Adagrasib

Adagrasib is an irreversible inhibitor of KRAS G12C that covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state that prevents downstream signaling without affecting wild-type KRAS protein. Adagrasib inhibited tumor cell growth and viability in cells harboring KRAS G12C mutations and resulted in tumor regression in KRAS G12C-mutated tumor xenograft models with minimal off-target activity.

• KRAZATI is an inhibitor of the RAS GTPase family indicated for: Non-small cell lung cancer (NSCLC)* • As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. ( 1.1 ) Colorectal cancer (CRC)* • In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.ICD-10: C18.9, C34.90

• None. None.contraindicated

• Recommended dosage as a single agent for NSCLC and in combination with cetuximab for CRC: 600 mg orally twice daily. ( 2.2 ) • Swallow tablets whole with or without food. ( 2.2 ) 2.1 Patient Selection Non-Small Cell Lung Cancer Select patients for treatment of locally advanced or metastatic NSCLC with KRAZATI based on the presence of KRAS G12C mutation in plasma or tumor specimens [see Clinical Studies (14.1) ] . If no mutation is detected in a plasma specimen, test tumor tissue. Colorectal Cancer Select patients for treatment of locally advanced or metastatic CRC with KRAZATI based on the presence of KRAS G12C mutation in tumor specimens [see Clinical Studies (14.2) ] . Information on FDA-approved tests for the detection of a KRAS G12C mutation is available at: https://www.fda.gov/CompanionDiagnostics 2.2 Recommended Dosage The recommended dosage of KRAZATI as a single agent or in combination with cetuximab is 600 mg orally twice daily until disease progression or unacceptable toxicity. Refer to the cetuximab prescribing information for cetuximab dosage information [see Clinical Studies (14.2) ] . Take KRAZATI at the same time every day with or without food [see Clinical Pharmacology (12.3) ]. Swallow tablets whole. Do not chew, crush or split tablets. If vomiting occurs after taking KRAZATI, do not take an additional dose. Resume dosing at the next scheduled time. If a dose is inadvertently missed, it should be skipped if greater than 4 hours have elapsed from the expected dosing time. Resume dosing at the next scheduled time.

• Gastrointestinal Adverse Reactions : Monitor patients for diarrhea, nausea and vomiting and provide supportive care as needed. Withhold, reduce the dose or permanently discontinue based on severity. ( 2.3 , 5.1 ) • QTc Interval Prolongation: Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Monitor ECG and electrolytes particularly potassium and magnesium, in patients at risk, and in patients taking medications known to prolong the QT interval. Correct electrolyte abnormalities. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.3 , 5.2 ) • Hepatotoxicity: Monitor liver laboratory tests prior to the start of KRAZATI and monthly for 3 months after and as clinically indicated. Reduce the dose, withhold, or permanently discontinue based on severity. ( 2.3 , 5.3 ) • Interstitial Lung Disease (ILD) / Pneumonitis: Monitor for new or worsening respiratory symptoms. Withhold KRAZATI for suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ( 2.3 , 5.4 ) 5.1 Gastrointestinal Adverse Reactions KRAZATI can cause severe gastrointestinal adverse reactions. In the pooled safety population [see Adverse Reactions (6.1) ] , who received single-agent KRAZATI, serious gastrointestinal adverse reactions observed were gastrointestinal bleeding in 3.8% including 0.8% Grade 3 or 4, gastrointestinal obstruction in 1.6% including 1.4% Grade 3 or 4, colitis in 0.5% including 0.3% Grade 3, ileus in 0.5%, and stenosis in 0.3%.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.1) ] • QTc Interval Prolongation [see Warnings and Precautions (5.2) ] • Hepatotoxicity [see Warnings and Precautions (5.3) ] • Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.4) ] • Single agent use in NCSLC: The most common adverse reactions (≥ 25%) were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, and decreased appetite. The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased hemoglobin, increased alanine aminotransferase, increased aspartate aminotransferase, hypokalemia, hyponatremia, increased lipase, decreased leukocytes, decreased neutrophils and increased alkaline phosphatase. ( 6.1 ) • In combination with cetuximab in CRC: The most common adverse reactions (≥ 25%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, and cough. The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased potassium, decreased magnesium, decreased hemoglobin, increased aspartate aminotransferase, increased lipase, decreased albumin, and increased alanine aminotransferase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no available data on the use of KRAZATI in pregnant women. In animal reproduction studies, oral administration of adagrasib to pregnant rats and rabbits during the period of organogenesis did not cause adverse development effects or embryo-fetal lethality at exposures below the human exposure at the recommended dose of 600 mg twice daily (see Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In a rat embryo-fetal development study, once daily oral administration of adagrasib to pregnant rats during the period of organogenesis resulted in maternal toxicity (reduced body weight and food intake, and adverse clinical signs leading to moribund condition and early termination) and lower fetal body weight at 270 mg/kg dose level (approximately 2 times the recommended dose of 600 mg twice daily based on body surface area [BSA]). Adagrasib induced skeletal malformations, such as bent limbs, and skeletal variations, such as bent scapula, wavy ribs, and supernumerary short cervical ribs at 270 mg/kg, which were secondary to maternal toxicity and reduced fetal body weight.

