Previously Treated Metastatic NSCLC The safety of TECENTRIQ was evaluated in OAK, a multicenter, international, randomized, open-label trial in patients with metastatic NSCLC who progressed during or following a platinum-containing regimen, regardless of PD-L1 expression [see Clinical Studies (14.2)]. A total of 609 patients received TECENTRIQ 1200 mg intravenously every 3 weeks until unacceptable toxicity, radiographic progression, or clinical progression or docetaxel (n=578) 75 mg/m2
toxicity or disease progression. The study excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids. The median duration of exposure was 3.4 months (0 to 26 months) in TECENTRIQ-treated patients and 2.1 months (0 to 23 months) in docetaxel-treated patients.
intravenously every 3 weeks until unacceptable
The study population characteristics were: median age of 63 years (25 to 85 years), 46% age 65 years or older, 62% male, 71% White, 20% Asian, 68% former smoker, 16% current smoker, and 63% had ECOG performance status of 1.
Fatal adverse reactions occurred in 1.6% of patients; these included pneumonia, sepsis, septic shock, dyspnea, pulmonary hemorrhage, sudden death, myocardial ischemia or renal failure.
Serious adverse reactions occurred in 33.5% of patients. The most frequent serious adverse reactions (>1%) were pneumonia, sepsis, dyspnea,
respiratory tract infection. TECENTRIQ was discontinued due to adverse reactions in 8% of patients. The most common adverse reactions leading to TECENTRIQ discontinuation were fatigue, infections and dyspnea. Adverse reactions leading to interruption of TECENTRIQ occurred in 25% of patients; the most common (>1%) were pneumonia, liver function test abnormality, dyspnea, fatigue, pyrexia, and back pain. Tables 14 and 15 summarize adverse reactions and laboratory abnormalities, respectively, in OAK.
pleural effusion, pulmonary embolism, pyrexia and
Table 14: Adverse Reactions Occurring in ≥10% of Patients with NSCLC Receiving TECENTRIQ in OAK
Adverse Reaction
General Fatigue/Asthenia1 Pyrexia
Respiratory Cough2
Dyspnea
Metabolism and Nutrition Decreased appetite
Musculoskeletal Myalgia/Pain3 Arthralgia
Gastrointestinal Nausea
Constipation Diarrhea
Skin Rash4
Graded per NCI CTCAE v4.0 1
Includes fatigue and asthenia 2 Includes cough and exertional cough
3 Includes musculoskeletal pain, musculoskeletal stiffness, musculoskeletal chest pain, myalgia 4
Includes rash, erythematous rash, generalized rash, maculopapular rash, papular rash, pruritic rash, pustular rash, pemphigoid
Table 15: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients with NSCLC Receiving TECENTRIQ in OAK
TECENTRIQ Laboratory Abnormality
Hematology Anemia
Lymphocytopenia
All Grades (%)
67 49
Chemistry Hypoalbuminemia 48 Hyponatremia
Increased Alkaline Phosphatase
Increased AST Increased ALT
Hypophosphatemia Hypomagnesemia Increased Creatinine
42 39 31
27 27 26 23
Grades 3-4 (%)
3 14
4 7
Docetaxel
All Grades (%)
82 60
50 31
3 5
16 14 23
16
Grades 3-4 (%)
7 21
3 6
2251 3
0.5 0.5 4
1211 2
1
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: TECENTRIQ (range: 546–585) and docetaxel (range: 532–560). Graded according to NCI CTCAE version 4.0
Small Cell Lung Cancer (SCLC) The safety of TECENTRIQ with carboplatin and etoposide was evaluated in IMpower133, a randomized, multicenter, double-blind, placebo-controlled trial in which 198 patients with ES-SCLC received TECENTRIQ 1200 mg and carboplatin AUC 5 mg/mL/min on Day 1 and etoposide 100 mg/m2
Fatal adverse reactions occurred in 2% of patients receiving TECENTRIQ. These included pneumonia, respiratory failure, neutropenia, and death (1 patient each).
Serious adverse reactions occurred in 37% of patients receiving TECENTRIQ. Serious adverse reactions in >2% were pneumonia (4.5%), neutropenia (3.5%), febrile neutropenia (2.5%), and thrombocytopenia (2.5%).
TECENTRIQ was discontinued due to adverse reactions in 11% of patients. The most frequent adverse reaction requiring permanent discontinuation in >2% of patients was infusion-related reactions (2.5%).
Adverse reactions leading to interruption of TECENTRIQ occurred in 59% of patients; the most common (>1%) were neutropenia (22%), anemia (9%), leukopenia (7%), thrombocytopenia (5%), fatigue (4.0%), infusion-related reaction (3.5%), pneumonia (2.0%), febrile neutropenia (1.5%), increased ALT (1.5%), and nausea (1.5%).
