Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy

Abstract

Objective: This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation. Data Synthesis: The literature search to identify clinical trials returned only the CHRYSALIS phase 1 study. In a phase I trial, amivantamab-vmjw was associated with an overall response rate (ORR) of 40% (95% CI, 29–51) in the EGFR exon20ins NSCLC patient population (n = 81) after platinum-based chemotherapy. There were 3 complete responses (CRs) and 29 partial responses (PRs). The median duration of response (DOR) was 11.1 months (95% CI, 6.9—not reached; NR). The median progression-free survival (PFS) was 8.3 months (95% CI, 6.5–10.9), and overall survival (OS) was 22.8 months (95% CI, 14.6—NR). Application to Clinical Practice: This review summarizes the pharmacology, clinical evidence, and use of amivantamab-vmjw for patients with locally advanced or metastatic NSCLC with EGFR exon20ins mutation. Conclusion: The FDA approval of amivantamab-vmjw, the first bispecific antibody to target the exon20ins mutation, represents an important advancement in the treatment of patients with NSCLC with limited effective treatment options. The initial findings of the CHRYSALIS trial demonstrate an overall tumor response benefit with an acceptable safety profile.

Long-term survival after stereotactic body radiotherapy combined with immunotherapy plus anti-angiogenesis therapy in patients with advanced non-small cell lung cancer and EGFR exon 20 insertion mutation: a report of two cases

“…With the appearance of two EGFR ex20ins inhibitors (mobocertinib and amivantamab), new hope has been given to patients with EGFR ex20ins NSCLC. Clinical study results indicated amivantamab to be effective in 40% of patients with lung cancer who have failed platinum chemotherapy, with a median PFS of 8.3 months and a median overall survival of 22.8 months ( 23 , 24 ). Mobocertinib received accelerated United States Food and Drug Administration (FDA) approval on September 15, 2021, for the treatment of locally advanced or metastatic adult NSCLC for patients with the EGFR ex20ins mutation ( 25 , 26 ).…”

Engineering hydrophobicity and manufacturability for optimized biparatopic antibody–drug conjugates targeting c-MET

“…9 Amongst those, early monovalent and bivalent mAb approaches relied on antagonism and antibody-dependent cellular cytotoxicity (ADCC) as the main modes of action and failed in clinical development. 10–12 Next-generation biologics were designed as bispecific antibodies, such as amivantamab 13 or MM-131, 14 or focused on target degradation. 15–17 One molecular mechanism for effective target degradation is crosslinking of more than two target molecules via dual binding of suitable combinations of paratopes and their optimal orientation in a biparatopic antibody to favor inter- over intra-molecular binding ( Figure 1a ).…”

The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation

“…Amivantamab (JNJ-61186372) (7,15,(25)(26)(27) is a bispecific antibody targeting EGFR and MET, exhibiting immune celldirected activity. Due to its promising efficacy and safety profile, on May 21, 2021, the United States Food and Drug Administration (FDA) granted approval for its use in the treatment of EGFR-exon20ins in platinum-based chemotherapy-experienced or treatment-naïve patients with metastatic NSCLC (28,29).…”