Janssen Announces Positive Phase 1 Results of EGFR-MET Bispecific Antibody Amivantamab in Refractory Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

Compiled by Fan Dongdong

Recently, Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, announced the results of the Phase 1 CHRYSALIS study (NCT02609776), which evaluated the efficacy of amivantamab (JNJ-6372) in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations. The results demonstrated that amivantamab exhibits potent and durable efficacy in NSCLC patients with EGFR exon 20 insertion mutations, with a manageable safety profile.

Amivantamab is an anti-EGFR-MET bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications. Researchers evaluated the efficacy of this therapy using overall response rate (ORR), duration of response, and safety profile, in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. These metrics also formed the basis for the therapy’s prior Breakthrough Therapy Designation by the U.S. FDA.

CHRYSALIS is an open-label, multicenter Phase 1 study evaluating the safety, pharmacokinetics, and efficacy of amivantamab as monotherapy and in combination with lazertinib, a novel third-generation EGFR tyrosine kinase inhibitor, in adult patients with advanced non-small cell lung cancer (NSCLC). Among 50 NSCLC patients with EGFR exon 20 insertion mutations who received two doses of amivantamab, 39 demonstrated an objective response. Detailed results will be presented at the ASCO Annual Meeting held at the end of the month.

The summary results showed that the overall response rate (ORR) for all patients was 36% (95% CI, 21–53), and among all patients who had received platinum-based chemotherapy, the ORR reached 41% (95% CI, 24–61). The median duration of response was 10 months for all evaluable patients and 7 months for those previously treated with platinum-based chemotherapy. The median progression-free survival (PFS) was 8.3 months (95% CI, 3.0–14.8) for all patients and 8.6 months (95% CI, 3.7–14.8) for patients who had received platinum-based chemotherapy. The clinical benefit rate (partial response or stable disease for at least 12 weeks) was 67% (95% CI, 50–81) for all patients and 72% (95% CI, 53–87) for those previously treated with platinum-based chemotherapy.

The most common adverse events (AEs) associated with this therapy were rash, infusion reactions, and paronychia. Infusion-related adverse reactions occurred primarily during the first infusion in patients, but these reactions did not preclude subsequent treatment. No Grade ≥3 rashes were reported; however, one patient experienced Grade 3 diarrhea. In the trial, 6% of patients experienced treatment-related serious adverse events, including cellulitis, interstitial lung disease, and shoulder or chest pain.

For patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, the disease is typically insensitive to currently approved EGFR tyrosine kinase inhibitors (TKIs). Consequently, these patients have a poorer prognosis compared to those with more common EGFR mutations (exon 19 deletions or L858R substitutions). The median overall survival for patients with advanced NSCLC and EGFR exon 20 insertion mutations is approximately 16 months. Currently, the FDA has not approved any targeted therapies specifically for lung cancer patients with EGFR exon 20 insertion mutations; therefore, the standard treatment regimen for this patient population remains conventional chemotherapy.

Dr. Kiran Patel, Vice President of Clinical Development for Solid Tumors at Janssen, stated, “Despite progress in the treatment of patients with lung cancer, there is still a need to develop new therapies for patients diagnosed with non-small cell lung cancer (NSCLC) harboring EGFR Exon 20 mutations. We are pleased to present the preliminary trial results of amivantamab.”

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Janssen Announces Phase 1 Results for Bispecific Antibody Amivantamab in the Treatment of Patients with Advanced Non-Small Cell Lung Cancer Harboring Exon 20 Insertion Mutations