Metabolism

The pharmacokinetics of adagrasib were studied in healthy subjects and in patients with KRAS G12C-mutated NSCLC or CRC. Adagrasib pharmacokinetic data are presented as mean (percent coefficient of variation) unless otherwise specified.

• Dec 12, 2022NDANDA216340Bristol

1. 1Death28028%
2. 2Diarrhoea12513%
3. 3Hospitalisation10911%
4. 4Nausea959.5%
5. 5Vomiting858.5%
6. 6Off Label Use787.8%
7. 7Asthenia646.4%
8. 8Fatigue535.3%
9. 9Decreased Appetite434.3%
10. 10Dehydration414.1%
11. 11Acute Kidney Injury353.5%
12. 12Dyspnoea343.4%
13. 13Renal Failure282.8%
14. 14Dizziness272.7%
15. 15Weight Decreased242.4%

The 10 most recently updated of 39 ClinicalTrials.gov registrations naming Adagrasib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• ASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer
  Not yet recruiting · Early phase 1 · Interventional · 100 enrolled · M.D. Anderson Cancer Center
  NCT07318389updated 2026-06-11
• Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7
  Recruiting · Phase 2 · Phase 3 · Interventional · 626 enrolled · Mirati Therapeutics Inc.
  NCT04613596updated 2026-06-08
• KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors
  Recruiting · Phase 1 · Interventional · 300 enrolled · Kura Oncology, Inc.
  NCT06026410updated 2026-06-08
• A Study of BMS-986488 as Monotherapy and Combination Therapy in Participants With Advanced Malignant Tumors
  Recruiting · Phase 1 · Interventional · 437 enrolled · Bristol-Myers Squibb
  NCT06764771updated 2026-06-03
• A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)
  Recruiting · Phase 3 · Interventional · 630 enrolled · Mirati Therapeutics Inc.
  NCT06875310updated 2026-06-02
• A Solid Tumor Study for Long Term Treatment of Cancer Patients Who Participated in Adagrasib Studies
  Recruiting · Phase 2 · Interventional · 170 enrolled · Mirati Therapeutics Inc.
  NCT07415031updated 2026-05-15
• Adagrasib in Patients With KRASG12C-mutant NSCLC Who Are Elderly or Have Poor Performance Status
  Active not recruiting · Phase 2 · Interventional · 68 enrolled · ETOP IBCSG Partners Foundation
  NCT05673187updated 2026-04-27
• Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)
  Active not recruiting · Phase 3 · Interventional · 461 enrolled · Mirati Therapeutics Inc.
  NCT04793958updated 2026-04-27
• CIMAvax-EGF With KRAS G12C Inhibitor for the Treatment of Advanced, KRAS G12C Mutated Non Small Cell Lung Cancer
  Not yet recruiting · Phase 2 · Interventional · 29 enrolled · Roswell Park Cancer Institute
  NCT07543172updated 2026-04-21
• A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer
  Active not recruiting · Phase 3 · Interventional · 338 enrolled · Hoffmann-La Roche
  NCT06497556updated 2026-04-20

Frequently asked questions

How does Adagrasib work?

Adagrasib is an irreversible inhibitor of KRAS G12C that covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state that prevents downstream signaling without affecting wild-type KRAS protein. Adagrasib inhibited tumor cell growth and viability in cells harboring KRAS G12C mutations and resulted in tumor regression in KRAS G12C-mutated tumor xenograft models with minimal off-target activity.

What is Adagrasib used for?

According to FDA labeling, Adagrasib carries indications including: KRAZATI is an inhibitor of the RAS GTPase family indicated for: Non-small cell lung cancer (NSCLC)* • As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. ( 1.1 ) Colorectal cancer (CRC)* • In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Adagrasib?

Adagrasib is classified as Other antineoplastic agents.

What are the brand names for Adagrasib?

Adagrasib is marketed under brand names including Krazati.

What are the contraindications for Adagrasib?

Adagrasib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.