Applies to mobocertinib: oral capsules.

Side effects include:

The most common (>20%) adverse reactions are diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased amylase, increased lipase, decreased potassium, decreased hemoglobin, increased creatinine, and decreased magnesium.

For Healthcare Professionals

Applies to mobocertinib: oral capsule.

General

The most common adverse reactions in patients treated with this drug were diarrhea, rash, anemia, increased blood creatinine, nausea, stomatitis, increased amylase, vomiting, decreased appetite, increased lipase, fatigue, dry skin, paronychia, hypokalemia, hypomagnesemia, decreased platelet count, decreased WBC count, and musculoskeletal pain. Serious adverse reactions occurred in 46% of patients treated with this drug; the most common serious adverse reactions were diarrhea, dyspnea, vomiting, pneumonia, pyrexia, acute kidney injury, dehydration, nausea, pleural effusion, and cardiac failure; fatal adverse reactions occurred in 1.8% of patients, including cardiac failure and pneumonitis. Permanent discontinuation occurred in up to 19% of patients; adverse reactions requiring permanent discontinuation of therapy in at least 2% of patients were diarrhea and nausea. Dosage interruption due to an adverse reaction occurred in up to 61% of patients; adverse reactions which required dosage interruption in greater than 5% of patients included diarrhea, nausea, stomatitis, rash, and vomiting. Dose reductions due to an adverse reaction occurred in up to 32% of patients; adverse reactions which required dose reduction in greater than 5% of patients included diarrhea, nausea, and rash.^[Ref]

Cardiovascular

Very common (10% or more): Hypertension (includes hypertension, increased blood pressure; up to 14%)

Common (1% to 10%): QTc interval prolongation (includes ECG QT prolonged, ventricular arrhythmia), cardiac failure (includes cardiac failure, congestive cardiac failure, decreased ejection fraction, cardiomyopathy), atrial fibrillation

Uncommon (0.1% to 1%): Ventricular tachycardia, first-degree atrioventricular (AV) block, second-degree AV block, left bundle branch block, supraventricular extrasystoles, ventricular extrasystoles

Frequency not reported: Torsades de pointes, cardiac toxicity (including decreased ejection fraction, cardiomyopathy, congestive heart failure)^[Ref]

In patients treated with this drug, QTc interval prolongation occurred in 8% of patients; Grade 3 QTc interval prolongation occurred in 1.6% of patients and Grade 4 QTc interval prolongation (torsades de pointes) occurred in 0.4% of patients. In the 253-patient subset of the pooled safety population who had scheduled and unscheduled ECGs, 2.4% of patients had QTc interval greater than 500 msec and 13% of patients had a change-from-baseline QTc interval greater than 60 msec; on-treatment ECGs were not routinely performed in the first 28 days of therapy. The median time to onset of QTc interval prolongation was 66 days and the median time to resolution was 29 days.

In patients treated with this drug, cardiac failure/toxicity (including congestive cardiac failure, decreased ejection fraction, and cardiomyopathy) occurred in 2.3% of patients; Grade 3, Grade 4, and fatal cardiac failure occurred in 0.8%, 0.4%, and 0.4% of patients, respectively. The median time to onset of cardiac failure was 150 days and the median time to resolution was 13 days.^[Ref]

Dermatologic

Very common (10% or more): Rash (includes acne, dermatitis, acneiform dermatitis, rash, macular rash, maculopapular rash, papular rash, pruritic rash, pustular rash, urticaria, eczema, erythema, folliculitis; up to 78%), paronychia (includes nail bed tenderness, nail disorder, nail infection, onycholysis, paronychia; up to 39%), dry skin (includes dry skin, skin fissures, skin exfoliation; up to 32%), pruritus (up to 24%), alopecia (up to 19%)

