Table 5: Grades 3–4 Laboratory Abnormalities in ≥ 1% of Patients with Urothelial Carcinoma in IMvigor210 (Cohort 1) (continued)
Laboratory Abnormality Hyperglycemia
Increased Alkaline Phosphatase Increased Creatinine Hypophosphatemia Increased ALT Increased AST Hyperkalemia
Hypermagnesemia Hyperbilirubinemia
Hematology Lymphopenia Anemia
Graded per NCI CTCAE v4.0. Non-Small Cell Lung Cancer (NSCLC) Adjuvant Treatment of Early-stage NSCLC IMpower010
The safety of TECENTRIQ was evaluated in IMpower010, a multicenter, open-label, randomized trial for the adjuvant treatment of patients with stage IB (tumors ≥ 4 cm) - IIIA NSCLC who had complete tumor resection and received up to 4 cycles of cisplatin-based adjuvant chemotherapy. Patients received TECENTRIQ 1200 mg every 3 weeks (n=495) for 1 year (16 cycles), unless disease progression or unacceptable toxicity occurred, or best supportive care [see Clinical Studies (14.2)]. The median number of cycles received was 16 (range: 1, 16).
Fatal adverse reactions occurred in 1.8% of patients receiving TECENTRIQ; these included multiple organ dysfunction syndrome, pneumothorax, interstitial lung disease, arrhythmia, acute cardiac failure, myocarditis, cerebrovascular accident, death of unknown cause, and acute myeloid leukemia (1 patient each).
Serious adverse reactions occurred in 18% of patients receiving TECENTRIQ. The most frequent serious adverse reactions (>1%) were pneumonia (1.8%), pneumonitis (1.6%), and pyrexia (1.2%).
TECENTRIQ was discontinued due to adverse reactions in 18% of patients; the most common adverse reactions (≥1%) leading to TECENTRIQ discontinuation were pneumonitis (2.2%), hypothyroidism (1.6%), increased aspartate aminotranferase (1.4%), arthralgia (1.0%), and increased alanine aminotransferase (1.0%).
Adverse reactions leading to interruption of TECENTRIQ occurred in 29% of patients; the most common (>1%) were rash (3.0%), hyperthyroidism (2.8%), hypothyroidism (1.6%), increased AST (1.6%), pyrexia (1.6%), increased ALT (1.4%), upper respiratory tract infection (1.4%), headache (1.2%), peripheral neuropathy (1.2%), and pneumonia (1.2%).
Tables 6 and 7 summarize adverse reactions and selected laboratory abnormalities in patients receiving TECENTRIQ in IMpower010.
Table 6: Adverse Reactions Occurring in ≥10% of Patients with Early Stage NSCLC Receiving TECENTRIQ in IMpower010
Adverse Reaction*
Skin and Subcutaneous Tissue Rash1
Pruritus
Endocrine Disorders Hypothyroidism2
General Pyrexia4 Fatigue5
Nervous System Disorders Peripheral neuropathy6
TECENTRIQ N = 495
All Grades (%)
17 10
14
Respiratory, Thoracic and Mediastinal Cough3
16
14 14
12
Musculoskeletal and Connective Tissue Musculoskeletal pain7 Arthralgia8
14 11
*Graded per NCI CTCAE v4.0 1
2
Grades 3–4 (%)
1.2 0
0 0
0.8 0.6
0.4
0.8 0.6
Best Supportive Care N = 495
All Grades (%)
1.4 0.6
0.6 11
2.2 5
7
9 6
Grades 3–4 (%)
0 0
Laboratory Abnormality 0 0
0.2 0.2
0.2
0.2 0
Includes rash, dermatitis, genital rash, skin exfoliation, rash maculo-papular, rash erythematous, rash papular, lichen planus, eczema asteatotic, dermatitis exfoliative, palmar-plantar erythrodysaesthesia syndrome, dyshidrotic eczema, eczema, drug eruption, rash pruritic, toxic skin eruption, dermatitis acneiform
Includes hypothyroidism, autoimmune hypothyroidism, primary hypothyroidism, blood thyroid stimulating hormone increased
3 Productive cough, upper airway cough syndrome, cough 4 Includes pyrexia, body temperature increased, hyperthermia 5 Includes fatigue, asthenia
6 7
Includes paraesthesia, neuropathy peripheral, peripheral sensory neuropathy, hypoaesthesia, polyneuropathy, dysaesthesia, neuralgia, axonal neuropathy
Includes myalgia, bone pain, back pain, spinal pain, musculoskeletal chest pain, pain in extremity, neck pain, non- cardiac chest pain, musculoskeletal discomfort, musculoskeletal stiffness, musculoskeletal pain
8 Includes arthralgia, arthritis
Table 7: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients with Early Stage NSCLC Receiving TECENTRIQ in IMpower010
TECENTRIQ2 Laboratory Abnormality1 Chemistry
Increased aspartate aminotransferase
Increased alanine aminotransferase
Hyperkalemia Increased blood creatinine 34
30 24
31 2.5
3.3 3.5
0.2 18
19 15
23 0
0.4 2.5
0.2
All Grades (%)
Grades 3–4 (%)
Best Supportive Care2
All Grades (%)
Grades 3–4 (%)
Hematology Anemia
Lymphopenia
Increased alkaline phosphatase
Hyponatremia Increased ALT Increased AST Hyperkalemia Hypocalcemia
Increased blood creatinine Hypophosphatemia
Grades 3–4 (%)
10 7 5 4 4 4 3 3 3
9 7
1 2
Graded per NCI CTCAE v4.0, except for increased creatinine which only includes patients with creatinine increase based on upper limit of normal definition for Grade 1 events (NCI CTCAE v5.0).
