FDA Approval: Sotorasib (Lumakras) for Lung Cancer

A target that was called undruggable

For decades KRAS was known as the root cause of cancer in hundreds of thousands of people, and for decades nobody could block it. The protein was widely described as undruggable.

On May 28, 2021, that changed. The FDA granted accelerated approval to sotorasib, sold as Lumakras, the first drug that blocks a mutant KRAS protein. Its FDA label carries an Initial U.S. Approval date of 2021.

The break came from better understanding of the protein's shape, paired with new chemistry. NCI's account quotes Frank McCormick of NCI's RAS Initiative calling it a big breakthrough in the whole field.

What the 2021 approval covered

The approval was narrow and specific. Sotorasib could be used for non-small cell lung cancer that had spread nearby, meaning locally advanced, or to distant sites, meaning metastatic. Patients had to have received at least one prior systemic treatment, such as chemotherapy. And their tumor had to carry one particular KRAS mutation, G12C.

About 13 percent of people with NSCLC have the G12C mutation. It is a hallmark of damage from cigarette smoke. It also appears less often in colorectal cancer and in a small share of pancreatic cancers.

The FDA approved two tests alongside the drug. The Qiagen therascreen KRAS RGQ PCR kit checks tumor tissue. Guardant360 CDx checks blood. A test like this, tied to a specific drug decision, is called a companion diagnostic. Our page on biomarker testing explains the category.

The trial

The approval rested on early results from CodeBreaK 100, a study funded by Amgen and NCI. The reported group was 124 people with KRAS G12C-mutant NSCLC who had already had other treatments. Most had received immunotherapy, chemotherapy, or both. Everyone in the study got sotorasib, taken as a pill once a day.

Tumors shrank in 36 percent of participants. Those responses lasted a median of 10 months.

NCI put that beside the alternative. Standard therapies shrink tumors in fewer than 20 percent of people whose NSCLC has come back after previous treatment, and those effects are usually short-lived.

The strings attached

Accelerated approval is a conditional route. It lets the FDA clear a drug for a serious condition based on a measure that is reasonably likely to predict benefit, rather than on proof of longer life.

Here the measure was tumor shrinkage in a single-arm study. As a condition of approval, Amgen had to run a further trial to confirm that the drug helps people with NSCLC live longer without the cancer worsening. A larger study comparing sotorasib with standard chemotherapy was under way at the time of approval.

That condition still appears on the label today. NCI notes that the NSCLC use remains under the Accelerated Approval Program, with confirmatory trials required to show clinical benefit. Our page on clinical trial phases explains how those later studies are built.

The label has since grown. NCI also lists sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer that has spread, in people who previously received chemotherapy containing a fluoropyrimidine, oxaliplatin, and irinotecan.

When to get checked

The G12C mutation is tied to tobacco damage, so the screening question matters here.

A yearly low-dose CT scan is recommended for adults aged 50 through 80 who have a 20 pack-year smoking history and who currently smoke or quit within the past 15 years. Screening stops once a person has not smoked for 15 years, or develops a health problem that substantially limits life expectancy or the ability to have curative lung surgery.

Symptoms are a separate track and should not wait for a scheduled scan. NCI lists chest discomfort or pain, a cough that does not go away or worsens, trouble breathing, wheezing, blood in coughed-up mucus, hoarseness, loss of appetite, unexplained weight loss, fatigue, trouble swallowing, and swelling in the face or neck veins.

How advanced NSCLC is worked up

Tests to detect, diagnose, and stage lung cancer are usually done at the same time. Imaging maps the lung and surrounding tissue, and a biopsy confirms the diagnosis.

Stage runs from occult and stage 0 through stage IV, based on tumor size, spread within the chest, and spread beyond it. Molecular testing on the tissue is now part of the standard workup for advanced disease, because it decides whether a targeted drug is an option at all.

NCI lists gene changes such as EGFR and ALK among the factors that shape prognosis and treatment options. KRAS G12C now sits on that same list of decision points.

The population these results sit inside

These SEER figures cover everyone with lung and bronchus cancer. People with KRAS G12C tumors are a subgroup inside that, so the numbers do not describe them specifically, and they describe no individual.

Five-year relative survival is 29.5 percent for cases from 2016 to 2022. By stage it is 65.5 percent for cancer confined to the lung, 38.2 percent when it has reached nearby lymph nodes, and 10.5 percent once it has spread further. Just 24 percent are caught at that first stage, and 51 percent are already distant at diagnosis. An estimated 229,410 new cases and 124,990 deaths are projected for 2026.

Our page on lung cancer covers the disease in full.

What this does not mean

A first drug against a target is a scientific milestone, not a finished answer. A 36 percent response rate means most people in that trial did not have their tumors shrink. A median response duration of 10 months describes the middle of a range, not a promise.

Sotorasib blocks one KRAS mutation, G12C. Other KRAS mutations exist and are not covered. And whether the drug fits one person depends on the tumor test result, prior treatments, other medicines, and side effects.

Sources

• NCI Cancer Currents, FDA approval of sotorasib for KRAS G12C lung cancer — https://www.cancer.gov/news-events/cancer-currents-blog/2021/fda-sotorasib-lung-cancer-kras
• NCI, Sotorasib — https://www.cancer.gov/about-cancer/treatment/drugs/sotorasib
• FDA, sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer — https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer
• DailyMed, LUMAKRAS (sotorasib) label — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c80a362c-7ac3-4894-a076-0691e68ef8c1
• NCI PDQ, Non-Small Cell Lung Cancer Treatment (Patient Version) — https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq
• SEER Cancer Stat Facts, Lung and Bronchus Cancer — https://seer.cancer.gov/statfacts/html/lungb.html
• USPSTF, Lung Cancer: Screening — https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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