Amgen Inc. — Lumakras FDA Review (NDA214665, ORIG 1, 2021)
Amgen Inc. · 2021 · FDA Review (openFDA) · company profile →
Report summary
The FDA's multi-disciplinary review of Amgen's Lumakras (sotorasib) for KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) led to accelerated approval. This decision, under Project ORBIS, was based on the CodeBreak 100 study, which demonstrated a 36% objective response rate and a 10-month median duration of response in previously treated patients. Lumakras received Orphan Drug, Fast Track, and Breakthrough Therapy designations. Nonclinical studies identified liver and kidney as target organs for toxicity, with potential embryo-fetal developmental effects at high doses. Pharmacokinetic analyses revealed a non-linear dose-exposure relationship and potential drug-drug interactions. Safety concerns included increased liver enzymes and pneumonitis, addressed in product labeling. The FDA recommended accelerated approval with post-marketing studies to confirm clinical benefit, optimize dosage, and further characterize safety.
Key findings — cited to the page
| Grade ≥ 3 adverse events (FDA assessment) | 59 % | · p.189 |
| Grade ≥3 treatment-emergent adverse events | 58.8 % | LUMAKRAS (sotorasib) · p.191 |
| increased ALT (Grade ≥ 3) in NSCLC patients | 7.8 % | · p.189 |
| diarrhea (Grade ≥ 3) in NSCLC patients | 5.4 % | · p.189 |
| pneumonia (Grade ≥ 3, FDA assessment) | 7 % | · p.189 |
| diarrhea (Grade ≥ 3, FDA assessment) | 5 % | · p.189 |
| ALT increased (all grades) | 20 % | Sotorasib 960mg QD in NSCLC · p.199 |
| Grade ≥ 3 adverse events (NSCLC) | 58.8 % | · p.189 |
| increased AST (Grade ≥ 3) in NSCLC patients | 6.9 % | · p.189 |
| pneumonia (Grade ≥ 3) in NSCLC patients | 6.4 % | · p.189 |
| musculoskeletal pain (Grade ≥ 3, FDA assessment) | 8 % | · p.189 |
| Grade ≥3 treatment-related treatment-emergent adverse events | 20.6 % | LUMAKRAS (sotorasib) · p.191 |
Source: Amgen Inc. ↗ · License: US Government public domain. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Oncology library →