Janssen Announces Positive Clinical Results for Rybrevant (amivantamab-vmjw) in NSCLC Patients with MET Exon 14 Skipping Mutations

On August 19, 2021, Janssen, a subsidiary of Johnson & Johnson, announced preliminary data from the Phase 1 CHRYSALIS clinical trial. The trial aimed to evaluate its EGFR/MET bispecific antibody therapy, Rybrevant (amivantamab-vmjw), for the treatment of patients with non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) gene exon 14 skipping (METex14) mutations. Initial data from the trial demonstrated that Rybrevant exhibited positive anti-tumor activity in patients with METex14 mutations. The safety profile was consistent with studies conducted at the dose approved for Phase 2 clinical trials.

Rybrevant is a humanized EGFR/MET bispecific antibody. It exerts multiple anticancer mechanisms of action, not only blocking EGFR- and MET-mediated signaling but also directing immune cells to target tumors harboring activating and resistance-conferring EGFR/MET mutations and amplifications. The drug received accelerated approval from the U.S. FDA in May this year, becoming the first precision therapy for patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.

In China, this bispecific antibody therapy has been granted breakthrough therapy designation by the National Medical Products Administration (NMPA) and is currently being evaluated in multiple clinical trials in the country, including a combination regimen with the third-generation EGFR tyrosine kinase inhibitor lazertinib for the first-line treatment of locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations.

NSCLC accounts for 80%–85% of all lung cancers, with approximately 3% of patients harboring the METex14 mutation. This mutation leads to overactivation of the MET receptor, promoting the growth of the corresponding cancer cells. Furthermore, the vast majority of patients develop resistance to MET tyrosine kinase inhibitor (TKI) therapy, necessitating new treatment options.

In the CHRYSALIS trial, 19 NSCLC patients with MET exon 14 skipping mutations received treatment with Rybrevant. The primary endpoint of the trial was the overall response rate (ORR). Trial results showed that among 14 evaluable patients, 64% achieved a partial response. Furthermore, antitumor activity was observed in both treatment-naïve and previously treated patients, including 4 patients (n=4/7) who had previously received TKI therapy.

In terms of safety, most treatment-related adverse events (AEs) were grade 1–2. During the trial, treatment-related AEs of grade ≥3 were observed in 3 patients (16%), including dyspnea (n=1), hypoalbuminemia (n=1), and rash (n=1). The incidence of treatment-related AEs leading to dose reduction and treatment discontinuation was 11% and 5%, respectively. A single dose interruption occurred in 32% of patients.

References:

[1] Janssen Presents Phase 1 Results for Rybrevant™ (amivantamab-vmjw) in the Treatment of Patients with Advanced Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutations. Retrieved August 19, 2021, from https://www.prnewswire.com/news-releases/janssen-presents-phase-1-results-for-rybrevant-amivantamab-vmjw-in-the-treatment-of-patients-with-advanced-non-small-cell-lung-cancer-with-met-exon-14-skipping-mutations-301358879.html

(Original text abridged)

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