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).

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 [1.3+, 11.1]; ≥ 6 months: 58% of patients observed beyond landmark time).1,2

Objective response rate

LUMAKRAS™ delivered an objective response rate of 36% and a disease control rate of 81%1,2

Major efficacy outcomes: ORR and DOR1
Additional key efficacy outcomes: DCR, OS, and PFS2

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

US Prescribing Information:
Data cutoff: September 1, 20203

Objective response rate

Objective response rate

  • Consistent efficacy results were seen in patients with KRAS G12C mutation identified in either tissue or plasma specimens4

 

Additional follow-up:
Data cutoff: March 15, 2021

Objective response rate

Objective response rate

Consistent efficacy was seen across prespecified subgroups7

Efficacy in subgroups by baseline characteristics7,§




  • These results represent prespecified subgroup analyses of the CodeBreaK 100 study; however, these analyses were not study objectives and the study was therefore not powered or adjusted for multiplicity to assess efficacy in these subgroups

Important considerations

  • CodeBreaK 100 was a Phase 2, single-arm, open-label, global, multicenter clinical trial1,2
  • LUMAKRAS™ is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR)1
  • Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)1

+symbol indicates censoring.

*As determined by a BICR according to RECIST v1.1.1

Disease control rate = CR + PR + stable disease.

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

§The sample size (N) for three subgroups are smaller compared to the sample size for the overall population evaluated (N=124). The sample size for “No prior anti–PD-1/PD-L1 received,” “Prior platinum-based chemo but no anti–PD-1/PD-L1,” and “Prior anti–PD-1/PD-L1 but no platinum-based chemo” are 11, 11, and 13, respectively.7

BICR, blinded independent central review; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; KRAS, Kirsten rat sarcoma viral oncogene homolog; mOS, median overall survival; NE, not evaluable; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria In Solid Tumors.

Depth of response

LUMAKRAS™ shrank tumors and/or suppressed tumor growth in 81% of patients5

Best tumor change from baseline (n=121)5,**

Tumor response Tumor response
  • Disease control rate observed in 81% (100/124) of patients5
  • Complete response observed in 3% (4/124) of patients5

Phase 2 data cutoff date: March 15, 2021.5
Percent change from baseline in sum of diameters only considers tumor assessments prior to and including the first assessment where the timepoint response is PD and prior to start of next anticancer therapy.5
**Data were excluded from 3 patients: 2 who had missing scans and 1 who had no measurement in target lesions and had PD in nontarget lesions (PD as the best overall response).5

BOR, best overall response; PD, progressive disease; SD, stable disease.

Overall survival

Overall survival in patients receiving LUMAKRAS™ post I-O and/or platinum-based chemotherapy5

Overall survival

Overall survival Overall survival
  • The median follow-up time was 15.3 (1.1–18.4+) months5

Important considerations

  • CodeBreaK 100 was a Phase 2, single-arm, open-label, global, multicenter clinical trial1,2
  • LUMAKRAS™ is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR)1
  • Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)1
  • Single-arm trials do not adequately characterize time-to-event endpoints such as overall survival. Thus, the OS data from CodeBreaK 100 cannot be directly interpreted as a survival benefit

Phase 2 data cutoff date: March 15, 2021.5

+ indicates that the value includes data that were censored at data cutoff.5

Censor indicated by vertical bar. Death is an event.5


I-O, immuno-oncology regimen.

Progression-free survival

Median PFS in patients post I-O and/or platinum-based chemotherapy5

Progression-free survival5

Progression-free survival Progression-free survival
  • The median follow–up time was 15.3 (1.1–18.4+) months5

Important considerations

  • CodeBreaK 100 was a Phase 2, single-arm, open-label, global, multicenter clinical trial1,2
  • LUMAKRAS™ is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR)1
  • Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)1

Phase 2 data cutoff date: March 15, 2021.5

Censor indicated by vertical bar.5

Study design

CodeBreaK 100: The first trial to demonstrate KRAS G12C as targetable in NSCLC1

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

CodeBreak100 Study Design CodeBreak100 Study Design

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-up8

††Phase 2 portion of CodeBreaK 100.2

‡‡Consistent efficacy results were seen in patients with KRAS G12C mutation, identified in either tissue or plasma specimens.4

§§Of 126 total enrolled subjects, 2 (2%) were unevaluable for efficacy analysis due to the absence of radiographically measurable lesions at baseline.1


CDx, companion diagnostic; 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 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 extra‐thoracic 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

††Phase 2 portion of CodeBreaK 100.2

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

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.