Janssen's Rybrevant Promises Hope for NSC Lung Cancer Patients and Applies to the FDA

21 November 2023

Janssen has submitted a supplemental application to the FDA for Rybrevant combined with chemotherapy, targeting advanced non-small cell lung cancer patients with EGFR mutations after osimertinib therapy. Supported by Phase 3 MARIPOSA-2 study results, this combination demonstrated significant improvement in progression-free survival.

In a groundbreaking development for lung cancer treatment, Janssen, has submitted a supplemental Biologics License Application to the US Food and Drug Administration (FDA). This application seeks approval for Rybrevant (amivantamab) in combination with chemotherapy for treating patients with a specific form of non-small cell lung cancer (NSCLC). This combination significantly improved progression-free survival compared to chemotherapy alone.

EGFR-Mutated Non-Small Cell Lung Cancer

The submission specifically aims to treat patients with epidermal growth factor receptor (EGFR)-mutated NSCLC, a common and aggressive form of lung cancer. These patients often see their disease progress even after treatment with osimertinib, an existing medication for this cancer type.

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Dr. Kiran Patel, M.D., Vice President at Janssen R&D, emphasizes the urgent need for new treatment options in the post-osimertinib setting, where survival rates remain a concern, and pointed out,

"As we strive to transform the standard of care in patients with EGFR-mutated NSCLC, we are committed to working closely with the FDA during review of this submission for Rybrevant in this expanded patient population."

The Phase 3 MARIPOSA-2 study

The submission is backed by data from the Phase 3 MARIPOSA-2 study, recently presented at the European Society of Medical Oncology (ESMO) 2023 Congress and published in the Annals of Oncology. This pivotal study involved 657 patients with advanced NSCLC and showed significant improvement in progression-free survival when treated with Rybrevant plus chemotherapy compared to chemotherapy alone.

Objective response rate was significantly higher for amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy versus chemotherapy (64% and 63% versus 36%). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy versus chemotherapy.

Rybrevant is a bispecific antibody targeting EGFR and MET, previously granted accelerated approval by the FDA in May 2021 for a specific subset of NSCLC patients. Its potential expansion to treat more lung cancer patients highlights a significant stride in oncological therapeutics.

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Comprehensive Treatment Evaluation

Notably, the MARIPOSA-2 study included rigorous assessments like serial brain imaging for a robust evaluation of the treatment's efficacy, including its activity within the central nervous system – a crucial factor given the severe implications of brain metastases in lung cancer.

In addition to MARIPOSA-2, Rybrevant is undergoing various clinical trials, assessing its efficacy in different combinations and treatment settings for NSCLC. These studies underline the ongoing effort to refine and expand treatment options for lung cancer patients.

This submission marks a potential turning point in treating EGFR-mutated NSCLC. With the FDA's approval, Rybrevant plus chemotherapy could become a new standard of care, offering renewed hope to patients who have limited options after their disease progresses following initial treatments.

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About Rybrevant

Rybrevant (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, received accelerated approval by the U.S. Food and Drug Administration (FDA) in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.2 This indication is approved under accelerated approval based on ORR and DOR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Rybrevant® is also approved in this indication in Europe, and other markets around the world. In August 2023, Janssen submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration for the expanded approval of RYBREVANT® in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations. A marketing authorization application for this indication has also been submitted to the European Medicines Agency.