Janssen Submits BLA for Metastatic Lung Cancer Treatment

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. The application marks the first-ever regulatory submission for the treatment of patients with NSCLC with EGFR exon 20 insertion mutations. The Company has also established an expanded access program (EAP) for patients in the U.S. who may be eligible to obtain access to amivantamab during review of the BLA.

Amivantamab is an investigational, fully-human EGFR and mesenchymal epithelial transition factor (MET) bispecific antibody with immune cell-directing activity that targets tumors with activating and resistance EGFR and MET mutations and amplifications. In March 2020, amivantamab received Breakthrough Therapy Designation from the FDA for this population.

"This submission marks an important step forward in our drive toward evolving the treatment landscape for patients with NSCLC who have EGFR exon 20 insertion mutations and for whom there are no FDA-approved targeted treatment options," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "We are committed to the development of therapies like amivantamab that progress precision medicine and target specific pathways, and to providing access through expanded access programs."

The BLA submission for amivantamab is based on data from the monotherapy arm of the Phase 1 CHRYSALIS study, a multi-center, open-label, multi-cohort study evaluating the safety and efficacy of amivantamab as a monotherapy and in combination with lazertinib, a novel third-generation EGFR tyrosine kinase inhibitor (TKI), in adult patients with advanced NSCLC. In the study, investigators assessed efficacy using overall response rate per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), clinical benefit rate, and duration of response and progression-free survival, as well as the safety profile of amivantamab.

"Lung cancer remains the leading cause of cancer deaths worldwide. Given this significant unmet need, we at Johnson & Johnson are committed to improving outcomes for patients diagnosed with this complex, deadly disease. With today's submission for amivantamab, we are one step closer to that goal," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. "We are steadfast in our focus to advance novel therapeutics and medicines that will transform the trajectory of some of the most challenging and deadly diseases of our time, including lung cancer."

EGFR mutations, leading to uncontrolled cancer cell growth and division, are some of the most common mutations in NSCLC. EGFR exon 20 insertion mutations are the third most prevalent primary EGFR mutation. However, EGFR exon 20 insertion mutations are also often undetected. Next Generation Sequencing (NGS) is effective at detecting EGFR exon 20 insertion mutations and broader use of NGS can help to detect these mutations. Cancer driven by EGFR exon 20 insertion mutations is generally insensitive to approved EGFR TKI treatments and, in addition, carries a worse prognosis compared with cancer driven by more common EGFR mutations, including exon 19 deletions/L858R substitutions. Patients with EGFR exon 20 insertion mutations have a median survival of less than 17 months, which is much shorter than patients with EGFR exon 19 deletions or L858R mutations, who have a median survival of 32-39 months.

Amivantamab is an investigational, fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumors with activating and resistance EGFR mutations and MET mutations and amplifications. Amivantamab is pending regulatory review as a potential treatment for patients with NSCLC with EGFR exon 20 insertion mutations whose tumors typically do not respond to current standard of care. Companion diagnostics to identify patients with EGFR exon 20 insertion mutations have been an integral part of the development program for amivantamab. The production and development of the antibody followed Janssen Biotech's licensing agreement with Genmab for use of its DuoBody® technology platform.