• In 2021, the U.S. Food and Drug Administration (FDA) approved four new treatments for non-small cell lung cancer (NSCLC) — Tepmetko, Rybrevant, Lumakras and Exkevity.
• These new drugs offer new possibilities for individuals whose lung cancers may have previously had few treatment options.

The list of available treatments for lung cancer expanded this past year as the U.S. Food and Drug Administration granted approval or accelerated approval to four new drugs for NSCLC: Tepmetko (tepotinib), Rybrevant (amivantamab-vmjw), Lumakras (sotorasib), and Exkevity (mobocertinib).

Two of the drugs, Tepmetko and Exkevity, received what’s called accelerated approval. The FDA uses accelerated approval for drugs that fill unmet medical needs, based on whether the drug has demonstrated the potential to have a clinical benefit. For example, a drug may receive accelerated approval if it’s proven capable of shrinking tumors — and later may receive regular approval once it proves it can extend the life of someone living with cancer.

Tepmetko

Tepmetko was given accelerated approval by the FDA on Feb. 3 for treating metastatic NSCLC with mutations in the mesenchymal-epithelial transition (MET) gene. Manufactured by biopharmaceutical company EMD Serono, Tepmetko is the first oral MET inhibitor developed to treat NSCLC. Tepmetko is a tablet taken once daily.

Mutations in MET are found in 2 percent to 4 percent of NSCLC cases. Tepmetko treats NSCLC cases with a specific mutation known as MET exon 14 skipping alterations. This means that part of the gene is skipped over when DNA is replicating, which makes a mutated MET protein.

“There is a pressing need for targeted treatments that have the potential to generate durable anti-tumor activity and improve the lives of patients with this challenging disease,” said Dr. Paul Paik, an oncologist at Memorial Sloan Kettering Cancer Center, in a press release. “Tepmetko offers an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”

Learn more about mutations associated with lung cancer.

Rybrevant

Rybrevant was approved by the FDA on May 21 as the first available treatment for NSCLC cases with epidermal growth factor receptor (EGFR) mutations. The drug is produced by Janssen Biotech.

This drug treats cases with EGFR exon 20 insertions. These are extra pieces of DNA inserted into the EGFR gene, which then create mutated proteins that do not work properly. EGFR exon 20 insertions account for 2 percent to 3 percent of mutations in all NSCLC cases — they are the third most common kind of EGFR mutation.

Rybrevant is an immunotherapy made with antibodies that help activate the body’s immune system against cancer. It comes as a liquid solution that is slowly injected into a vein at a hospital or infusion clinic. This approach is necessary because antibodies cannot be ingested by mouth like many other medications.

“The approval of Rybrevant, along with the companion diagnostic test, addresses high unmet need in the treatment of people with genetically defined non-small cell lung cancer,” said Dr. Peter Lebowitz in a press release from Janssen Pharmaceutical Company.

Rybrevant was approved alongside a genetic test — known as Guardant360 CDx — that is used to confirm that a person’s cancer has an EGFR exon 20 insertion. A small blood sample is taken and sent to a lab, where DNA from tumor cells is isolated and analyzed for mutations.

Lumakras

On May 28, the FDA approved a first-in-class medication — Lumakras — for treating NSCLC with a specific mutation known as KRAS G12C. These mutations account for 13 percent of mutations in all NSCLC cases. The approval was granted to biotech company Amgen.

“KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer,” said Dr. Richard Pazdur, director of the FDA’s Oncology Center of Excellence, said in a press release.

The therapy is approved for treating people with NSCLC with a KRAS G12C mutation, who have received at least one systemic therapy — such as chemotherapy or immunotherapy. Lumakras is available as a tablet taken by mouth once daily.

Exkivity

Exkivity received accelerated approval from the FDA on Sept. 15 as a new treatment for NSCLC. Exkivity, from Takeda Pharmaceuticals, is the first oral therapy available to treat NSCLC with EGFR exon 20 insertions, given once daily as a tablet. Rybrevant, which targets the same mutation, is administered as an intravenous infusion.

Exkivity is indicated for adults with cases of advanced or metastatic NSCLC cases that are worsening on or after platinum-based chemotherapy.

“The approval of Exkivity introduces a new and effective treatment option for patients with EGFR exon 20 insertion+ NSCLC, fulfilling an urgent need for this difficult-to-treat cancer,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda, in a press release.