Janssen Bags FDA Breakthrough Therapy Designation for Lung Cancer Drug

by Ruchi Jhonsa
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By Ruchi Jhonsa, Ph.D.

The FDA has granted breakthrough designation for Janssen Pharmaceuticals’ JNJ-6372 for treatment of patients with metastatic non-small cell lung cancer, which harbor epidermal growth receptor (EGFR) Exon 20 mutations. The breakthrough designation followed a Phase 1 clinical trial that evaluated drug safety, drug dose and preliminary efficacy, alone and in combination with lazertinib, a novel third-generation EGFR inhibitor in patients where the disease has progressed in or after receiving platinum-based chemotherapy. The drug alone or in combination will be particularly useful for treating NSCLC cases which harbor exon 20 insertions making them resistant to first and second-generation EGFR inhibitors like AstraZeneca’s gefitinib, Roche’s tarceva and Boehringer Ingelheim’s afatinib. While results from Phase 1 are coming, Janssen has already started gearing up for Phase 2 trial of JNJ-6372 monotherapy in multiple NSCLC sub-populations with specific genetic changes like those with C797S resistance mutation or MET amplification. Clearly, this news has boosted the company’s plans to enter the lucrative NSCLC market sooner than expected.

Immediately after the launch of the Phase 1 trial in 2016, Janssen struck a licensing deal for lazertinib with Yuhan Corporation, a South Korea based biotech firm. This was a win-win deal for both the companies as Yuhan received a whopping $50 million upfront and up to $1.25 billion in possible milestone payments and Janssen got the potential blockbuster drug. In the coming years, the two drugmakers decided to work together on global clinical trials evaluating lazertinib separately as well as in combination with Janssens’ bispecific drug.


The Genetic Makeup of EGFR-TKI Refractory NSCLC

In the early 2000s, a distinct observation was made in a small population of patients affected with non-small cell lung cancer-they responded extremely well to treatment with EGFR inhibitors. What was different in these patients from other NSCLC patients was the presence of EGFR activating mutations that constitutively activated EGFR, causing EGFR dependent cancer proliferation. It was reported that the patients whose tumors exhibit EGFR mutations showed a 75% response rate to EGFR inhibitors gefitinib and erlotinib. However, a few years later another set of EGFR activating mutations were discovered that failed to respond to first and second-generation EGFR inhibitors. These mutations, which account for 9% of all EGFR mutations, are a result of insertion in the exon 20 of the EGFR receptor.

EGFR exon 20 insertion mutations make up approximately 4-9% of all EGFR-mutated NSCLC. Although this would result in a very small patient population within NSCLC cases, it is nevertheless a very high unmet need area due to the lack of effective treatment options. Janssens’ drug, JNJ-6372 has been specifically designed to target activating and resistant exon 20 EGFR mutations and MET mutations and amplifications, thereby putting a stop on the growth of EGFR induced NSCLC. The drug was developed using a novel DuoBody technology platform, which was licensed from Genmab in 2012.


Growing Players in the NSCLC Market

Janssen is not the only player in this market. Despite its breakthrough designation, strong competition is expected from Nevada based Spectrum Pharmaceuticals which is working on testing poziotinib for NSCLC with EGFR exon 20 insertions. Although it failed to meet the primary endpoint of overall response rate, it still showed positive changes in disease control rate, duration of response and safety profile and is expected to report topline results in 2022. Takeda is also in line to claim the market with its TAK-788, an EGFR, and HER2 inhibitor. Phase II results for the drug showed significant improvement in the objective response rate and progression-free survival in this particular category of patients.

“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.”

Related Article: SCLC Treatment Gets a Boost as PharmaMar’s Lurbinectedin Bags Priority Review Status

  1. Vyse and Huang, 2019, Nature


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