FDA Grants Breakthrough Therapy Designation to JNJ-6372 in Metastatic Non-Small Cell Lung Cancer

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for JNJ-6372 to Janssen Pharmaceutical, a Johnson & Johnson Company. NJ-6372 is an investigational treatment for metastatic non-small cell lung cancer (mNSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations. It has been approved for people whose disease continues to grow either during or after receiving platinum-based chemotherapy.^1-4

What is a “Breakthrough Therapy Designation”?

The FDA may grant Breakthrough Therapy Designation for a new drug that treats a serious or life-threatening condition. This designation is based on information from preliminary clinical trials. It can be issued if the research findings can demonstrate that the investigational drug offers improvement in at least one important outcome over currently available treatments. This allows drug development and FDA review to be fast-tracked for further investigation.^1,5

Non-small cell lung cancer and EGFR

Lung cancer is the second most common type of cancer in the US. There are several types of lung cancer and non-small cell is the type that makes up 80-85 percent of all lung cancers.^1,3 There are subtypes of NSCLC based on the pattern of the cancer cells. When the cancer is metastatic, it spreads beyond the lung.

One way in which non-small cell lung cancer develops is through a gene mutation known as epidermal growth factor receptor (EGFR). EGFR is a signal that promotes normal cell growth and change. In certain types of cancer, the EGFR mutates and causes cells to grow and divide abnormally.⁶ Another signal that can develop a mutation is called the Mesenchymal Epithelial Transition factor. If this mutation occurs with EGFR it can also lead to abnormal cell changes and can result in cancer.^1-4

Current treatment options

An EGFR mutation occurs in 10-15 percent of patients with non-small cell lung cancer.^1,3-4 The standard treatment for people with this mutation is platinum-based therapy chemotherapy. Platinum-based therapy works when the drugs are able to kill the cancer cells that divide and grow abnormally. Unfortunately, this can affect healthy cells as well.

Other treatments include tyrosine kinase inhibitors (TKIs).^1-4 TKIs try to destroy cancer cells by attacking the EGFR. This drug also works to stop the cancer cells from dividing and growing abnormally.⁷

How does JNJ-6372 work?

Some people with non-small cell lung cancer have very rare EGFR mutations. One of these is an “Exon 20 insertion mutation.” This is the part of the DNA that is changed in the cancer cells of this group of patients. People with this mutation typically do not respond as well to standard treatments. They have a poorer outcome when compared to patients with other mutations.^1,3

JNJ-6372 is a bispecific antibody. An antibody is a protein that finds foreign substances in the body and attacks them. JNJ-6372 is designed to specifically attack the Exon 20 insertion mutation. This blocks the EGFR and MET signals that can cause cancer to develop.⁴

What’s next for JNJ-6372?

The research of JNJ-6372 is ongoing as there are several parts to the trial. In the first phase of the trial, investigators were looking to see if the JNJ-6372 was safe; how the body uses and eliminates (gets rid of) the drug. JNJ-6372 received breakthrough therapy designation based on results from this first phase, first-in-human study. Phase 2 is currently enrolling participants. Investigators are looking to determine appropriate and safe dosing protocols. They will also continue to look to compare treatment effectiveness when combined with another drug, lazertinib, a tyrosine kinase inhibitor.²

Clinical trial eligibility requirements

Eligibility for future trial participants includes people diagnosed with metastatic non-small cell lung cancer with the EGFR Exon 20 mutation. Additionally, people must have a high level of function which includes having the ability to do things like light house or office work.

Not everyone with non-small cell lung cancer is eligible for the trial. Having certain other diseases or conditions, besides NSCLC, may affect treatment. Some others who may be excluded include people with cancer that has spread to the brain or have a history of another cancer within the prior three years.²

JNJ-6372 continues to be in clinical development to target this form of genetically-defined lung cancer.¹