Common (1% to 10%): Palmar-plantar erythrodysesthesia syndrome, urticaria^[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 93%), elevated pancreatic enzymes (amylase and lipase; up to 51%), nausea (up to 47%), stomatitis (includes angular cheilitis, aphthous ulcer, cheilitis, mouth ulceration, mucosal inflammation, odynophagia, stomatitis; up to 46%), increased amylase (up to 40%), vomiting (up to 40%), increased lipase (up to 35%), abdominal pain (includes abdominal discomfort, abdominal pain, upper abdominal pain, abdominal tenderness, gastrointestinal pain; up to 18%), gastroesophageal reflux disease (up to 15%), dyspepsia (up to 11%)^[Ref]

In clinical studies, 74% of patients experienced Grade 1 or 2 diarrhea; Grade 3 and 4 diarrhea occurred in 20% and 0.4% of patients, respectively. The median time to onset was 5 days and the median time to resolution was 3 days; resolution occurred in 48% of patients.

In patients treated with this drug, elevated pancreatic enzymes (amylase and lipase) occurred in 51% of patients; Grade 3 and 4 elevated pancreatic enzymes occurred in 14% and 3.9% of patients, respectively. The median time to onset was 30 days and the median time to resolution was 29 days.^[Ref]

Hematologic

Very common (10% or more): Anemia (up to 67%), decreased RBCs (up to 59%), decreased lymphocytes (up to 52%), decreased platelet count (up to 27%), decreased leukocytes/WBC count (up to 25%)^[Ref]

Hepatic

Very common (10% or more): Elevated liver enzymes (ALT and AST; up to 32%), increased ALT (up to 24%), increased AST (up to 23%)^[Ref]

In patients treated with this drug, elevated liver enzymes (ALT and AST) occurred in 32% of patients; Grade 3 and 4 elevated liver enzymes occurred in 2.3% and 0.4% of patients, respectively. The median time to onset was 43 days and the median time to resolution was 25 days.^[Ref]

Metabolic

Very common (10% or more): Decreased appetite (up to 35%), hypokalemia (up to 29%), hypomagnesemia (up to 29%), dehydration (up to 12%)^[Ref]

Musculoskeletal

Very common (10% or more): Musculoskeletal pain (includes arthralgia, back pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, noncardiac chest pain, pain in extremity, spinal pain; up to 34%)^[Ref]

Nervous system

Very common (10% or more): Headache (10%)

Common (1% to 10%): Peripheral neuropathy^[Ref]

Ocular

Very common (10% or more): Ocular toxicity (includes dry eye, eye pruritus, abnormal sensation in eye, eye discharge, blepharitis, trichiasis, conjunctival hemorrhage, vitreous floaters, blurred vision, corneal edema; up to 11%)^[Ref]

Other

Very common (10% or more): Fatigue (includes fatigue, asthenia; up to 33%), decreased potassium (up to 29%), increased alkaline phosphatase (up to 25%), decreased albumin (up to 23%), decreased magnesium (up to 23%), decreased weight (up to 21%), decreased sodium (up to 20%)

Common (1% to 10%): Edema^[Ref]

Psychiatric

Common (1% to 10%): Insomnia

Renal

Very common (10% or more): Increased creatinine (up to 52%)

Common (1% to 10%): Renal failure (includes acute kidney injury, decreased creatinine renal clearance, decreased GFR, renal failure, renal impairment), acute kidney injury^[Ref]

In patients treated with this drug, increased creatinine occurred in 52% of patients; Grade 3 and 4 increased creatinine occurred in 3.9% and 0.8% of patients, respectively. The median time to onset was 29 days and the median time to resolution was 29 days.^[Ref]

Respiratory

In patients treated with this drug at the recommended dosage of 160 mg once a day, ILD/pneumonitis occurred in 4.3% of patients including 0.8% Grade 3 events and 1.2% fatal events. The median time to onset was 55 days and the median time to resolution was 17 days; resolution occurred in 45% of patients.^[Ref]

Very common (10% or more): Dyspnea (includes dyspnea, exertional dyspnea; up to 19%), cough (includes cough, productive cough, upper airway cough syndrome; up to 17%), upper respiratory tract infection (includes nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tract infection; up to 16%), rhinorrhea (up to 13%)

Common (1% to 10%): Interstitial lung disease (includes interstitial lung disease [ILD], pneumonitis, respiratory failure), pneumonitis, pneumonia^[Ref]