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. ...Read More

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
Expanded Access Program
Safety
Dosing
Dosing
Dose modification
Coadministration
Testing
Why to test
How to test
Support & Resources
Amgen SupportPlus
Dispensing resources
Patient resources
HOME

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

EAP*

Global Expanded Access Program (EAP)*

The LUMAKRAS global EAP allowed compassionate use of LUMAKRAS for patients outside of clinical trials prior to local regulatory approvals who had exhausted other standard-of-care treatment. One study protocol* investigated data from the EAP to evaluate real-world safety and efficacy of LUMAKRAS in 92 patients from the USA (n=53), Israel (n=19), Brazil (n=19), and Taiwan (n=1) with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC. The primary endpoint of the protocol was safety. Treatment duration was included as a key secondary endpoint. rwPFS† was evaluated as an ad hoc endpoint.3,4

+Symbol indicates censoring.

*Data cutoff: June 24, 2022. Data were from NCT04667234 only (Amgen study 20190436).3

†rwPFS was estimated based on time from start of treatment to end of protocol sotorasib due to disease progression or death, any death before new anticancer therapy, or end of commercial LUMAKRAS, whichever occurred earlier.4

BICR, blinded independent central review; CI, confidence interval; CR, complete response; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; rwPFS, real-world progression-free survival.

Study design

Global EAP protocol* evaluated real-world safety and efficacy of LUMAKRAS (N=92)3,4

LUMAKRAS® (sotorasib) global study design
LUMAKRAS® (sotorasib) global study design

*Data cutoff: June 24, 2022. Data were from NCT04667234 only (Amgen study 20190436).3

OS, overall survival.

Baseline characteristics

Baseline demographics and clinical characteristics of patients receiving LUMAKRAS through a global EAP protocol* (N=92)4

At baseline, patients were heavily pretreated: 26% had ECOG PS 2 and 38% had a history of brain metastases4

Baseline characteristics of patients receiving LUMAKRAS® (sotorasib)
Baseline characteristics of patients receiving LUMAKRAS® (sotorasib)

*Data cutoff: June 24, 2022. Data were from NCT04667234 only (Amgen study 20190436).3

§Patients could be enrolled if contraindicated to standard-of-care therapies.4

PD-L1, programmed cell death ligand 1; VEGF, vascular endothelial growth factor.

Key safety

The safety profile of LUMAKRAS in the global EAP protocol* was consistent with that of the Phase 1/2 CodeBreaK 100 trial4

Treatment-related adverse events (TRAEs) (N=92)3

LUMAKRAS® (sotorasib) treatment-related AE
LUMAKRAS® (sotorasib) treatment-related AE
  • No suspected drug-induced liver injury cases by Hy’s law occurred3
  • One fatal TRAE was due to pneumonitis, with an onset of approximately 2.5 months after initiating LUMAKRAS treatment4

Adverse reactions (≥ 5%) (N=92)3

LUMAKRAS® (sotorasib) adverse reactions
LUMAKRAS® (sotorasib) adverse reactions

Important considerations3

  • The LUMAKRAS global EAP allowed compassionate use of LUMAKRAS for patients outside of clinical trials prior to local regulatory approvals who had exhausted other standard-of-care treatment
  • One study protocol* investigated data from the EAP to evaluate real-world safety and efficacy of LUMAKRAS in 92 patients from the USA (n=53), Israel (n=19), Brazil (n=19), and Taiwan (n=1) with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC
  • Key eligibility criteria included patients with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC, ECOG PS ≤ 2, and treated or stable, untreated brain metastases
  • The statistical reporting of safety and efficacy endpoints was descriptive with no formal statistical testing performed

*Data cutoff: June 24, 2022. Data were from NCT04667234 only (Amgen study 20190436).3

ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; ECOG PS, Eastern Cooperative Oncology Group performance status;
SAE, serious adverse event.

Treatment duration

Treatment duration in patients receiving LUMAKRAS through the global EAP protocol4,*

Treatment duration by ECOG PS (2 vs 0/1) (N=92)4

North America patients depth of response
North America patients depth of response
  • The median duration of treatment was 5.8 (95% CI: 2.3–11.7) months in patients with ECOG PS 0 and 6.2 (95% CI: 3.4–9.1) months in patients with ECOG PS 14
  • Of the 33% (30/92) of patients who switched to commercial LUMAKRAS, 25 initiated treatment within 1–2 days after the end of protocol sotorasib, 3 started 4, 5, and 17 days after protocol sotorasib, and 2 discontinued protocol sotorasib due to an AE and initiated commercial LUMAKRAS 34 and 99 days later4

Important considerations3

  • The LUMAKRAS global EAP allowed compassionate use of LUMAKRAS for patients outside of clinical trials prior to local regulatory approvals who had exhausted other standard-of-care treatment
  • One study protocol* investigated data from the EAP to evaluate real-world safety and efficacy of LUMAKRAS in 92 patients from the USA (n=53), Israel (n=19), Brazil (n=19), and Taiwan (n=1) with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC
  • Key eligibility criteria included patients with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC, ECOG PS ≤ 2, and treated or stable, untreated brain metastases
  • The statistical reporting of safety and efficacy endpoints was descriptive with no formal statistical testing performed
  • The study was not powered to assess efficacy in subgroups because it was not a prespecified study objective

*Data cutoff: June 24, 2022. Data were from NCT04667234 only (Amgen study 20190436).3

AE, adverse event.

Progression-free survival

Real-world progression-free survival (rwPFS) in patients receiving LUMAKRAS through the global EAP protocol4,*,†

Median rwPFS (N=92)4

rwPFS was generally consistent across patient subgroups4

Important considerations3

  • The LUMAKRAS global EAP allowed compassionate use of LUMAKRAS for patients outside of clinical trials prior to local regulatory approvals who had exhausted other standard-of-care treatment
  • One study protocol* investigated data from the EAP to evaluate real-world safety and efficacy of LUMAKRAS in 92 patients from the USA (n=53), Israel (n=19), Brazil (n=19), and Taiwan (n=1) with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC
  • Key eligibility criteria included patients with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC, ECOG PS ≤ 2, and treated or stable, untreated brain metastases
  • The statistical reporting of safety and efficacy endpoints was descriptive with no formal statistical testing performed
  • The study was not powered to assess efficacy in subgroups because it was not a prespecified study objective

*Data cutoff: June 24, 2022. Data were from NCT04667234 only (Amgen study 20190436).3

†rwPFS was estimated for Amgen study 20190436 (allowed for long-term follow-up) based on the time from the start of treatment to the end of protocol sotorasib due to disease progression or death, any death before new anticancer therapy, or end of commercial LUMAKRAS, whichever occurred earlier.4

‡Of note, a higher percentage of patients < 65 years of age (41.7%) had a best response of disease progression on last prior therapy compared to those ≥ 65 years (26.8%).4

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.