Johnson & Johnson's EGFR-MET Bispecific Antibody Amivantamab and Third-Generation EGFR-TKI Lazertinib Receive Four IND Approvals in China for NSCLC

Reposted from | Medical Horizon

According to the latest public announcement made today by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration, the combination therapy of amivantamab injection, an EGFR-MET bispecific antibody, and lazertinib tablets, a third-generation EGFR-TKI, both under Johnson & Johnson, has received implied approval for four clinical trials. The indications are as follows:

• Amivantamab Injection/Lazertinib Tablets Combination Therapy for the Treatment of Patients with Non-Small Cell Lung Cancer (NSCLC) Harboring EGFR Exon 19 Deletion or L858R Activating Mutations Who Have Experienced Disease Progression Following First-Line Treatment with First- or Second-Generation TKIs, or Following First- or Second-Line Treatment with Third-Generation TKIs (e.g., Osimertinib).
• Amivantamab injection/lazertinib tablets combination therapy is indicated for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R activating mutations, whose disease has progressed following treatment with osimertinib or other approved third-generation EGFR TKIs, as well as platinum-based doublet chemotherapy.

It is worth noting that both of the aforementioned drugs are investigational agents co-developed by Johnson & Johnson with partners through licensing agreements, and have currently become key development projects in the company’s oncology R&D portfolio. Among them, amivantamab was granted Breakthrough Therapy Designation by the U.S. FDA in March this year; Lazertinib tablets were licensed in by Janssen, a subsidiary of Johnson & Johnson, in 2018 for over $1.25 billion.

Image source: Screenshot from the CDE official website

Amivantamab (code name: JNJ-6372) is a bispecific antibody targeting EGFR and MET. It not only blocks the binding of ligands to EGFR and MET and promotes receptor degradation, but also triggers antibody-dependent cellular cytotoxicity (ADCC). This antibody was jointly developed by Janssen and Genmab using Genmab’s DuoBody technology platform. In March this year, the U.S. FDA granted breakthrough therapy designation to this drug for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. Reportedly, clinical trials of this innovative therapy in this therapeutic area have yielded positive results, and it is expected that a regulatory application will be submitted in the United States before the end of this year.

Lazertinib is a highly potent, oral, irreversible third-generation tyrosine kinase inhibitor (TKI) being developed for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR gene mutations. It reportedly exhibits high specificity for EGFR with specific activating mutations and is capable of crossing the blood-brain barrier. In 2018, Janssen, a subsidiary of Johnson & Johnson, acquired exclusive global rights to the drug outside of South Korea from a South Korean pharmaceutical company, with an upfront payment of $50 million and potential development and commercialization milestone payments totaling up to $1.205 billion.

Results from the Phase 1/2 clinical trial presented at the 2018 ASCO Annual Meeting demonstrated that lazertinib achieved an objective response rate (ORR) of 61% in patients with NSCLC who had developed resistance to EGFR-TKIs, and an intracranial ORR of 55% in patients with brain metastases.

As is well known, lung cancer is the leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. About 75% of NSCLC patients are diagnosed at an advanced stage, with a five-year survival rate of only 5%. Publicly available data indicate that EGFR mutations occur in 10%–35% of NSCLC cases globally, whereas approximately 50% of NSCLC patients in China harbor EGFR gene mutations.

For this very reason, many global efforts in the development of targeted therapies for lung cancer have sought to suppress tumor growth by inhibiting the activity of mutant EGFR. Over the past years, multiple generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), from first- to third-generation agents, have been approved for clinical use, bringing significant clinical benefits to many patients. However, the emergence of acquired resistance in patients treated with TKIs has led to continued disease progression.

To address drug resistance emerging during patient treatment, scientists in the pharmaceutical R&D community are continuously striving to develop new drugs, including the bispecific antibody amivantamab and the third-generation EGFR TKI lazertinib, which are being co-developed by Johnson & Johnson. The approval of the combination therapy of these two drugs for clinical trials in China marks another milestone in their clinical development process.

Notably, in July this year, Johnson & Johnson registered a Phase 3 clinical trial on ClinicalTrials.gov evaluating amivantamab in combination with lazertinib as first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations. The study aims to assess the efficacy and safety of this combination therapy compared to osimertinib or monotherapy as first-line treatment for EGFR-mutated (exon 19 deletion or exon 21 L858R substitution) locally advanced or metastatic NSCLC. According to publicly available information, the study plans to enroll 1,000 participants and will officially commence patient recruitment in October this year.

The approval of the clinical trial application for the combination therapy of amivantamab injection and lazertinib tablets in China signifies that this investigational combination regimen is poised to initiate relevant clinical studies in the country. We congratulate Johnson & Johnson and hope that these studies proceed smoothly, bringing new therapeutic hope to patients at the earliest possible date.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Sep 15, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=25#

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