FDA Approves Janssen’s Targeted Non-Small Cell Lung Cancer Therapy

FDA recently approved Janssen’s Rybrevant as the first targeted therapy for patients with subset of non-small cell lung cancer. 

The agency approved the therapy based on a study of 81 patients with non-small cell lung cancer and EGFR exon 20 insertion mutations whose disease had progressed during or after platinum-based chemotherapy.

The main outcome of the study was overall response rate, which was the proportion of patients whose tumors were destroyed or reduced by Rybrevant. 

In the trial, Rybrevant elicited an overall response rate of 40 percent. The median duration of response was 11.1 months, with 63 percent of patients having a response time of six months or more. 

The most common side effects of the therapy included rash, infusion-related reactions, shortness of breath, nausea, fatigue cough, vomiting, changes in some blood tests, and skin, muscle, and joint pain.

“Advances in precision oncology continue to facilitate drug development, allowing diseases like lung cancer to be subset into biomarker-defined populations appropriate for targeted therapies,” Julia Beaver, MD, chief of medical oncology in the FDA’s Oncology Center of Excellence, said in the announcement. 

“With today’s approval, for the first time, patients with non-small cell lung cancer with EGFR exon 20 insertion mutations will have a targeted treatment option,” continued Beaver who as serves as acting deputy director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. 

FDA stated that Rybrevant should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed. Additionally, patients taking the therapy should limit sun exposure for two months after treatment.

Rybrevant may also negatively affect pregnant women, therefore, the pregnancy status of females of reproductive potential should be confirmed prior to treatment, FDA stated in the approval. 

Rybrevant received priority review and breakthrough therapy designation for this indication.

This review was conducted under project orbis, an initiative of the FDA Oncology Center of Excellence, the agency explained. 

In addition to Rybrevan’t approval, FDA approved Guardant360 CDx as a companion diagnostic for the therapy. 

Guardant360 CDx is a lab test that detects genetic mutations found in circulating cell-free DNA (cfDNA) to help doctors identify patients with non-small cell lung cancer who should be treated with Tagrisso.

Tagrisso is AstraZeneca’s prescription drug for the treatment of patients with early-stage epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer. 

Currently, Tagrisso is approved to treat early-stage lung cancer in over 12 countries, including the US. 

"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," Peter Lebowitz, MD, PhD, global therapeutic area head of oncology at Janssen, said in a statement following the approval. 

"At Janssen, we are committed to the development of innovative therapies like RYBREVANT and believe that advancing medicines targeting specific pathways can bring the greatest benefits and improve outcomes for patients with tumor alterations such as EGFR and MET,” Lebowitz continued. 

Approximately two to three percent of patients with non-small cell lung cancer will have EGFR exon 20 insertion mutations, an FDA spokesperson said.  Consequently, these proteins help cancer spread. EGFR exon 20 insertion mutations are the third most common type of EGFR mutation.

Non-small cell lung cancer accounts for between 80 percent and 85 percent of all lung cancers and is therefore a “lucrative yet competitive space” for pharmaceutical companies, Reuters recently reported in The New York Times.

Keytruda from Merck & Co Inc currently dominates the non-small cell lung cancer space, but a flurry of new FDA approvals is bringing new market entrants. In addition to the approval of Roche’s Tecentriq in May 2020, FDA has also approved Bristol-Myers Squibb Co's Opdivo and Yervoy combination for use in previously untreated patients with non-small cell lung cancer.