RARE Daily

FDA Approves First Therapy for Rare Form of NSCLC with Companion Diagnostic

May 25, 2021

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Janssen Pharmaceutical’s Rybrevant, the first targeted treatment for adults with non-small cell lung cancer with EGFR Exon 20 insertion mutations detected by an FDA approved test.

The FDA simultaneously approved Guardant Health’s Guardant360 CDx liquid biopsy blood test as a companion diagnostic for use with Rybrevant.

Lung cancer is the leading cause of cancer death among both men and women, accounting for almost 25 percent of all cancer deaths. Currently available targeted treatments, like EGFR tyrosine kinase inhibitors are generally insensitive in treating NSCLC driven by EGFR exon 20 insertion mutations and are not FDA-approved for these patients. In addition, NSCLC driven by this mutation carries a worse prognosis and shorter survival rates compared with lung cancer driven by more common EGFR mutations. Patients newly diagnosed with metastatic NSCLC with EGFR exon 20 insertion mutations have a real-world median overall survival (OS) of 16.2 months.

Rybrevant is the first fully-human, bispecific antibody approved for the treatment of patients with NSCLC that targets EGFR exon 20 insertion mutations, which are the third most prevalent activating EGFR mutation. Today’s approval follows the FDA’s decision to grant Breakthrough Therapy designation in March 2020 and to initiate a Priority Review of the Biologics License Application in December 2020. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Approval was based on CHRYSALIS, a multicenter, non-randomized, open label, multicohort clinical trial that included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Efficacy was evaluated in 81 patients with advanced NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. Patients received Rybrevant once weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate (ORR) according to RECIST 1.1 as evaluated by blinded independent central review and response duration. The ORR was 40 percent with a median response duration of 11.1 months.

The regulatory review of Rybrevant was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Brazilian Health Regulatory Agency and United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.

“Today’s FDA approval is an important development for people living with non-small cell lung cancer with exon 20 insertion mutations who, until now, have had no approved treatment options to target their disease,” said Jill Feldman, co-founder of the EGFR Resisters, an advocacy organization patient group, and a lung cancer patient advocate. “We are excited by the promise this new treatment option brings to people with this particular type of lung cancer and their families.”

Photo: Jill Feldman, co-founder of EGFR Resisters

Stay Connected

Sign up for updates straight to your inbox.