Supplemental Biologics License Application Submitted to Expand Approval of Rybrevant for NSCLC

Janssen Pharmaceuticals has submitted a supplemental biologics license application (sBLA) to the FDA seeking to expand the approval of amivantamab-vmjw (Rybrevant) in combination with carboplatin-pemetrexed for the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.1 The sBLA is currently being reviewed by the FDA through the Real-Time Oncology Review program, according to a statement from Janssen.¹

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“PAPILLON is the first randomized phase 3 study in patients with NSCLC with EGFR exon 20 insertion mutations to show clinically meaningful results. This creates an opportunity to make a significant improvement to the standard of care for this patient population with high unmet medical need,” Kiran Patel, MD, vice president of clinical development for solid tumors at Janssen Research & Development LLC., said in the statement.¹

The sBLA is supported by data from the phase 3 PAPILLON trial (NCT04538664), evaluating the efficacy and safety of the drug in combination with chemotherapy for this patient population.¹ In July, it was announced that the study met its primary endpoint with a statistically significant and clinically meaningful improvement in progression free survival (PSF) when compared to chemotherapy alone.^1,2

The secondary endpoints included overall response rate, overall survival, PFS after subsequent therapy, and time to progression of symptoms.² Additionally, the combination demonstrated a safety profile consistent with the individual components.^1,2

In the study, investigators reported that the most common low-grade adverse events (AEs) included rash, infusion-related reactions, and paronychia.² There were 2% of individuals who experienced severe AEs, which were grades 3 and 4, and included decreased lymphocytes, albumin, phosphate, and increased alkaline phosphatse.²

Amivantamab-vmjw received accelerated approval in 2021, following its breakthrough therapy designation, and was the first fully human, bispecific antibody for the treatment of patients with NSCLC with EGFR exon 20 insertion. The sBLA submission is also intended to meet the regulatory requirements of the accelerated approval that confirms the clinical benefit observed in the phase 1 CHRYSALIS study, according to the statement.¹

Approximately 10% to 15% of lung cancers in the United States are EGFR-positive, generally appearing in adenocarcinoma subtype of NSCLC, according to the American Lung Association.³ Additionally, individuals with lung cancer who have EGFR mutations tend to have minimal to no smoking history; however, the mutation can appear in any lung cancer with different subtypes as well as in those with smoking history.³

The EGFR protein that helps cells grow, so a mutation in the gene EGFR can cause the cell to grow too much and cause cancer. EGFR exon 20 insertion is a rarer type of EGFR mutation, and does not respond to the typical treatment for EGFR-positive lung cancer, such as tyrosine kinase inhibitors.³

References

1. Janssen submits supplemental biologics application to the US Food and Drug Administration seeking approval of Rybrevant (amivantamab-vmjw) in combination with chemotherapy for the first-line treatment of patients with locally advanced or metastatic EGFR exon 20 insertion mutation-positive non–small cell lung cancer. News release. Johnson & Johnson. August 25, 2023. Accessed August 28, 2023. https://www.jnj.com/janssen-submits-supplemental-biologics-license-application-to-the-u-s-food-and-drug-administration-seeking-approval-of-rybrevant-amivantamab-vmjw-in-combination-with-chemotherapy-for-the-first-line-treatment-of-patients-with-locally-advanced-or-metastatic-egfr-exon-20-insertion-mutation-positive-non-small-cell-lung-cancer
2. Hunter E. Confirmatory PAPILLON study supports amivantamab-vmjw for patients with severe lung cancer mutation. Pharmacy Times. July 19, 2023. Accessed August 28, 2023. https://www.pharmacytimes.com/view/confirmatory-papillon-study-supports-amivantamab-vmjw-for-patients-with-severe-lung-cancer-mutation
3. American Lung Association. EGFR and lung cancer. Updated November 17, 2022. Accessed August 28, 2023. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr#:~:text=Who%20is%20likely%20to%20have,minimal%20to%20no%20smoking%20history.