Lumakras Adverse Reactions

The following clinically significant adverse reactions are discussed in greater detail in other sections of the monograph: Hepatotoxicity [see Hepatotoxicity under Precautions]; Interstitial Lung Disease (ILD)/Pneumonitis [see Interstitial Lung Disease (ILD)/Pneumonitis under Precautions].
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 pooled safety population described in the PRECAUTIONS reflect exposure to LUMAKRAS as a single agent at 960 mg orally once daily in 357 patients with NSCLC and other solid tumors with KRAS G12C mutation enrolled in CodeBreaK 100, 28% were exposed for 6 months or longer and 3% were exposed for greater than one year.
Non-Small Cell Lung Cancer: metastatic NSCLC in CodeBreaK 100 [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Patients received LUMAKRAS 960 mg orally once daily until disease progression or unacceptable toxicity (n=204). Among patients who received LUMAKRAS, 39% were exposed for 6 months or longer and 3% were exposed for greater than one year.
The median age of patients who received LUMAKRAS was 66 years (range: 37 to 86); 55% female; 80% White, 15% Asian, and 3% Black.
Serious adverse reactions occurred in 50% of patients treated with LUMAKRAS. Serious adverse reactions in ≥2% of patients were pneumonia (8%), hepatotoxicity (3.4%), and diarrhea (2%). Fatal adverse reactions occurred in 3.4% of patients who received LUMAKRAS due to respiratory failure (0.8%), pneumonitis (0.4%), cardiac arrest (0.4%), cardiac failure (0.4%), gastric ulcer (0.4%), and pneumonia (0.4%).
Permanent discontinuation of LUMAKRAS due to an adverse reaction occurred in 9% of patients. Adverse reactions resulting in permanent discontinuation of LUMAKRAS in ≥2% of patients included hepatotoxicity (4.9%).
Dosage interruptions of LUMAKRAS due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥2% of patients were hepatotoxicity (11%), diarrhea (8%), musculoskeletal pain (3.9%), nausea (2.9%), and pneumonia (2.5%).
Dose reductions of LUMAKRAS due to an adverse reaction occurred in 5% of patients. Adverse reactions which required dose reductions in ≥2% of patients included increased ALT (2.9%) and increased AST (2.5%).
The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. The most common laboratory abnormalities (≥25%) were decreased lymphocytes, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium.
Table 4 summarizes the common adverse reactions observed in CodeBreaK 100. (See Table 4.)

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Table 5 summarizes the selected laboratory adverse reactions observed in CodeBreaK 100. (See Table 5.)

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