INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS • loo-ma-krass
SOTORASIB • soh-toh-rass-ib
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Adverse reactions

LUMAKRAS® (sotorasib) safety and tolerability were evaluated in 204 NSCLC patients1

US Prescribing Information

The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough in CodeBreaK 100 (N=204)1
Adverse reactions (≥ 10%) of patients with KRAS G12C–mutated NSCLC who received LUMAKRAS® (sotorasib) in CodeBreaK 100 (N=204)1,*
All Grades (%) Grades 3 to 4 (%)
Gastrointestinal disorders
Diarrhea 42 5
Nausea 26 1
Vomiting 17 1.5
Constipation 16 0.5
Abdominal pain† 15 1
Hepatobiliary disorders
Hepatotoxicity‡ 25 12
Respiratory, thoracic, and mediastinal disorders
Cough§ 20 1.5
Dyspnea** 16 2.9
Musculoskeletal and connective tissue disorders
Musculoskeletal pain†† 35 8
Arthralgia 12 1
General disorders and administration site conditions
Fatigue‡‡ 26 2
Edema§§ 15 0
Metabolism and nutrition disorders
Decreased appetite 13 1
Infections and infestations
Pneumonia*** 12 7
Skin and subcutaneous tissue disorders
Rash††† 12 0

*Grading defined by NCI CTCAE version 5.0.

†Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal pain lower.1

‡Hepatotoxicity includes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, drug-induced liver injury, hepatitis, hepatotoxicity, liver function test increased, and transaminases increased.1

§Cough includes cough, productive cough, and upper-airway cough syndrome.1

**Dyspnea includes dyspnea and dyspnea exertional.1

††Musculoskeletal pain includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and pain in extremity.1

‡‡Fatigue includes fatigue and asthenia.1

§§Edema includes generalized edema, localized edema, edema, edema peripheral, periorbital edema, and testicular edema.1

***Pneumonia includes pneumonia, pneumonia aspiration, pneumonia bacterial, and pneumonia staphylococcal.1

†††Rash includes dermatitis, dermatitis acneiform, rash, rash-maculopapular, and rash pustular.1


Use of anti-emetic and anti-diarrheal medications in CodeBreaK 100:2

  • 26% of patients received an anti-emetic
  • 32% of patients received an anti-diarrheal
3.4%had a grade 5 AR<span id="supr">1</span>

Grade 5 adverse reactions occurred in 3.4% of patients who received LUMAKRAS® (sotorasib) 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%)

9%discontinued LUMAKRAS<span id="supr">®</span> (sotorasib) due to AR<span id="supr">1</span>

Adverse reactions resulting in permanent discontinuation of LUMAKRAS® (sotorasib) in ≥ 2% of patients included hepatotoxicity (4.9%)

5%had a dose reduction<span id="supr">1</span>

5% of patients experienced a dose reduction due to an adverse reaction

34%had a dosage interruption<span id="supr">1</span >

34% of patients experienced a dosage interruption due to an adverse reaction

USPI monitoring and dose modification requirements for warnings and precautions1
Warnings and precautions Monitoring and dose modification Relevant clinical data from pooled safety population (n=549)
Hepatotoxicity
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS® (sotorasib), every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevation
  • Withhold, reduce the dose, or permanently discontinue LUMAKRAS® (sotorasib) based on the severity of adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity. Please reference the Dose Modification section for detailed guidance
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® (sotorasib) 960 mg, 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 NSCLC patients who received single agent LUMAKRAS® (sotorasib) 960 mg, 17% of patients who received LUMAKRAS® (sotorasib) had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST), of which 9% were Grade ≥ 3
  • The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4–42)
  • Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS® (sotorasib). LUMAKRAS® (sotorasib) was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3)
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® (sotorasib) 960 mg, a total of 40% of patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® (sotorasib) had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® (sotorasib) more than 3 months after the last dose of immunotherapy and in 17% of those who never received immunotherapy
  • Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS® (sotorasib), with or without corticosteroid treatment
Interstitial Lung Disease (ILD)/Pneumonitis
  • Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever)
  • Immediately withhold LUMAKRAS® (sotorasib) in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS® (sotorasib) if no other potential causes of ILD/pneumonitis are identified
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® (sotorasib) 960 mg, ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal
  • The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1–36.7)
  • LUMAKRAS® (sotorasib) was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS® (sotorasib)-treated patients
Other considerations1
Category Considerations
No QTc prolongation

