>51</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>12</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>Decreased neutrophils</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</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>7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4</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>Increased alkaline phosphatase </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>1</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>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased sodium </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>4</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>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Increased ALT</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>3</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>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Increased AST</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>3</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</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased calcium</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>3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Increased creatinine</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0</paragraph></td></tr></tbody></table>

<table styleCode="Noautorules" width="98.98%"><caption>Table 5: Adverse Reactions (&#x2265; 10%) in Patients with SCLC Who Received ZEPZELCA in Study B-005</caption><col width="33%"/><col width="33%"/><col width="33%"/><tfoot><tr><td align="left" colspan="3" valign="top">^a Graded per NCI CTCAE 4.0.</td></tr><tr><td align="left" colspan="3" valign="top">^b No grade 5 adverse reactions were reported.</td></tr><tr><td align="left" colspan="3" valign="top">^c Includes abdominal pain, abdominal pain upper and abdominal discomfort.</td></tr><tr><td align="left" colspan="3" valign="top">^d Includes musculoskeletal pain, back pain, arthralgia, pain in extremity, musculoskeletal chest pain, neck pain, bone pain and myalgia. </td></tr><tr><td align="left" colspan="3" valign="top">^e Includes cough and productive cough.</td></tr><tr><td align="left" colspan="3" valign="top">^f Includes upper respiratory tract infection, viral upper respiratory tract infection, respiratory tract infection and bronchitis.</td></tr><tr><td align="left" colspan="3" valign="top">^g Includes pneumonia and lung infection.</td></tr><tr><td align="left" colspan="3" valign="top">^h Includes neuropathy peripheral, neuralgia, paresthesia, peripheral sensory neuropathy, hypoesthesia, and hyperesthesia. </td></tr></tfoot><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"><paragraph><content styleCode="bold">ZEPZELCA (n=105)</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">All Grades</content>^a,b<content styleCode="bold"> (%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph><content styleCode="bold">Grades 3-4 (%)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>77</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</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>13</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>Chest pain</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</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</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>Constipation</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>31</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>Vomiting</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>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Abdominal pain^c</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>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Musculoskeletal pain^d</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>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></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>33</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><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dyspnea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>31</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>Cough^e</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20</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><content styleCode="bold">Infections and infestations</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Respiratory tract infection^f</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>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pneumonia^g</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>7</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Peripheral neuropathy^h</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>1</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>1</paragraph></td></tr></tbody></table>