Sotorasib

Sotorasib is an inhibitor of KRAS G12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRAS G12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS.

• LUMAKRAS is an inhibitor of the RAS GTPase family indicated for: KRAS G12C-mutated Locally Advanced or Metastatic 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 ) This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR).ICD-10: C34.90

• None. None.contraindicated

Recommended dosage as a single agent for NSCLC and in combination with panitumumab for mCRC: 960 mg orally once daily. ( 2.2 ) Swallow tablets whole with or without food. ( 2.2 ) 2.1 Patient Selection KRAS G12C-mutated Locally Advanced or Metastatic NSCLC Select patients for treatment of locally advanced or metastatic NSCLC with LUMAKRAS based on the presence of KRAS G12C mutation in tumor or plasma specimens. If no mutation is detected in a plasma specimen, test tumor tissue [see Clinical Studies (14.1) ]. KRAS G12C-mutated mCRC Select patients for treatment of mCRC 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 KRAS G12C mutations is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage and Administration LUMAKRAS as a Single Agent for KRAS G12C-mutated Locally Advanced or Metastatic NSCLC The recommended dosage of LUMAKRAS is 960 mg (three 320 mg tablets or four 240 mg tablets or eight 120 mg tablets) orally once daily until disease progression or unacceptable toxicity. LUMAKRAS in Combination with Panitumumab for KRAS G12C-mutated mCRC The recommended dosage of LUMAKRAS is 960 mg (three 320 mg tablets or four 240 mg tablets or eight 120 mg tablets) orally once daily in combination with panitumumab until disease progression or unacceptable toxicity. Administer the first dose of LUMAKRAS prior to first panitumumab infusion. Refer to the panitumumab full prescribing information for recommended panitumumab dosage information.

Hepatotoxicity: Monitor liver function tests every 3 weeks for the first 3 months of treatment then once monthly as clinically indicated. Consider administering systemic corticosteroids and withhold, reduce the dose, or permanently discontinue LUMAKRAS based on the severity. ( 2.3 , 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms. Immediately withhold LUMAKRAS for suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ( 2.3 , 5.2 ) 5.1 Hepatotoxicity LUMAKRAS can cause hepatotoxicity and increased alanine aminotransferase (ALT) or increased aspartate aminotransferase (AST) which may lead to drug-induced liver injury and hepatitis. In the pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg [see Adverse Reactions (6.1) ] , hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids. In this pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg, 17% of patients who received LUMAKRAS had increased ALT/increased AST; of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS. LUMAKRAS was permanently discontinued due to increased ALT/AST in 2.7% of patients.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2) ] Single agent in NSCLC: 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. ( 6.1 ) In combination with panitumumab in CRC: The most common adverse reactions (≥ 20%) in clinical trials of LUMAKRAS in combination with panitumumab are rash, dry skin, diarrhea, stomatitis, fatigue and musculoskeletal pain. The most common Grade 3 or 4 laboratory abnormalities in ≥ 2 patients (4.3%) were decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no available data on LUMAKRAS use in pregnant women. In rat and rabbit embryo-fetal development studies, oral sotorasib did not cause adverse developmental effects or embryo-lethality at exposures up to 4.6 times the human exposure at the 960 mg clinical dose (see Data ) . Refer to the Full Prescribing Information of panitumumab for pregnancy risk information and contraception recommendations when LUMAKRAS is administered in combination with panitumumab. 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 sotorasib to pregnant rats during the period of organogenesis resulted in maternal toxicity at the 540 mg/kg dose level (approximately 4.6 times the human exposure based on area under the curve (AUC) at the clinical dose of 960 mg). Sotorasib did not cause adverse developmental effects and did not affect embryo-fetal survival at doses up to 540 mg/kg.

Metabolism

The pharmacokinetics of sotorasib have been characterized in healthy subjects and in patients with KRAS G12C -mutated solid tumors, including NSCLC. Sotorasib exhibited non-linear, time-dependent, pharmacokinetics over the dose range of 180 mg to 960 mg (0.19 to 1 time the approved recommended dosage) once daily with similar systemic exposure (i.e., AUC 0-24h and C max ) across doses at steady state.

• May 28, 2021NDANDA214665Amgen Inc

1. 1Non-small Cell Lung Cancer49916%
2. 2Death34811%
3. 3Disease Progression32911%
4. 4Diarrhoea3049.7%
5. 5Off Label Use2166.9%
6. 6Nausea1053.4%
7. 7Non-small Cell Lung Cancer Metastatic983.1%
8. 8Fatigue973.1%
9. 9Hepatotoxicity963.1%
10. 10Hepatic Function Abnormal892.9%
11. 11Alanine Aminotransferase Increased792.5%
12. 12Aspartate Aminotransferase Increased792.5%
13. 13Drug Ineffective672.1%
14. 14Lung Neoplasm Malignant662.1%
15. 15Decreased Appetite632.0%

The 10 most recently updated of 72 ClinicalTrials.gov registrations naming Sotorasib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
  Recruiting · Phase 2 · Interventional · 2,900 enrolled · National Cancer Institute (NCI)
  NCT05564377updated 2026-06-12
• 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
• Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal Cancer With KRAS p.G12C Mutation
  Recruiting · Phase 3 · Interventional · 450 enrolled · Amgen
  NCT06252649updated 2026-06-10
• A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
  Recruiting · Phase 3 · Interventional · 750 enrolled · Amgen
  NCT05920356updated 2026-06-04
• Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).
  Active not recruiting · Phase 1 · Interventional · 49 enrolled · Amgen
  NCT06333951updated 2026-05-28
• A Study of Sotorasib in People With Brain Tumors
  Recruiting · Phase 1 · Interventional · 16 enrolled · Memorial Sloan Kettering Cancer Center
  NCT06807619updated 2026-05-22
• A Rollover Study Evaluating Sotorasib With or Without Panitumumab in Participants With KRAS p.G12C Mutation
  Recruiting · Phase 2 · Interventional · 14 enrolled · Amgen
  NCT07172919updated 2026-05-14
• Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation
  Recruiting · Phase 1 · Phase 2 · Interventional · 37 enrolled · National Cancer Institute (NCI)
  NCT07012031updated 2026-05-13
• Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)
  Active not recruiting · Phase 2 · Interventional · 105 enrolled · National Cancer Institute (NCI)
  NCT05638295updated 2026-05-13
• A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation
  Recruiting · Phase 1 · Interventional · 104 enrolled · Bayer
  NCT06659341updated 2026-05-12

Frequently asked questions

How does Sotorasib work?

Sotorasib is an inhibitor of KRAS G12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRAS G12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS.

What is Sotorasib used for?

According to FDA labeling, Sotorasib carries indications including: LUMAKRAS is an inhibitor of the RAS GTPase family indicated for: KRAS G12C-mutated Locally Advanced or Metastatic 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 ) This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sotorasib?

Sotorasib is classified as Other antineoplastic agents.

What are the brand names for Sotorasib?

Sotorasib is marketed under brand names including Lumakras.

What are the contraindications for Sotorasib?

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