Per the USPI cardiac electrophysiology section in pharmacodynamics, at the approved recommended dosage, LUMAKRAS® (sotorasib) does not cause large mean increases in the QTc interval (> 20 msec)

The LUMAKRAS® (sotorasib) USPI does not contain any requirements to monitor ECGs and electrolytes
No gastrointestinal warnings and precautions

At the approved recommended dosage, LUMAKRAS® (sotorasib) USPI does not include a warnings and precautions section on severe gastrointestinal adverse reactions

The most common adverse reactions (≥ 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough

AR, adverse reaction; ECG, electrocardiogram; KRAS, Kirsten rat sarcoma viral oncogene homolog; NCI CTCAE, National Cancer Institute Common Terminology
Criteria for Adverse Events; NSCLC, non-small cell lung cancer; QTc, QT corrected for heart rate; USPI, United States Prescribing Information.

Select laboratory abnormalities (≥ 20%) that worsened from baseline in patients with KRAS G12C–mutated NSCLC who received LUMAKRAS® (sotorasib) in CodeBreaK 100 (N=204*)1
Grades 1 to 4 (%) Grades 3 to 4 (%)
Chemistry
Increased aspartate aminotransferase 39 9
Increased alanine aminotransferase 38 11
Decreased calcium 35 0
Increased alkaline phosphatase 33 2.5
Increased urine protein 29 3.9
Decreased sodium 28 1
Decreased albumin 22 0.5
Hematology
Decreased lymphocytes 48 2
Decreased hemoglobin 43 0.5
Increased activated partial thromboplastin time 23 1.5
  • 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 sodium1

*N=number of patients who had at least one on-study assessment for the parameter of interest.1

Are you looking for information on patient characteristics
from the pivotal CodeBreaK 100 Phase 2 trial?

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
  • Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
  • Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
  • Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100 ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
  • Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most common adverse reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Please see full LUMAKRAS Prescribing Information.

References: 1. The Galien Foundation. https://www.prnewswire.com/news-releases/the-galien-foundation-honors-2022-prix-galien-award-recipients-301662219.html. Accessed December 6, 2022. 2. LUMAKRAS® (sotorasib) prescribing information, Amgen. 3. Canon J, et al. Nature. 2019;575(7781):217-223. 4. Data on file, Amgen; [Most prescribed chart audit]. 5. Data on file, Amgen; [Unique patients]. 6. Data on file, Amgen; [Unique prescribers]. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer v.1.2024. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed December 21, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. 8. Sotorasib CSR. Amgen; 2021. 9. The Galien Foundation. https://www.galienfoundation.org/what-you-must-know. Accessed December 6, 2022. 10. The Galien Foundation. https://candidates.prix-galien-usa.com/submissions/eligibility. Accessed December 1, 2022.

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg 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 NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (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. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS® can cause ILD/pneumonitis that can be fatal.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7 weeks). LUMAKRAS® was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS®-treated patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS® in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS® if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug Interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS®.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS® 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Please see full LUMAKRAS® Prescribing Information.

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg 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 NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (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. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS® can cause ILD/pneumonitis that can be fatal.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7 weeks). LUMAKRAS® was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS®-treated patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS® in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS® if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug Interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS®.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS® 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Please see full LUMAKRAS® Prescribing Information.

Important Safety Information

Hepatotoxicity

  • LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
  • Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
  • Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
  • Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Important Safety Information

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg 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 NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (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. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg 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 NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/ increased aspartate aminotransferase (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. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.