The Janssen Pharmaceutical, a Johnson & Johnson company, reported the U.S. Food and Drug Administration (FDA) granted its JNJ-6372 Breakthrough Therapy Designation. The drug is being developed for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations where the disease has progressed while the patient is on or after receiving platinum-based chemotherapy.
Breakthrough Therapy Designation is designed to speed the development and regulatory review of drugs for serious or life-threatening diseases. It is based on preliminary clinical data showing the drug might have substantial improvement on at least one clinically significant endpoint over available therapy.
NSCLC and EGFR Exon 20 insertion mutation cancers do not typically respond to EGFR tyrosine kinase inhibitors (TKI)s and have a worse prognosis compared to patients with more common EGFR mutations.
JNJ-6372 is an EGFR-MET bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications. It came out of a licensing deal with Genmab for use of its DuoBody technology platform. Janssen also collaborated with Genmab on its Darzalex (daratumumab), a blockbuster drug for multiple myeloma, and its follow-up HexaBody-CD38.
The Breakthrough Therapy Designation is based on data from a Phase I trial of JNJ-6372 alone and in combination with lazertinib, a novel third-generation EGFR TKI in adults with advanced NSCLC. Currently the company is enrolling Part 2 dose expansion cohorts as the study is now evaluating the drug as a monotherapy in multiple NSCLC sub-populations with specific genetic changes like those with C797S resistance mutation or MET amplification. Lazertinib is a third-generation EGFR inhibitor that Janssen licensed from Korea’s Yuhan Corp in 2018 for $50 million up front and up to $1.25 billion in possible milestone payments.
“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, Global Therapeutic Area Head, Oncology, Janssen Research & Development. “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.”
EGFR exon 20 insertions have been reported in 4% to 10% of all cases of EGFR-mutated NSCLC, as well as in other cancers including a rare head and neck cancer called sinonasal squamous cell carcinoma (SNSCC).
These types of mutated cancers do not typically respond to treatment with first- and second-generation EGFR inhibitors like AstraZeneca’s Iressa (gefitinib), Roche’s Tarceva (erlotinib) and Boehringer Ingelheim’s Giotrif (afatinib). They also do not seem to respond to immunotherapies like checkpoint inhibitors.
In 2019, Spectrum Pharmaceuticals provided data for its third-generation therapy poziotinib in EGFR exon 20 insertion mutation-positive NSCLCs but did not receive Breakthrough Therapy Designation from the FDA. The company expects to report more data from a Phase II trial in 2022.
Lung cancer is the second most common cancer in men and women in the U.S., after skin cancer. NSCLC accounts for 80% to 85% of all lung cancers. The primary subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.