Adverse Reactions (ARs) Were Consistent With the Known Safety Profiles of TECENTRIQ and COTELLIC® (cobimetinib) + ZELBORAF® (vemurafenib) 1,3

ARs occurring in ≥10% of patients with between-arm differences of ≥5% for all grades or ≥2% for grades 3 to 4 

Laboratory abnormalities worsening from baseline occurring in ≥20% of patients with between-arm differences of ≥5% for all grades or ≥2% for grades 3 to 4 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 + COTELLIC + ZELBORAF (28-277), placebo + COTELLIC + ZELBORAF (25-230).
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; NA=not applicable.
*Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0).
Includes rash, rash maculopapular, dermatitis acneiform, rash macular, rash erythematous, eczema, skin exfoliation, rash papular, rash pustular, palmar-plantar erythrodysesthesia syndrome, dermatitis, dermatitis contact, erythema multiforme, rash pruritic, drug eruption, nodular rash, dermatitis allergic, exfoliative rash, dermatitis exfoliative generalized, and rash morbilliform.
Includes fatigue, asthenia, and malaise.
§Includes pyrexia and hyperpyrexia.
||Includes edema peripheral, lymphoedema, edema, face edema, eyelid edema, periorbital edema, lip edema, and generalized edema.
Includes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, transaminases increased, hepatitis, hepatic enzyme increased, hepatotoxicity, hypertransaminasemia, bilirubin conjugated increased, hepatocellular injury, hyperbilirubinemia, liver function test increased, hepatic failure, hepatitis fulminant, and liver function test abnormal.
#Includes stomatitis, mucosal inflammation, aphthous ulcer, mouth ulceration, cheilitis, and glossitis.
**Includes arthralgia, myalgia, pain in extremity, back pain, musculoskeletal pain, arthritis, neck pain, musculoskeletal chest pain, musculoskeletal stiffness, bone pain, spinal pain, immune-mediated arthritis, joint stiffness, and noncardiac chest pain.
††Includes hypothyroidism and blood thyroid-stimulating hormone increased.
‡‡Includes infusion-related reaction and hypersensitivity.
aIncludes pneumonitis and interstitial lung disease.
bIncludes hypertension, blood pressure increased, and hypertensive crisis.
cNCI CTCAE v4.0 does not include these laboratories.
dIncreased thyroid-stimulating hormone has a difference of <5% (all grades) between arms and is included for clinical completeness.

Additional ARs in IMspire150 1

  • Fatal ARs occurred in 3% of patients in the TECENTRIQ + COTELLIC + ZELBORAF arm. ARs leading to death were hepatic failure, fulminant hepatitis, sepsis, septic shock, pneumonia, and cardiac arrest
  • Serious ARs occurred in 45% of patients in the TECENTRIQ + COTELLIC + ZELBORAF arm. The most frequent (≥2%) serious ARs were hepatotoxicity (7%), pyrexia (6%), pneumonia (4.3%), malignant neoplasms (2.2%), and acute kidney injury (2.2%) 
  • ARs leading to discontinuation of TECENTRIQ occurred in 21% of patients in the TECENTRIQ + COTELLIC + ZELBORAF arm. The most frequent (≥2%) ARs leading to discontinuation were increased ALT (2.2%) and pneumonitis (2.6%)
  • ARs leading to interruption of TECENTRIQ occurred in 68% of patients in the TECENTRIQ + COTELLIC + ZELBORAF arm. The most frequent (≥2%) ARs leading to TECENTRIQ interruption were pyrexia (14%), increased ALT (13%), hyperthyroidism (10%), increased AST (10%), increased lipase (9%), increased amylase (7%), pneumonitis (5%), increased CPK (4.3%), diarrhea (3.5%), pneumonia (3.5%), asthenia (3%), rash (3%), influenza (3%), arthralgia (2.6%), fatigue (2.2%), dyspnea (2.2%), cough (2.2%), peripheral edema (2.2%), uveitis (2.2%), bronchitis (2.2%), hypothyroidism (2.2%), and respiratory tract infection (2.2%)

Discontinuation of all treatment due to ARs was 13% vs 16% in patients treated with placebo + COTELLIC + ZELBORAF 3