The Janssen Pharmaceutical Companies of Johnson & Johnson has reported that its Rybrevant (amivantamab-vmjw) demonstrated anti-tumour activity in non-small cell lung cancer (NSCLC) patients with mesenchymal-epithelial transition (MET) exon 14 skipping (METex14) mutations in a Phase I CHRYSALIS clinical trial.

A fully human, bispecific antibody, Rybrevant is designed to target epidermal growth factor receptor (EGFR) and MET receptors.

The open-label, multi-centre, first-in-human trial assessed the safety, pharmacokinetics and preliminary efficacy of Rybrevant as a single agent and in combinations with lazertinib in adult subjects with advanced NSCLC.

The trial has two parts, a Rybrevant monotherapy and combination-dose escalations part and Rybrevant monotherapy and combination-dose expansions part.

According to the initial results from the trial, the drug’s safety profile was in line with already reported experience when given at the approved Phase II dose of 1,050mg or 1,400mg.

The METex14 cohort of the Phase I trial had 19 subjects receiving an intravenous dose of Rybrevant.

The primary goal of the trial was disease response assessed using overall response rate (ORR).

Findings showed partial responses in 64% of the 14 response-evaluable subjects with confirmation pending in four participants.

In addition, activity was noted in treatment-naïve and already-treated subjects, including four of seven subjects who received prior MET tyrosine kinase inhibitor (TKIs) treatment.

The median time to first response was 4.1 months.

Data also revealed that most of the treatment-related adverse events (AEs) were of Grade 1-2, Janssen said.

Nearly 16% of the subjects reported treatment-related Grade ≥3 AEs, including dyspnea, hypoalbuminemia and rash.

In May 2021, the US Food and Drug Administration (FDA) granted approval to Rybrevant for the treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

The FDA approval was based on results demonstrating an ORR of 40% and a median duration of response of 11.1 months.

Janssen Research & Development Solid Tumors Clinical Development vice-president Kiran Patel said: “While the recent FDA approval of Rybrevant was an important milestone for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations, there continues to be a lack of long-term treatment options for patients with other mutations, including MET exon 14 skipping mutations.

“We are encouraged by these data showing evidence that Rybrevant can lead to broad activity against both EGFR and MET-driven tumours.”