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

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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

Median 2-year follow-up*

A descriptive analysis of the CodeBreaK 100 study evaluating the efficacy of LUMAKRAS in patients with locally advanced or metastatic KRAS G12C–mutated NSCLC from across the globe. The study included 174 patients from the Phase 1 (n=48) and Phase 2 (n=126) portions. Efficacy outcomes included objective response rate as evaluated by BICR according to RECIST v1.1, duration of response, and disease control rate (n=172†). Other efficacy outcomes were depth of response (n=168†,‡), overall survival (N=174), and progression-free survival (n=172†).3 The prespecified North Amercian subgroup (N=120) included patients from USA (n=114) and Canada (n=6), with longer follow-up data with a median of 2 years.4

*Data cutoff: February 22, 2022. Median follow-up for PFS and OS was 21.9 and 24.9 months, respectively.3

†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4

‡4 patients did not have data for postbaseline percent changes.3,4

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-up8

†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4

§§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.3

†††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

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 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
  • The baseline characteristics of the pooled global and North American Phase 1 and 2 portion of the study population at 960 mg are consistent with the population in the US Prescribing Information4

‡‡‡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% 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

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
  • Global
  • North America

Median 2-year follow-up*

LUMAKRAS® (sotorasib) objective response rate and disease control rate median at two-year follow-up

LUMAKRAS® (sotorasib) objective response rate and disease control rate median at two-year follow-up


  • No new safety findings were observed for this pooled study population6

Important considerations3

  • This is a descriptive analysis of pooled data from the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 study population receiving 960 mg in NSCLC
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

Median 2-year follow-up*

LUMAKRAS® (sotorasib) objective response rate and disease control rate median at two-year follow-up

LUMAKRAS® (sotorasib) objective response rate and disease control rate median at two-year follow-up


  • No new safety findings were observed for this pooled study population4

Important considerations4

  • This is a descriptive analysis of subgroups in the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC North America study population receiving 960 mg
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

+Symbol indicates censoring.

*Data cutoff: February 22, 2022. Median follow-up for PFS and OS was 21.9 and 24.9 months, respectively.3

†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4

§As determined by a BICR according to RECIST v1.1.1,6

**Disease control rate = CR + PR + stable disease.

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


BICR, blinded independent central review; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; USPI, United States Prescribing Information.

Depth of response

  • Global
  • North America

84% of patients had tumors remain stable or shrink while on LUMAKRAS6

2-year best tumor change from baseline (n=168)3,†,‡

Two-year best tumor change from baseline
Two-year best tumor change from baseline

85% of patients had tumors remain stable or shrink while on LUMAKRAS4

2-year best tumor change from baseline (n=116)4,‡

North America patients depth of response
North America patients depth of response
  • Disease control rate observed in 84% (144/172;† 95% CI: 77–89) of patients6
  • Complete response observed in 3% (5/172†) of patients6
  • Disease control rate observed in 85% (102/120; 95% CI: 77–91) of patients4
  • Complete response observed in 4% (5/120) of patients4

Important considerations3

  • This is a descriptive analysis of pooled data from the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 study population receiving 960 mg in NSCLC
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.6
  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.3
  †2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4
‡4 patients did not have data for postbaseline percent changes.3,4
  BOR, best overall response; NE, not evaluable; PD, progressive disease; SD, stable disease.

Important considerations4

  • This is a descriptive analysis of subgroups in the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC North America study population receiving 960 mg
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4
  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.4
  ‡4 patients did not have data for postbaseline percent changes.3,4

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

Overall survival

  • Global
  • North America

Overall survival in patients receiving LUMAKRAS post–I-O and/or platinum-based chemotherapy6

2-year overall survival

Overall survival in patients receiving LUMAKRAS® (sotorasib) post-I-0 and/or platinum-based chemotherapy Overall survival in patients receiving LUMAKRAS® (sotorasib) post-I-0 and/or platinum-based chemotherapy

Landmark and median overall survival in patients receiving LUMAKRAS post–I-O and/or platinum-based chemotherapy4

2-year overall survival

North American patients median overall survival North American patients median overall survival
  • The median follow-up time was 24.9 (95% CI: 23.5–26) months6
  • One- and two-year OS was 51% and 33%6

Important considerations3

  • This is a descriptive analysis of pooled data from the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 study population receiving 960 mg in NSCLC
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.6

 

Censor indicated by vertical bar. Death is an event.3

I-O, immuno-oncology regimen.

  • The median follow-up time was 24.9 (95% CI: 23.5–26.3) months4
  • One- and two-year OS was 53% and 36%4

Important considerations4

  • This is a descriptive analysis of subgroups in the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC North America study population receiving 960 mg
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4

 

Censor indicated by vertical bar. Death is an event.4

I-O, immuno-oncology regimen.

Progression-free survival

  • Global
  • North America

Median PFS in patients receiving LUMAKRAS post–I-O and/or platinum-based chemotherapy6

2-year progression-free survival6

Median PFS in patients receiving LUMAKRAS® (sotorasib) post-I-0 and/or platinum-based chemotherapy Median PFS in patients receiving LUMAKRAS® (sotorasib) post-I-0 and/or platinum-based chemotherapy
  • The median follow-up time was 21.9 (95% CI: 19.3–24.9) months3

Important considerations3

  • This is a descriptive analysis of pooled data from the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 study population receiving 960 mg in NSCLC
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.6

 

Censor indicated by vertical bar.3

†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4

  • The median follow-up time was 21.9 (95% CI: 18.2–24.9) months4

Important considerations4

  • This is a descriptive analysis of subgroups in the CodeBreaK 100 study using prespecified endpoints
  • The analysis includes the combined Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC North America study population receiving 960 mg
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4

 

Censor indicated by vertical bar.4

  • Global
  • North America

Consistent efficacy was seen across prespecified subgroups7

2-year efficacy in subgroups by baseline characteristics7

Two-year efficacy in subgroups by baseline characteristics Two-year efficacy in subgroups by baseline characteristics

  • 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 subgroups7

‡‡A total of 174 patients received 960 mg from the Phase 1 (n=48/174) and Phase 2 study (n=126/174). 2 patients did not have measurable lesions at baseline and were ineligible for response assessment.7

ECOG PS, Eastern Cooperative Oncology Group performance status; mOS, median overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 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.