Krazati (adagrasib)

Mirati Therapeutics announced on December 12, 2022 that the US Food and Drug Administration (FDA) had accelerated the approval of Krazati (adagrasib) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with KRAS G12C mutation, who had previously received at least one systemic treatment.

Krazati (adagrasib)_ Hong Kong Jimin Pharmaceutical

【 indications of Krazati (adagrasib) 】
It is suitable for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with G12C- mutation in adult KRAS patients, which has been confirmed by FDA-approved tests and received at least one systemic treatment before.
The indication was approved according to accelerated approval based on objective remission rate (ORR) and remission duration (DOR). The continued approval of this indication may depend on the verification and description of clinical benefits in confirmatory trials.

[Recommended dosage and administration method of Krazati(adagrasib)]
First, patient selection
According to the existence of KRAS G12C mutation in plasma or tumor samples, patients with locally advanced or metastatic NSCLC were selected to be treated with Krazati. If no mutation is detected in the plasma sample, the tumor tissue is detected.
Second, the recommended dose
The recommended dose of Krazati is 600mg, taken orally twice a day until the disease worsens or unacceptable toxicity appears. Take Krazati at the same time every day with or without meals. Swallow it whole. Do not chew, crush or split the tablets. If you vomit after taking Krazati, don’t take any extra dose. Resume administration at the next scheduled time. If a dose is inadvertently missed and more than 4 hours have passed since the expected administration time, the dose should be skipped. Resume administration at the next scheduled time.

[Warning and Precautions of Krazati(adagrasib)]
First, gastrointestinal adverse reactions
Krazati can cause serious gastrointestinal adverse reactions. According to the needs, patients should be monitored and managed with supportive care, including antidiarrheal drugs, antiemetic drugs or rehydration. According to the severity, suspend, reduce the dose or permanently stop Krazati.
Second, QTc interval prolongation
Krazati can prolong QTc interval, thus increasing the risk of ventricular tachycardia (such as torsade de pointes) or sudden death. Krazati leads to an increase in the concentration dependence of QTc interval, so it is necessary to avoid using Krazati together with other drugs that are known to prolong QTc interval. Patients with congenital long QT syndrome and QTc prolongation should avoid using Krazati. Electrocardiogram and electrolyte were monitored before starting the use of Krazati, during the concomitant medication, and when patients with congestive heart failure, bradyarrhythmia, electrolyte abnormality and patients who could not avoid concomitant medication known to prolong QT interval showed clinical indications. According to the severity, suspend, reduce the dose or permanently stop Krazati.
Iii. Hepatotoxicity
Krazati can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Before starting to take Krazati, the liver laboratory tests (AST, ALT, alkaline phosphatase and total bilirubin) were monitored once a month for 3 months, or according to clinical instructions, and patients with elevated transaminase were examined more frequently. According to the severity, reduce the dose, suspend or permanently stop Krazati.
Iv. interstitial lung disease/pneumonia
Krazati can cause fatal interstitial lung disease (ILD)/ pneumonia. During the treatment with Krazati, monitor whether the patients have new or worsening respiratory symptoms of ILD/ pneumonia (such as dyspnea, cough and fever). Stop Krazati in patients with suspected ILD/ pneumonia, and stop Krazati permanently if no other potential causes of ILD/ pneumonia are found.

[Adverse reaction of Krazati (adagrasib)]
The most common adverse reactions (≥25%) are nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal dysfunction, edema, dyspnea and loss of appetite.