Janssen Seeks FDA Approval of Amivantamab for Metastatic NSCLC With EGFR Exon 20 Insertion Mutations

Data from the Phase I CHRYSALIS trial also support an expanded access program that makes some patients eligible for amivantamab treatment while the FDA reviews the submission.

Janssen Pharmaceutical Companies of Johnson & Johnson announced the submission of a biologics license application (BLA) seeking FDA approval of amivantamab for the treatment of metastatic non small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutations with disease progression while on or after treatment with platinum-based chemotherapy.1

Amivantamab, a fully-human EGFR and mesenchymal epithelial transition factor (MET) bispecific antibody with immune cell-directing activity, targets tumors with activating and resistance EGFR and MET mutations and amplifications. The investigational drug received breakthrough therapy designation from the FDA for the indicated patient population in March, and this BLA submission is the first regulatory submission for the treatment of NSCLC with EGFR exon 20 insertion mutations.

EGFR mutations are some of the most common in NSCLC, and EGFR exon 20 insertion mutations are the third most common primary EGFR mutation. They often go undetected, but broader use of next generation sequencing could help identify more patients with EGFR exon 20 insertion mutations.

“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,” Peter Lebowitz, MD, PhD; global therapeutic area head, oncology, Janssen Research & Development, LLC; said in a statement. “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 submission for approval is based on early results in the monotherapy arm of the Phase I CHRYSALIS study (NCT02609776), a multi-center, open-label, multi-cohort study of amivantamab’s safety and efficacy in advanced NSCLC patients both as a monotherapy and in combination with lazertinib, a novel third-generation EGFR tyrosine kinase inhibitor (TKI).

The data, which were presented a poster presentation at the American Society of Clinical Oncology (ASCO) Virtual Scientific Program in May, found that patients in the monotherapy cohort saw a 36% overall response rate, and patients who had previously undergone platinum-based chemotherapy saw a 41% response rate.2

Data from the Phase I trial also support the establishment of an expanded access program (NCT04599712) that makes some patients eligible for amivantamab treatment ahead of the approval while the FDA reviews the BLA.

“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,” Mathai Mammen, MD, PhD; global head, Janssen Research & Development, Johnson & Johnson, said. “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.”

References

1. Janssen Submits Application to U.S. FDA Seeking Approval of Amivantamab for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. News release. Janssen Pharmaceutical Companies of Johnson & Johnson; December 3, 2020. Accessed December 4, 2020. https://www.janssen.com/janssen-submits-application-us-fda-seeking-approval-amivantamab-treatment-patients-metastatic-non

2. Janssen Announces Phase 1 Results for Bispecific Antibody Amivantamab in the Treatment of Patients with Advanced Non-Small Cell Lung Cancer Harboring Exon 20 Insertion Mutations. News release. Janssen Pharmaceutical Companies of Johnson & Johnson; May 18, 2020. Accessed December 4, 2020. https://www.janssen.com/janssen-announces-phase-1-results-bispecific-antibody-amivantamab-treatment-patients-advanced-non