It has been announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for JNJ-61186372 (JNJ-6372) 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. 

JNJ-6372 is an EGFR-mesenchymal epithelial transition factor (MET) bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications.

Currently, there are no FDA-approved targeted therapies for patients with lung cancer who have EGFR Exon 20 insertion mutations.

Patients with NSCLC and EGFR Exon 20 insertion mutations have a form of disease that is generally insensitive to EGFR tyrosine kinase inhibitor (TKI) treatments and carries a worse prognosis compared to patients with more common EGFR mutations (Exon 19 deletions/L858R substitution).

The current standard of care for this patient population is conventional cytotoxic chemotherapy.

“JNJ-6372 is a novel bispecific antibody that we believe has the potential to benefit patients with Exon 20 mutation insertions who often do not respond to currently available oral EGFR-targeted or immune checkpoint inhibitor therapies,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “This Breakthrough Therapy Designation is a significant milestone in our ongoing efforts to advance JNJ-6372 in clinical development and target genetically-defined lung cancer.”

The Breakthrough Therapy Designation is supported by data from a Phase 1, first-in-human, open-label, multi centre study (NCT02609776).

The study evaluates the safety, pharmacokinetics and preliminary efficacy of JNJ-6372 monotherapy and in combination with lazertinib, a novel third-generation EGFR TKI, in adult patients with advanced NSCLC.

The study seeks to determine the recommended Phase 2 dose in patients with advanced NSCLC.

Enrollment into the Part 2 dose expansion cohorts is ongoing, as the study evaluates JNJ-6372 monotherapy activity in multiple NSCLC sub-populations with genomic alterations such as those with C797S resistance mutation or MET amplification.

A U.S. FDA Breakthrough Therapy Designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.

The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

Source: Janssen