FDA Approves Lumakras For Non-Small Lung Cancer



The U.S. Food and Drug Administration on May 28, 2021 approved Lumakras (Sotorasib) as the first therapy for adult patients with non-small cell lung cancer whose tumors have a unique type of genetic mutation known as KRAS G12C and who have been administered a minimum of one prior systemic therapy.


This is the first approved targeted treatment for tumors with any KRAS mutation, which is responsible for about 25% of mutations in non-small cell lung cancers. KRAS G12C mutations account for approximately 13% of mutations in non-small cell lung cancers.


“KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer,” disclosed Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.


“Today’s approval represents a significant step towards a future where more patients will have a personalized treatment approach.”


Lung cancer, the most prevalent type of cancer with the highest mortality rate, can primarily be defined by the genetic mutations that cause it. KRAS is a form of mutation in a group of genes that is responsible for regulating cell growth and division.


Researchers looked into the efficacy of Lumakras in a study of 124 patient 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 primary outcomes measured were objective response rate (proportion of patients whose tumor is reduced or destroyed) 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 premised on available clinical data, as well as pharmacodynamics and pharmacokinetic modeling that aid the approved dose. In line with the evaluation for this speedy approval, the agency is requesting a postmarketing trial to test whether a lower dose will have the same clinical effect.


The most prevalent side effects of Lumakras include nausea, fatigue, cough, liver damage, diarrhea and musculoskeletal pain. The drug should be halted if patients show signs of interstitial drug disease and permanently discontinued if interstitial lung disease is ascertained. Health care professionals should monitor a patient’s liver function tests before beginning and when administering Lumakras. If a patients suffers liver damage, Lumakras should be paused, dose lowered or permanently stopped. Patients should not take acid-reducing agents, drugs that induce or are substrates for some enzymes in the liver and drugs that are substrates of the P-glycoprotein while on Lumakras.


Lumakras was approved through the Accelerated Approval pathway, under which the FDA may approve medications for severe conditions where there is unsatisfied medical need and a drug is proven to have specific effects that are reasonable likelihood to predict a clinical benefit to patients. More study is needed to verify and describe anticipated clinical advantages of Lumakras.


The FDA granted this application Fast Track, Breakthrough Therapy and Priority Review designations.


Lumakras also got Orphan Drug designation, which offers incentives to assist and encourage the development of medications for rare diseases.



This review was undertaken under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis offers a framework for simultaneous submission and review of oncology medications among international collaborators. For this review, FDA partnered with the Australian Therapeutic Goods Administration (TGA), Healthcare Products Regulatory Agency (MHRA; United Kingdom) and the Brazilian Health Regulatory Agency (ANVISA), Health Canada and Medicines. The review of applications are ongoing at other regulatory bodies.


The FDA granted approval of Lumakras to Amgen Inc.

Apart from Lumakras, the FDA also granted approval to the Guardant360 CDx (approval granted to Guardant Health, Inc.) and the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) as companion diagnostics for Lumakras. The QIAGEN GmbH test evaluates tumor tissue and the Guardant Health, Inc. looks into plasma specimens to assess if Lumakras is appropriate therapy for patients. If no mutation is found in a plasma specimen, the patient’s tumor should be tested.