Janssen Launches Phase III Trial of Amivantamab in China and Submits BLA to FDA for First-Line NSCLC Treatment

On December 8, the Insight database showed that Johnson & Johnson initiated the first Phase III clinical trial in China for amivantamab, an EGFR/c-Met bispecific antibody, in combination with the third-generation EGFR inhibitor lazertinib as first-line treatment for advanced unresectable non-small cell lung cancer (NSCLC). This bispecific antibody has received “Breakthrough Therapy” designation in both China and the United States. Recently, Johnson & Johnson submitted a Biologics License Application (BLA) to the FDA.

Source: Insight Database (http://db.dxy.cn/v5/home/)

Source: CDE Official Website

Amivantamab (development code: JNJ-61186372) is an EGFR/c-Met bispecific antibody developed by Johnson & Johnson. In March this year, the drug received Breakthrough Therapy Designation from the FDA; in October, it again received Breakthrough Therapy Designation in China. Lazertinib, used in combination with Amivantamab, is also developed by Johnson & Johnson and is a third-generation EGFR small-molecule inhibitor. Currently, its highest development stage in China is Phase I clinical trials.

Prior to the initiation of the current Phase III clinical trial, Johnson & Johnson had already conducted a Phase I clinical trial in 2019 among patients with advanced non-small cell lung cancer (NSCLC) to assess safety, pharmacokinetics (PK), explore the recommended Phase II dose, and evaluate preliminary efficacy.

From: Insight Database (http://db.dxy.cn/v5/home/)

CTR20202472 is a parallel, randomized, double-blind, international, multicenter Phase III clinical trial with a target enrollment of 1,000 participants internationally and 200 participants in China. The trial is being conducted at 35 hospitals in China, with Dr. Lu Shun from Shanghai Chest Hospital serving as the principal investigator. Patient recruitment has not yet commenced.

The primary objective of this trial is to evaluate the efficacy of amivantamab in combination with lazertinib versus osimertinib (brand name: Tagrisso) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations (exon 19 deletions or exon 21 L858R substitutions). The primary endpoint is progression-free survival (PFS), with an estimated follow-up duration of 42 months. Secondary endpoints include overall survival (OS, with an estimated follow-up duration of 60 months), objective response rate (ORR), and duration of response (DOR), among others.

Furthermore, according to the Insight database, Johnson & Johnson has registered six clinical trials of Amivantamab on ClinicalTrials.gov, including two Phase III trials. In addition to combination therapy with Lazertinib, Johnson & Johnson has also explored the use of Amivantamab in combination with carboplatin/pemetrexed for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions.

Source: Insight Database (http://db.dxy.cn/v5/home/)

At the 2020 ASCO Annual Meeting, Johnson & Johnson announced the results of the Phase I CHRYSALIS study (NCT02609776). The data demonstrated that amivantamab treatment yielded durable responses in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. Among all evaluable patients, the overall response rate (ORR) was 36%, the median duration of response (DOR) was 10 months, and the clinical benefit rate (defined as ≥ partial response [PR] + stable disease for ≥12 weeks) was 67%. In the subset of evaluable patients who had previously received platinum-based chemotherapy, the ORR was 41%, the median DOR was 7 months, and the clinical benefit rate was 72%.

It is worth noting that no drugs targeting EGFR exon 20 mutations have been approved by the FDA to date; amivantamab is the first therapeutic agent approved for this patient population.