LUMAKRAS? Receives FDA Approval

Today is a big day for Amgen and, more importantly, for patients with lung cancer. The U.S. FDA has approved LUMAKRAS? (sotorasib), a first-in-class treatment for people with certain non-small cell lung cancers that express the KRASG12C mutation. This is one of the most common genetic mutations in non-small cell lung cancer, accounting for some 13 percent of all cases. For decades, the KRAS protein was thought to be “undruggable,” but Amgen researchers found a way to do it. They identified a previously hidden crevice on the surface of the KRASG12C protein and then engineered a molecule that could exploit this crevice in order to attach to the protein and do its therapeutic work. 

LUMAKRAS went from proof-of-concept to regulatory approval in just 28 months. That represents the fastest clinical development program in Amgen’s history, and one of the fastest for our entire industry. This feat is all the more remarkable in view of the hurdles posed by COVID-19 to our clinical development team over the past year and a half. 

Click here to read more about this milestone. My congratulations and thanks to the many people – including Amgen scientists, independent investigators, hospital care teams, and patients and their family members – who helped to get this new treatment through clinical development and regulatory approval and available to patients so quickly.

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).

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. 

Please see accompanying LUMAKRAS? full Prescribing Information.