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).
NSCLC
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Adverse reactions Monitoring Pooled safety analysis

Adverse reactions and safety considerations

LUMAKRAS® (sotorasib) safety and tolerability were evaluated in CodeBreaK 100 (N=204) KRAS G12C–mutated NSCLC patients1

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,*
Adverse reactions table for patients with KRAS G12C-mutated NSCLC who received LUMAKRAS in CodeBreaK 100 Adverse reactions table for patients with KRAS G12C-mutated NSCLC who received LUMAKRAS in CodeBreaK 100

*Grading defined by NCI CTCAE version 5.0.1

†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

Safety considerations1

3.4%
had a Grade 5 AR

Grade 5 adverse reactions occurred in 3.4% of patients 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 AR

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

5%
had a dose reduction due to AR
34%
had a dosage interruption due to AR
Use of antiemetic and antidiarrheal medications in CodeBreaK 100:2

  • 26% of patients received an antiemetic

  • 32% of patients received an antidiarrheal

Select laboratory abnormalities (≥ 20%) that worsened from baseline (N=204)1

    • 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.

    Expand to see laboratory abnormalities1
    laboratory abnormalities laboratory abnormalities

    AR, adverse reaction; KRAS, Kirsten rat sarcoma viral oncogene homolog; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer.

    Monitoring

    USPI monitoring and dose modification requirements for warnings and precautions1

    Hepatotoxicity

    Monitor liver function tests (ALT, AST, alkaline phosphate, 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 trasaminase and/or bilirubin elevation

    • Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction

    • Consider administering systemic corticosteroids for the management of hepatotoxicity

    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

      For more information on adverse event monitoring and management, please see the Prescribing Information.

      ALT, alanine transaminase; AST, aspartate transaminase; ILD, interstitial lung disease; USPI, United State Prescribing Information.

      Pooled safety analysis

      The LUMAKRAS® pooled safety analysis, across 549 patients with KRAS G12C–mutated NSCLC, is the largest safety analysis of any KRAS G12C inhibitor3

      LUMAKRAS® demonstrated consistent safety across multiple clinical trials, including CodeBreaK 100, 101, 200, and 1053

       

        • The pooled safety population reflects exposure to LUMAKRAS® as a single agent at 960 mg orally once daily until disease progression or unacceptable toxicity in 549 patients with NSCLC with the KRAS G12C mutation.

           

        Hepatotoxicity1,*

        In the pooled safety analysis, regardless of time from prior immunotherapy, 94% of hepatotoxicity treatment-emergent adverse events (TEAEs) improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.

         

          • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST, which may lead to drug-induced liver injury and hepatitis

            • Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3)

          • Median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4–42)

          Hepatotoxicity TEAEs in the pooled safety population (n=549)1,4
          Table showing hepatotoxicity events in the pooled safety population Table showing hepatotoxicity events in the pooled safety population

           

            • Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.1

               

            ILD/pneumonitis1

            ILD/pneumonitis TEAEs occurred in 2.2% of patients who received single agent LUMAKRAS® 960 mg

              • 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 weeks)

              • LUMAKRAS® was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS®-treated patients

              Gastrointestinal3

              Gastrointestinal treatment-related adverse events (TRAEs) were generally managed with dose interruptions and supportive care, with low rates of discontinuation associated with these reactions†,‡,§,**

              Percentage of patients experiencing Grade ≥ 1 diarrhea TRAEs (N=549)
              Table showing diarrhea treatment-related adverse event grades Table showing diarrhea treatment-related adverse event grades

              • Dose interruption and dose reduction of LUMAKRAS® resulted in resolution of > 90% of diarrhea TRAEs; median time to resolution were 18 days and 22 days, respectively.

                 

              Percentage of patients experiencing Grade ≥ 1 nausea or vomiting TRAEs (N=549)
              Table showing percentages of nausea and vomiting treatment-related adverse event grades Table showing percentages of nausea and vomiting treatment-related adverse event grades

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

              †35.7% had a dose interruption due to diarrhea TRAEs; 16.4% had a dose reduction due to diarrhea TRAEs; 1.8% discontinued due to diarrhea TRAEs.3

              ‡37.5% of patients received anti-emetics for nausea; 44.1% received them for vomiting.3

              §20% of patients’ nausea led to dose interruption, 1.3% led to dose reduction, and no patients discontinued due to nausea.3

              **17.6% of patients’ vomiting led to dose interruption, 2.9% led to dose reduction, and 2.9% led to discontinuation.3

              At the approved recommended dosage, LUMAKRAS® USPI does not include a Warnings and Precautions section on severe gastrointestinal adverse reactions

              ALT, alanine transaminase; AST, aspartate transaminase; I-O, immuno-oncology; ILD, interstitial lung disease; KRAS, Kirsten rat sarcoma viral oncogene homolog.

              Learn more about dosing

              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.

              • References: 1. LUMAKRAS® (sotorasib) prescribing information, Amgen. 2. Data on file, Amgen; [Anti-Emetics, Anti-Diarrheals]. 3. Skoulidis F, et al. Nat Rev Cancer. 2019;19:495-509. 4. Data on file, Amgen; [Pooled Safety Analysis].