▎WuXi AppTec Content Team Report

Screenshot source: CDE official website

Amivantamab (trade name in English: Rybrevant) is a product of Johnson & Johnson.Johnson & Johnson Innovative MedicineDevelopedA bispecific antibody under research that targets EGFR and MET. In addition to blocking EGFR and MET-mediated signal transduction, it can also guide immune cells to target activating and resistantEGFR/METTumors with Mutations and Amplifications。

In March 2020, the US FDA granted amivantamabBreakthrough Therapy Designation, for the treatment of specific NSCLC patients.In May 2021, the product received formal FDA approval., for the treatment of progression during or after platinum-based chemotherapyEGFRExon20Insertion mutation NSCLC patients. In August 2023, the product was also submitted to the FDA.Submitted a Supplemental Biologics License Application (sBLA), Used in combination with chemotherapy as a first-line treatment for patients carryingEGFRExon20Patients with locally advanced or metastatic NSCLC with insertional mutations.

In China, Amivantamab was included by the CDEBreakthrough Therapy Drug, for the treatment of progression during or after platinum-based doublet chemotherapy, or intolerance to platinum-based chemotherapyEGFR 20Patients with metastatic or surgically unresectable NSCLC harboring exon insertion mutations. According to the China Drug Clinical Trial Registration and Information Disclosure Platform,Currently, the product is undergoing multiple clinical trials., including treatmentEGFRMutant NSCLCPhase 3 Trial in Patients with Advanced or MetastaticSolid Tumor(IncludingEGFRPhase 2 trial for patients with mutant non-small cell lung cancer, treating advanced or metastaticColorectal CancerPhase 1b/2 trial for subjects, etc.

Since 2023, Amivantamab has achieved positive results in multiple clinical trials.

• PAPILLONIs a randomized, open-label Phase 3 study aimed atNew DiagnosisEGFRExon20Insertion Mutation in Advanced or Metastatic NSCLCIn patients, evaluate the efficacy and safety of amivantamab combined with chemotherapy compared to chemotherapy alone.The study achievedProgression-Free Survival (PFS) assessed by the Blinded Independent Central Review Committee (BICR)Primary EndpointPatients receiving amivantamab combined with chemotherapy compared to those receiving chemotherapy alone,PFSSignificant improvements with both statistical and clinical significanceThe safety of the combination therapy is consistent with that of the individual treatment regimens.

• MARIPOSA-2Is an open-label, randomized Phase 3 trial designed to evaluate in EGFR-Locally advanced or metastatic disease with progression during or after TKI osimertinib treatmentEGFR ex19delOrL858RMutant NSCLCAmong the patients,Evaluate the efficacy and safety of two regimens: amivantamab (with and without oral TKI product lazertinib) and chemotherapy.The trial met both primary endpoints, with amivantamab + chemotherapy reducing the risk of disease progression or death by 52% compared to chemotherapy alone; amivantamab + chemotherapy + lazertinib reducing the risk of disease progression or death by 56% compared to chemotherapy alone.Improvement in PFS was consistent across all predefined patient subgroups.

• MARIPOSAIt is a randomized, open-label Phase 3 trial,The purpose is toEGFRExon19Missing (ex19del`) or alternative mutations in locally advanced or metastatic NSCLC`Among the patients,Evaluate the efficacy of amivantamab combined with lazertinib compared to first-line treatment with osimertinib and lazertinib monotherapy.The trial met the primary endpoint., compared with the active control group, patients receiving Amivantamab combination therapyProgression-Free Survival Shows Statistically and Clinically Significant Improvement. The pre-specified interim overall survival (OS) analysis showed that, compared with the active control group,AmivantamabCombined therapy showed a trend of being beneficial to patients.

References:

[2]Treatment with RYBREVANT® (amivantamab-vmjw) Plus Chemotherapy Resulted in Statistically Significant and Clinically Meaningful Improvement in Progression-Free Survival in Patients with Newly Diagnosed EGFR Exon 20 Insertion Mutation-Positive Non-Small Cel.Retrieved Jul 17，2023, From https://www.janssen.com/treatment-rybrevant-amivantamab-vmjw-plus-chemotherapy-resulted-statistically-significant-and

[3]Phase 3 MARIPOSA-2 Study Shows RYBREVANT® (amivantamab-vmjw) Plus Chemotherapy Given with or without Lazertinib Reduced Risk of Disease Progression or Death by 56 and 52 Percent Respectively in Patients with EGFR-Mutated Non-Small Cell Lung Cancer who Progressed on or after Osimertinib. Retrieved October 23, 2023 from https://www.jnj.com/phase-3-mariposa-2-study-shows-rybrevant-amivantamab-vmjw-plus-chemotherapy-given-with-or-without-lazertinib-reduced-risk-of-disease-progression-or-death-by-56-and-52-percent-respectively-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-who-progressed-on-or-after-osimertinib 

[4]Landmark Phase 3 MARIPOSA Study Meets Primary Endpoint Resulting in Statistically Significant and Clinically Meaningful Improvement in Progression-Free Survival for RYBREVANT® (amivantamab-vmjw) plus Lazertinib Versus Osimertinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer. Retrieved September 28, 2023 from https://www.prnewswire.com/news-releases/landmark-phase-3-mariposa-study-meets-primary-endpoint-resulting-in-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-for-rybrevant-amivantamab-vmjw-plus-lazertinib-versus-osimertinib--301941646.html