Johnson & Johnson Announces Positive Phase 1 Results for Rybrevant (amivantamab) in METex14 Skipping Mutation-Positive Non-Small Cell Lung Cancer

Compiled & Translated by | Fan Dongdong

Recently, Johnson & Johnson announced preliminary data from the Phase 1 CHRYSALIS trial evaluating Rybrevant (amivantamab) in patients with non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition factor (MET) exon 14 skipping (METex14) mutations. The results demonstrated that the antitumor activity and safety profile of Rybrevant in patients with METex14 mutations were consistent with the outcomes observed using the previously approved dosing regimen from the Phase 2 CHRYSALIS trial (1,050 mg for patients weighing <80 kg and 1,400 mg for those weighing ≥80 kg).

Preliminary detailed results from this trial will be presented as an oral presentation at the 2021 World Conference on Lung Cancer (WCLC), hosted by the International Association for the Study of Lung Cancer (IASLC), from September 8 to 14. Statistics indicate that METex14 mutations occur in approximately 3% of patients with non-small cell lung cancer (NSCLC). These genetic alterations lead to MET receptor overactivation, driving corresponding cancer cell proliferation. Although MET inhibitors have recently received accelerated approval in certain countries and regions, the vast majority of patients ultimately develop resistance to these therapies, underscoring the continued clinical need for novel treatment options.

“Recent advances in the treatment of non-small cell lung cancer have provided benefits for patients with METex14 mutations; however, because these therapies are only effective for a limited duration, patients ultimately find themselves in need of new treatment options,” said Alexander Spira, MD, Co-Chair of the U.S. Thoracic Oncology Program and Principal Investigator. “We look forward to sharing the latest research findings on amivantamab, as preliminary trial results indicate that its novel mechanism of action may benefit individuals with this type of lung cancer.”

In the Phase 1 CHRYSALIS trial, 19 patients with METex14 mutations in the METex14 cohort received intravenous RYBREVANT at 1050 mg (for patients weighing <80 kg) or 1400 mg (for patients weighing ≥80 kg). According to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, the trial used the overall response rate (ORR) as the primary endpoint to assess disease response. Results demonstrated that among the 14 response-evaluable patients, a partial response was observed in 64% of patients, with 4 responses pending confirmation. Efficacy was observed in both treatment-naïve and previously treated patients, including 4 out of 7 patients who had previously received MET tyrosine kinase inhibitor (TKI) therapy.

The median time to first response was 4.1 months (range: 1.6 to 9.9). Most treatment-related adverse events (AEs) associated with amivantamab observed in the trial were Grade 1 or 2. Treatment-related Grade 3 AEs were observed in 3 patients (16%) and primarily included 1 case of dyspnea, 1 case of hypoalbuminemia, and 1 case of rash. The incidence of treatment-related AEs leading to dose reduction and discontinuation was 11% and 5%, respectively. Treatment interruption occurred in 32% of patients in the trial.

The active ingredient of Rybrevant is amivantamab, a fully human EGFR and mesenchymal-epithelial transition factor (MET) bispecific antibody with immune cell-engaging activity that targets tumors harboring activating and resistance-conferring EGFR and MET mutations and amplifications. In May this year, the U.S. Food and Drug Administration (FDA) approved Rybrevant for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. Notably, Rybrevant is the first targeted therapy to receive regulatory approval for the treatment of EGFR exon 20 insertion mutation-positive NSCLC.

The U.S. approval of Rybrevant was primarily based on a clinical trial involving 81 patients. Trial results showed that Rybrevant achieved an overall response rate of 40%, with a median duration of response of 11.1 months, and 63% of patients experienced a duration of response exceeding 6 months. Dr. Kiran Patel, Vice President of Clinical Development for Solid Tumors at Janssen Research & Development, stated that while the recent FDA approval of Rybrevant represents a significant milestone for patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, there remains a lack of therapeutic options for patients with other genetic mutations, including METex14. He noted that new data for Rybrevant demonstrate the therapy's broad activity against EGFR- and MET-driven tumors.

Previously, Rybrevant was granted breakthrough therapy designation by China's National Medical Products Administration (NMPA) and is currently undergoing multiple clinical trials in mainland China, including in combination with the third-generation EGFR tyrosine kinase inhibitor lazertinib for the first-line treatment of locally advanced or metastatic non-small cell lung cancer with EGFR mutations.

Reference: Janssen Presents Phase 1 Results for RYBREVANT (TM) (amivantamab-vmjw) in the Treatment of Patients with Advanced Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutations