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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Study design Baseline characteristics Efficacy 3-year follow-up

Study design

The first trial to demonstrate KRAS G12C as targetable in NSCLC1,2

The global CodeBreaK 100 study was a single-arm, open-label, multicenter clinical trial that enrolled patients who had progressed on prior therapy1,3

Study Design Graph Study-Design-Graph-mob

*Across both Phase 1 and Phase 2 of the study, 2 subjects without baseline target lesions and 4 subjects without data for post-baseline percent changes are not shown.6,7

†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.3

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

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

Baseline characteristics

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

*Phase 2 portion of CodeBreaK 100.3

PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1.

Efficacy (USPI)

LUMAKRAS® delivered an objective response rate of 36%1

Major efficacy outcomes: ORR and DOR1

In KRAS G12C–mutated locally advanced or metastatic NSCLC following prior therapy (n=124*)1

Blue graphic showing "Objective response rate 36% with details: "n=45 (95% CI: 28-45)," "2% CR (n=2)," "35% PR (n=43). Blue graphic showing Objective response rate 36% with details: n=45 (95% CI: 28-45), 2% CR (n=2), 35% PR (n=43).

+Symbol indicates censoring.
*2 patients did not have measurable lesions at baseline and were ineligible for response assessment.1
†As determined by a BICR according to RECIST v1.1.1
‡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; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer; ORR, objective response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; USPI, United States Prescribing Information.

3-year follow-up post hoc analysis

Global median 3-year follow-up*

Pooled global objective response rate and duration of response in CodeBreaK 100 Phase 1 and 2A (N=172)9

Blue graphic showing objective response rate 41% with 4% CR (n=7) and 37% PR (n=63), median duration of response 12 months (7.1, 15), and 73% of patients responded for 6 months or longer. Blue graphic showing objective response rate 41% with 4% CR (n=7) and 37% PR (n=63), median duration of response 12 months (7.1, 15), and 73% of patients responded for 6 months or longer.
Important considerations9
  • The analysis includes the combined Phase 1 and Phase 2 CodeBreaK 100 study population (N=172) receiving LUMAKRAS® 960 mg daily in NSCLC
  • This analysis was not powered to assess statistically significant differences between the global population and the North American subgroup

*Data cutoff: March 19, 2025.9

†Exact 95% confidence interval was calculated using the Clopper Pearson method.9

‡Duration of response calculated among confirmed responders N1.9

CI, confidence interval; CR, complete response; NSCLC, non-small cell lung cancer; PR, partial response.

North America median 3-year follow-up*

Pooled North America objective response rate and duration of response in CodeBreaK 100 Phase 1 and 2A (N=120)9

Blue graphic showing objective response rate 45% with 5% CR (n=6) and 40% PR (n=48), median duration of response 11 months (7.1, 15), and 71% of patients responded for 6 months or longer. Blue graphic showing objective response rate 45% with 5% CR (n=6) and 40% PR (n=48), median duration of response 11 months (7.1, 15), and 71% of patients responded for 6 months or longer.
Important considerations9
  • The analysis includes combined Phase 1 and Phase 2 CodeBreaK 100 North America population (N=120) receiving LUMAKRAS® 960 mg daily in NSCLC
  • This analysis was not powered to assess statistically significant differences between global population and North American subgroup

*Data cutoff: March 19, 2025.9

†Exact 95% confidence interval was calculated using the Clopper Pearson method.9

‡Duration of response calculated among confirmed responders N1.9

CI, confidence interval; CR, complete response; NSCLC, non-small cell lung cancer; PR, partial response.

Duration of response in global 3-year follow-up9

  • 11% of patients (95% CI: 3.4–23.3) were still in response at a median follow-up of 36 months
      

Pooled global duration of response in CodeBreaK 100 Phase 1 and 2A (N=70)

Bar chart titled Duration of response in global 3-year follow up (N=70). Bars represent ongoing treatments over months, marked with colored symbols for first response, PD, and death. Bar chart titled Duration of response in global 3-year follow up (N=70). Bars represent ongoing treatments over months, marked with colored symbols for first response, PD, and death.

§Patient still in response at time of data cutoff.9
PD, progressive disease.

Learn about LUMAKRAS® safety

Duration of response in North America 3-year follow-up9

  • 13% of patients (95% CI: 3.8–28.3) were still in response at median follow-up of 36 months
      

Pooled North America duration of response in CodeBreaK 100 Phase 1 and 2A (N=54)

Bar chart titled Duration of response in North America 3-year follow-up (N=54). It shows respondents treatment timelines in months, with symbols indicating first response, progression, death, and ongoing treatment. Bar chart titled Duration of response in North America 3-year follow-up (N=54). It shows respondents treatment timelines in months, with symbols indicating first response, progression, death, and ongoing treatment.

§Patient still in response at time of data cutoff.9
PD, progressive disease.

Learn about LUMAKRAS® safety

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; [Trial Sites]. 3. Sotorasib CSR. Amgen; 2021. 4. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03600883?term=NCT03600883&rank=1. Accessed July 2, 2025. 5. Dy GK, et al. Abstract presented at: American Association for Cancer Research Annual Meeting; April 8–13, 2022; New Orleans, LA. 6. Data on file, Amgen; [2-Year Follow-Up]. 7. Data on file, Amgen; [North America]. 8. Data on file, Amgen; 2021. 9. Data on file, Amgen; [Non-controlled Amgen sotorasib 3-year follow-up for Pooled Efficacy].