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HOW WAS KRAZATI TESTED?

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Study design ↓

Heavily pretreated patient population ↓

First-to-market, accelerated approval for KRAZATI + cetuximab

Safety and efficacy were evaluated in KRYSTAL-1, a phase 1/2 single-arm, open-label expansion cohort study.​1,2

(N=94, who were evaluable by BICR according to RECIST v1.1)

Key inclusion criteria1

  • Locally advanced or metastatic CRC
  • Confirmed KRAS G12C mutation determined in tumor tissue
  • Phases 1 and 2: No available treatment with curative intent or patient refuses/is ineligible for standard of care 
  • Phase 2: Patients previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and a VEGF pathway inhibitor, if eligible

KRAZATI 600 mg BID1

  • Until disease progression or unacceptable toxicity
  • Phase 1 (n=32): Cetuximab administered weekly (400 mg/m2 loading dose, followed by 250 mg/m2 weekly) or biweekly (500 mg/m2)​1,2
  • Phase 2 (n=62): Cetuximab administered biweekly only1,2

Key study objectives2

  • Primary endpoint: Safety for phase 1 and ORR in phase 2
  • Secondary endpoints: Safety and DOR
  • Median follow-up time: 30 months for phase 1 and 10 months for phase 2

KRAZATI was studied in a heavily pretreated population1,2

Key baseline demographics KRYSTAL-1 study, chart

KRYSTAL-1 enrolled heavily pretreated patients with a median of 3 prior lines of therapy.​

  • 92% of patients had 2 or more prior lines of therapy​
  • 25% of patients in the KRYSTAL-1 trial had 4 or more prior lines of therapy​

Patients previously unable to receive EGFR inhibitors because of their KRAS G12C mutation now have the ability to target their advanced CRC with KRAZATI + cetuximab.

BICR=blinded independent central review; BID=twice-daily; CRC=colorectal cancer; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group Performance Status; ORR=objective response rate; RECIST=Response Evaluation Criteria in Solid Tumors; VEGF=vascular endothelial growth factor.

See the clinical data for KRAZATI  →

References:

  1. KRAZATI®. Prescribing information. Princeton, NJ. Mirati Therapeutics, Inc., a Bristol Myers Squibb company; 2024.
  2. Yaeger R, Uboha NV, Pelster MS, et al. Efficacy and safety of adagrasib plus cetuximab in patients with KRASG12C-mutated metastatic colorectal cancer. Cancer Discov. 2024;14(6):982-993. doi:10.1158/2159-8290.CD-24-0217

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Gastrointestinal Adverse Reactions

 

  • KRAZATI can cause severe gastrointestinal adverse reactions

  • Monitor and manage patients using supportive care, including antidiarrheals, antiemetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue KRAZATI based on severity

QTc Interval Prolongation

 

  • KRAZATI can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (eg, torsades de pointes) or sudden death

  • Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Avoid use of KRAZATI in patients with congenital long QT syndrome and in patients with concurrent QTc prolongation

  • Monitor ECGs and electrolytes, particularly potassium and magnesium, prior to starting KRAZATI, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are unable to avoid concomitant medications that are known to prolong the QT interval. Correct electrolyte abnormalities. Withhold, reduce the dose, or permanently discontinue KRAZATI, depending on severity

Hepatotoxicity

 

  • KRAZATI can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis

  • Monitor liver laboratory tests (AST, ALT, alkaline phosphatase, and total bilirubin) prior to the start of KRAZATI, and monthly for 3 months or as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue KRAZATI based on severity

Interstitial Lung Disease/Pneumonitis

 

  • KRAZATI can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal

  • Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever) during treatment with KRAZATI. Withhold KRAZATI in patients with suspected ILD/pneumonitis and permanently discontinue KRAZATI if no other potential causes of ILD/pneumonitis are identified

ADVERSE REACTIONS

 

  • Serious adverse reactions occurred in 30% of 94 patients who received adagrasib in combination with cetuximab. The most common adverse reactions in CRC patients (≥20%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, dizziness, cough, constipation, and peripheral neuropathy

DRUG INTERACTIONS

 

  • Strong CYP3A4 Inducers: Avoid concomitant use.

  • Strong CYP3A4 Inhibitors: Avoid concomitant use until adagrasib concentrations have reached steady state (after ~8 days).

  • Sensitive CYP3A4 Substrates: Avoid concomitant use with sensitive CYP3A4 substrates.

  • Sensitive CYP2C9 or CYP2D6 Substrates or P-gp Substrates: Avoid concomitant use with sensitive CYP2C9 or CYP2D6 substrates or P-gp substrates where minimal concentration changes may lead to serious adverse reactions.

  • Drugs That Prolong QT Interval: Avoid concomitant use with KRAZATI.

Please see Drug Interactions Section of the Full Prescribing Information for additional information.

USE IN SPECIFIC POPULATIONS

Females and Males of Reproductive Potential

 
  • Infertility: Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential

Lactation

 
  • Advise not to breastfeed

Please see Full Prescribing Information.

 

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© 2024 Mirati Therapeutics, Inc., a Bristol Myers Squibb company. KRAZATI® and the related logo are registered trademarks of Mirati Therapeutics, Inc.

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