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
Prevalence
KRASG12C inhibition
Efficacy
CodeBreaK 100
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CodeBreaK™ 100 logo

US Prescribing Information

CodeBreaK 100 was a single-arm, open-label, global, multicenter clinical trial with the Phase 2 portion evaluating LUMAKRAS in 126 patients with locally advanced or metastatic KRAS G12C–mutated NSCLC who progressed on prior therapy. Major efficacy outcomes in patients with ≥ 1 measurable lesion (BICR according to RECIST v1.1; n=124) were objective response rate (36% [95% CI: 28–45]; CR: 2%, PR: 35%), and duration of response (median: 10.0 months [range 1.3+, 11.1]; ≥ 6 months: 58% of patients observed beyond landmark time).1,2

Study design

Code Break logo : The first trial to demonstrate KRAS G12C as targetable in NSCLC1

The global CodeBreaK 100 study was a single-arm, open-label, multicenter clinical trial that enrolled patients who had progressed on prior therapy1,2

Phases one and two of CodeBreaK 100 clinical trial Phases one and two of CodeBreaK 100 clinical trial

Amgen's CodeBreaK clinical trial program is the first KRAS G12C–specific development program studied in the broadest number of countries and sites, with the most patients and longest follow-up3

*Consistent efficacy results were seen in patients with a KRAS G12C mutation, identified in either tissue or plasma specimens.5

†Across both Phase 1 and Phase 2 of the study, 2 subjects without baseline target lesions and 4 subjects without data for postbaseline percent changes are not shown.6

‡Safety follow-up occurred 30 (+7) days after the last dose of LUMAKRAS. Long-term follow-up occurred every 12 (±2) weeks for up to 3 years.2

§2 patients did not have measurable lesions at baseline and were ineligible for response assessment.6,7

CDx, companion diagnostic; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction.

Baseline characteristics

LUMAKRAS was specifically designed for patients with a KRAS G12C mutation1,**

Key baseline demographics and disease characteristics in the Phase 2 portion of the CodeBreaK 100 trial (N=126)1,††

Median age

64 (37–80 years)

Prior lines of systemic therapy

43% received 1 prior line of therapy
35% received 2 prior lines of therapy
23% received 3 prior lines of therapy

Sites of extrathoracic metastases

48% bone
21% brain
21% liver

Sex

50% female

Prior therapy received

91% received prior anti–PD-[L]1 immunotherapy
90% received prior platinum-based chemotherapy
81% received prior anti–PD-[L]1 + platinum-based chemotherapy

Smoking history

93% individuals who currently or previously smoked

Histology

99% non-squamous

**LUMAKRAS has only been studied in the KRAS G12C variant.1

††Phase 2 portion of CodeBreaK 100.2

Objective response rate

LUMAKRAS delivered an objective response rate of 36%1,2

Major efficacy outcomes: ORR and DOR1

In KRAS G12C–mutated locally advanced or metastatic NSCLC following prior therapy1

US Prescribing Information

LUMAKRAS® (sotorasib) objective response rate and disease control rate

Objective response rate

  • Consistent efficacy results were seen in patients with a KRAS G12C mutation identified in either tissue or plasma specimens5

+Symbol indicates censoring.

‡‡As determined by a BICR according to RECIST v1.1.1,4

§§Observed proportion of patients with duration of response beyond landmark time.1


BICR, blinded independent central review; CI, confidence interval; CR, complete response; DOR, duration of response; ORR, objective response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.

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.