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
About KRAS G12C
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CodeBreaK 100
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Adverse reactions

LUMAKRAS 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 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, 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, 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, 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 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 due to adverse reactions<span id="supr">1</span>

Adverse reactions resulting in permanent discontinuation of LUMAKRAS 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
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 elevation
  • Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction. Please reference the Dose Modification section for detailed guidance
  • Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3) of patients
  • 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
  • The median time to first onset of increased ALT/AST was 9 weeks (range: 0.3–42)
  • Increased ALT/AST leading to dose interruption or reduction occurred in 7% of patients. LUMAKRAS was discontinued due to increased ALT/AST in 2% of patients
  • In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity
Interstitial Lung Disease (ILD)/Pneumonitis
  • Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, 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
  • 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
  • The median time to first onset for ILD/pneumonitis was 2 weeks (range: 2–18 weeks)
  • LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients
Other considerations1
Category Considerations
No QTc prolongation

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

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

At the approved recommended dosage, LUMAKRAS 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

ALT, alanine transaminase; AR, adverse reaction; AST, aspartate transaminase; 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 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 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.