The denominators used to calculate the rate varied from 78-480 for BSC arm and 483 for atezolizumab are for all tests of interest based on the number of patients with a baseline value and at least one post-treatment value.
Metastatic Chemotherapy-Naïve NSCLC IMpower110 The safety of TECENTRIQ was evaluated in IMpower110, a multicenter, international, randomized, open-label study in 549 chemotherapy-naïve patients with stage IV NSCLC, including those with EGFR or ALK genomic tumor aberrations. Patients received TECENTRIQ 1200 mg every 3 weeks (n=286) or platinum-based chemotherapy consisting of carboplatin or cisplatin with either pemetrexed or gemcitabine (n=263) until disease progression or unacceptable toxicity [see Clinical Studies (14.2)]. IMpower110 enrolled patients whose tumors express PD-L1 (PD-L1 stained ≥ 1% of tumor cells [TC] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 1% of the tumor area). The median duration of exposure to TECENTRIQ was 5.3 months (0 to 33 months). Fatal adverse reactions occurred in 3.8% of patients receiving TECENTRIQ; these included death (reported as unexplained death and death of unknown cause), aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infarction, and device occlusion (1 patient each). Serious adverse reactions occurred in 28% of patients receiving TECENTRIQ. The most frequent serious adverse reactions (>2%) were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%) and pneumonitis (2.1%). TECENTRIQ was discontinued due to adverse reactions in 6% of patients; the most common adverse reactions (≥2 patients) leading to TECENTRIQ discontinuation were peripheral neuropathy and pneumonitis. Adverse reactions leading to interruption of TECENTRIQ occurred in 26% of patients; the most common (>1%) were ALT increased (2.1%), AST increased (2.1%), pneumonitis (2.1%), pyrexia (1.4%), pneumonia (1.4%) and upper respiratory tract infection (1.4%). Tables 8 and 9 summarize adverse reactions and selected laboratory abnormalities in patients receiving TECENTRIQ in IMpower110.
Table 8: Adverse Reactions Occurring in ≥10% of Patients with NSCLC Receiving TECENTRIQ in IMpower110
Adverse Reaction
Gastrointestinal Nausea
Constipation Diarrhea
General Fatigue/asthenia Pyrexia
Metabolism and Nutrition Decreased appetite
TECENTRIQ N = 286
All Grades (%)
14 12 11
25 14
15
Respiratory, Thoracic and Mediastinal Dyspnea Cough
14 12
Graded per NCI CTCAE v4.0
Table 9: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients Receiving TECENTRIQ in IMpower110
TECENTRIQ
All Grades (%)
69 47
Chemistry Hypoalbuminemia 48
46 44
38 36 29 24 24 23
Grades 3–4 (%)
1.8 9
0.4 2.5
3.2 3.2 3.9 1.4 0.7 3.6
Platinum-Based Chemotherapy
All Grades (%)
94 59
39 42
Grades 3–4 (%)
20 17
2 1.2
9367 32 32 36 24 33 21
0.8 0.8 2.7 2.7 1.5 2
Each test incidence is based on the number of patients who had at least one on-study laboratory measurement available: TECENTRIQ (range: 278-281); platinum-based chemotherapy (range: 256-260). Graded per NCI CTCAE v4.0. Increased blood creatinine only includes patients with test results above the normal range.
IMpower150 The safety of TECENTRIQ with bevacizumab, paclitaxel and carboplatin was evaluated in IMpower150, a multicenter, international, randomized, open-label trial in which 393 chemotherapy-naïve patients with metastatic non-squamous NSCLC received TECENTRIQ 1200 mg with bevacizumab 15 mg/kg, paclitaxel 175 mg/m2
for a maximum of 4 or 6 cycles, followed by TECENTRIQ 1200 mg with bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity [see Clinical Studies (14.2)]. The median duration of exposure to TECENTRIQ was 8.3 months in patients receiving TECENTRIQ with bevacizumab, paclitaxel, and carboplatin. Fatal adverse reactions occurred in 6% of patients receiving TECENTRIQ; these included hemoptysis, febrile neutropenia, pulmonary embolism, pulmonary hemorrhage, death, cardiac arrest, cerebrovascular accident, pneumonia, aspiration pneumonia, chronic obstructive pulmonary disease, intracranial hemorrhage, intestinal angina, intestinal ischemia, intestinal obstruction and aortic dissection. Serious adverse reactions occurred in 44%. The most frequent serious adverse reactions (>2%) were febrile neutropenia, pneumonia, diarrhea, and hemoptysis. TECENTRIQ was discontinued due to adverse reactions in 15% of patients; the most common adverse reaction leading to discontinuation was pneumonitis (1.8%). Adverse reactions leading to interruption of TECENTRIQ occurred in 48%; the most common (>1%) were neutropenia, thrombocytopenia, fatigue/asthenia, diarrhea, hypothyroidism, anemia, pneumonia, pyrexia, hyperthyroidism, febrile neutropenia, increased ALT, dyspnea, dehydration and proteinuria.
or 200 mg/m2 , and carboplatin AUC 6 mg/mL/min intravenously every 3 weeks
Grades 3–4 (%)
0.3 1.0 0
1.4 0
0.7
0.7 0.3
Platinum-Based Chemotherapy N = 263
All Grades (%)
34 22 12
34 9
19
10 10
Grades 3–4 (%)
1.9 0.8 0.8
4.2 0.4
0
0 0
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