Initial US Approval

  • 20211

Indications

Metastatic KRAS G12C+ NSCLC:

  • 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 objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).1

Recommended Dose/Route

  • Sotorasib 960 mg orally once daily, with or without food1

Dose Reductions for Adverse Reactions

  • 1st reduction: 480 mg once daily1
  • 2nd reduction: 240 mg once daily1

Pivotal Study

CodeBreaK 100 (NCT03600883)1,2

  • Key Inclusion Criteria: Eligible patients were required to have locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy, an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
  • Treatment: Sotorasib 960 mg orally once daily until unacceptable toxicity or disease progression.
Sotorasib: Efficacy Data

Sotorasib: Efficacy Data

Safety

CodeBreaK 1001,2

  • Common adverse reactions (≥20%): diarrhea (42%), musculoskeletal pain (35%), nausea (26%), fatigue (26%), hepatotoxicity (25%), and cough (20%).
  • Common laboratory abnormalities (≥25%): decreased lymphocytes (48%), decreased hemoglobin (43%), increased aspartate aminotransferase (39%), increased alanine aminotransferase (38%), decreased calcium (35%), increased alkaline phosphatase (33%), increased urine protein (29%), and decreased sodium (28%).
  • Dosage Interruption Due to Adverse Events (AEs): 34%
  • Dosage Reductions Due to AEs: 5%
  • Permanent Discontinuation Due to AEs: 9%
Sotorasib: Most_Common Adverse Events of Grade 3 or 4

Sotorasib: Most_Common Adverse Events of Grade 3 or 4

References

  1. LUMAKRAS (sotorasib). Prescribing information. Amgen, Inc;2023. Accessed December 10. 2024. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Lumakras/lumakras_pi_hcp_english.pdf
  2. Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021; 384:2371-2381. doi:10.1056/NEJMoa2103695
  3. Dy GK, Ramaswamy G, Velcheti V, et al. Long-term outcomes and molecular correlates of sotorasib efficacy in patients with pretreated KRAS G12C-mutated non-small-cell lung cancer: 2-year analysis of CodeBreaK 100. J Clin Oncol. 2023; 41:3311-3317. doi:10.1200/JCO.22.02524
  4. Chour A, Basse C, Lebossé F, Bonte PE, Girard N, Duruisseaux M. Management of sotorasib-related adverse events and hepatotoxicities following anti-PD-(L)1 therapy: experience with sotorasib in two French anti-cancer centers and practical guidance proposal. Lung Cancer. 2024;191:107789. doi:10.1016/j.lungcan.2024.107789
  5. Zhang J, Johnson M, Barve M, et al. Practical guidance for the management of adverse events in patients with KRASG12C-mutated non-small cell lung cancer receiving adagrasib. Oncologist. 2023;28(4):287-296. doi:10.1093/oncolo/oyad051