2021-08-20| Trials & Approvals

J&J’s FDA-Approved Bispecific Antibody Registers Promising Phase 1 Results for a Different Indication

by Judy Ya-Hsuan Lin
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Non-small cell lung cancer (NSCLC) accounts for 84% of all lung cancer diagnoses. In particular, NSCLC with mesenchymal-epithelial transition exon 14 (METex14) skipping mutations is difficult to manage. MET inhibitors are used to reduce the hyperactivation of MET receptors and prevent cancer cell growth. However, a vast majority of patients eventually become resistant to the therapy.

On August 19th, J&J announced preliminary data from the Phase 1 CHRYSALIS study that evaluated its bispecific antibody, Rybrevant (amivantamab-vmjw) for the treatment of patients with NSCLC with METex14 skipping mutations. Results showed that the drug demonstrated anti-tumor activity in patients and a safety profile consistent with the previous dose used in Phase 2.

“Newer treatment advances for non-small cell lung cancer provide benefit to patients with MET exon 14 skipping mutations, but because they are effective for only a finite period of time, patients ultimately find themselves in need of new therapies,” said Alexander Spira, M.D., Ph.D., FACP, Director of the Virginia Cancer Specialists Research Institute, Co-Chair U.S. Oncology Thoracic Program and presenting study investigator.

The detailed results will be presented at the virtual meeting of the International Association for the Study of Lung Cancer’s (IASLC) 2021 World Conference on Lung Cancer (WCLC).


Phase 1 CHRYSALIS Study

A total of 19 patients with METex14 genetic variant participated in the Phase 1 CHRYSALIS study and received the same amount of dosage based on the individual’s weight as in the Phase 2 CHRYSALIS study.

The primary endpoint was the overall response rate (ORR). Of the 14 response evaluable enrollees, partial responses were observed in 64% with four patients pending confirmation. The activity was observed in untreated and previously-treated patients, including four of seven patients previously treated with MET tyrosine kinase inhibitors (TKIs). The median time to first response was 4.1 months.

The treatment-related adverse events were mostly in Grade 1-2. Grade 3 or above were observed in three patients, or 16% of the total sample population, which included dyspnea (N=1), hypoalbuminemia (N=1), and rash (N=1). 11% and 5% of patients’ adverse events led to dose reduction and discontinuation, respectively. 32% experienced dose interruptions.


Rybrevant’s Wide Usage to Multiple Types of Mutations of NSCLC

Rybrevant is a fully-human bispecific antibody directed against EGFR and MET receptors. Its largest potential competitor is Takeda’s small molecule drug, mobocertinib which has a PDUFA target action date of October 26th.

In several other clinical trials, Rybrevant has been examined to treat possible types of mutations of NSCLC, including

  1. Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations,
  2. Untreated advanced EGFR-mutated NSCLC in combination with EGFR inhibitor Lazertinib in the Phase 3 MARIPOSA study,
  3. Advanced or metastatic EGFR mutated NSCLC and exon 20 insertion mutations in combination with carboplatin-pemetrexed in the Phase 3 PAPILLON study.

Among the three studies, the first has already been approved by the FDA since May 2021 and filed regulatory submissions to health authorities in Europe and other markets.

Apart from testing the effectiveness of Rybrevant, there are studies investigating the feasibility of its subcutaneous administration based on safety and pharmacokinetics in the Phase 1 PALOMA study.

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