Tables 16 and 17 summarize adverse reactions and laboratory abnormalities, respectively, in patients who received TECENTRIQ with carboplatin and etoposide in IMpower133.
on Days 1, 2 and 3 of each 21-day cycle for a maximum of 4 cycles, followed by TECENTRIQ 1200 mg every 3 weeks until disease progression or unacceptable toxicity [see Clinical Studies (14.3)]. Among 198 patients receiving TECENTRIQ, 32% were exposed for 6 months or longer and 12% were exposed for 12 months or longer.
intravenously
TECENTRIQ N = 609
All Grades (%)
44 18
26 22
23
20 12
18 18 16
12
Grades 3-4 (%)
4 <1
<1 2.8
<1
1.3 0.5
<1 <1 <1
<1
Docetaxel N = 578
All Grades (%)
53 13
21 21
24
20 10
23 14 24
10
Grades 3-4 (%)
Laboratory Abnormality 6 <1
<1 2.6
1.6
<1 0.2
<1 <1 2
0
Hematology Anemia
Neutropenia
Thrombocytopenia Lymphopenia
Chemistry Hyperglycemia
Increased Alkaline Phosphatase
Hyponatremia
Hypoalbuminemia Decreased TSH2 Hypomagnesemia Hypocalcemia Increased ALT Increased AST
Increased Blood Creatinine Hyperphosphatemia Increased TSH2
Table 16: Adverse Reactions Occurring in ≥20% of Patients with SCLC Receiving TECENTRIQ in IMpower133
Adverse Reaction
General Fatigue/asthenia
Gastrointestinal Nausea
Constipation Vomiting
Skin and Subcutaneous Tissue Alopecia
Metabolism and Nutrition Decreased appetite
Graded per NCI CTCAE v4.0
Table 17: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients with SCLC Receiving TECENTRIQ in IMpower133
TECENTRIQ with Carboplatin and Etoposide
All Grades (%)
94 73 58 46
67 38 34
32 28 31 26 26 22 22 21 21
Grades 3–4 (%)
17 45 20 14
10 1
15 1
NA1 5 3 3 1 4
NA1 NA1
Carboplatin and Etoposide
All Grades (%)
93 76 53 38
65 35 33
30 15 35 28 31 21 15 23
Grades 3–4 (%)
19 48 17 11
8 2
11 0
NA1 6 5 1 2 1
NA1 7NA1
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory NA = Not applicable. 2
measurement available: TECENTRIQ (range: 181-193); Placebo (range: 181-196). Graded per NCI CTCAE v4.0 1
TSH = thyroid-stimulating hormone. NCI CTCAE v4.0 does not include these laboratories.
Hepatocellular Carcinoma (HCC) The safety of TECENTRIQ in combination with bevacizumab was evaluated in IMbrave150, a multicenter, international, randomized, open-label trial in patients with locally advanced or metastatic or unresectable hepatocellular carcinoma who have not received prior systemic treatment [see Clinical Studies (14.4)]. Patients received 1,200 mg of TECENTRIQ intravenously followed by 15 mg/kg bevacizumab (n=329) every 3 weeks, or 400 mg of sorafenib (n=156) given orally twice daily, until disease progression or unacceptable toxicity. The median duration of exposure to TECENTRIQ was 7.4 months (range: 0-16 months) and to bevacizumab was 6.9 months (range: 0-16 months). Fatal adverse reactions occurred in 4.6% of patients in the TECENTRIQ and bevacizumab arm. The most common adverse reactions leading to death were gastrointestinal and esophageal varices hemorrhage (1.2%) and infections (1.2%). Serious adverse reactions occurred in 38% of patients in the TECENTRIQ and bevacizumab arm. The most frequent serious adverse reactions (≥ 2%) were gastrointestinal hemorrhage (7%), infections (6%), and pyrexia (2.1%). Adverse reactions leading to discontinuation of TECENTRIQ occurred in 9% of patients in the TECENTRIQ and bevacizumab arm. The most common adverse reactions leading to TECENTRIQ discontinuation were hemorrhages (1.2%), including gastrointestinal, subarachnoid, and pulmonary hemorrhages; increased transaminases or bilirubin (1.2%); infusion-related reaction/cytokine release syndrome (0.9%); and autoimmune hepatitis (0.6%). Adverse reactions leading to interruption of TECENTRIQ occurred in 41% of patients in the TECENTRIQ and bevacizumab arm; the most common (≥ 2%) were liver function laboratory abnormalities including increased transaminases, bilirubin, or alkaline phosphatase (8%); infections (6%); gastrointestinal hemorrhages (3.6%); thrombocytopenia/decreased platelet count (3.6%); hyperthyroidism (2.7%); and pyrexia (2.1%). Immune-related adverse reactions requiring systemic corticosteroid therapy occurred in 12% of patients in the TECENTRIQ and bevacizumab arm. Tables 18 and 19 summarize adverse reactions and laboratory abnormalities, respectively, in patients who received TECENTRIQ and bevacizumab in IMbrave150.
Placebo with
Carboplatin and Etoposide N = 198
All Grades (%)
39
38 26 20
37 27
Grades 3–4 (%)
5
1 1 2
0 1 TECENTRIQ with
Carboplatin and Etoposide N = 196
All Grades (%)
33
33 30 17
35 18
Grades 3–4 (%)
3
1 1 3
0 0 Placebo with
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