The U.S. Food and Drug Administration ( FDA ) has approved Lumakras ( Sotorasib ) as the first treatment for adult patients with non-small cell lung cancer whose tumors have a specific type of genetic mutation called KRAS G12C and who have received at least one prior systemic therapy.
This is the first approved targeted therapy for tumors with any KRAS mutation, which accounts for approximately 25% of mutations in non-small cell lung cancers. KRAS G12C mutations represent about 13% of mutations in non-small cell lung cancers.
Lung cancer, the most common cancer type with the highest mortality, can largely be categorized by the genetic mutations that cause it. KRAS is a type of mutation in a group of genes that help regulate cell growth and division.
The efficacy of Lumakras was evaluated in a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer with disease progression after receiving an immune checkpoint inhibitor and/or Platinum-based chemotherapy.
The major outcomes measured were objective response rate ( proportion of patients whose tumor is destroyed or reduced ) and duration of response.
The objective response rate was 36% and 58% of those patients had a duration of response of six months or longer.
The approved 960 milligram dose is based on available clinical data, as well as pharmacokinetic and pharmacodynamic modeling.
As part of the evaluation for this accelerated approval, the Agency has required a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.
The most common side effects of Lumakras include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage and cough.
Lumakras should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed.
Health care professionals should monitor a patient’s liver function tests prior to starting and when taking Lumakras. If a patient develops liver damage, Lumakras should be withheld, dose reduced or permanently discontinued.
Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver and drugs that are substrates of the P-glycoprotein while taking Lumakras.
Lumakras was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Lumakras.
Lumakras has also received Orphan Drug designation. ( Xagena )
Source: FDA, 2021