Phase 3 Study Demonstrates Amivantamab-vmjw is Safe, Effective in Improving PFS in Patients With NSCLC

The phase 3 MARIPOSA-2 study (NCT04988295) met its dual primary endpoints, demonstrating both statistically significant and clinically meaningful improvements in progression-free survival (PFS) versus chemotherapy alone, according to study investigators. The study assessed the efficacy and safety of amivantamab-vmjw (Rybrevant; Janssen), a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition with immune cell-directing activity. Amivantamab is given with and without lazertinib (Leclaza; Janssen) and combined with chemotherapy (carboplatin and pemetrexed) and without chemotherapy in participants with locally advanced or metastatic EGFR Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after failure on osimertinib (Tagrisso; AstraZeneca). MARIPOSA-2 is the first phase 3 study to show statistically significant and clinically meaningful improvement in PFS in the post-osimertinib setting.^1,2

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Amivantamab was granted accelerated approval by the FDA in May 2021 based on the overall response rate and duration of response (DoR). The therapy is approved for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed either on or after platinum-based chemotherapy.¹

The phase 3 trial is a randomized, open-label study evaluating the efficacy and safety of 2 treatments, amivantamab with and without lazertinib—an oral, third-generation, brain penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR—and chemotherapy. A total of 657 enrolled patients were randomized to receive treatment with amivantamab plus chemotherapy, amivantamab without chemotherapy, or chemotherapy alone. The dual primary endpoint was used to compare the PFS as assessed by blinded independent central review (BICR) for each experimental arm to chemotherapy alone. Secondary endpoints included objective response as assessed by BICR, overall survival, DoR, time to subsequent therapy, PFS after the first subsequent therapy, and intracranial PFS.¹

All study participants underwent serial brain imaging to allow for the assessments of intracranial endpoints and the central nervous system activity of amivantamab with and without lazertinib. This component of the study provides critical information because the brain metastases can lead to substantial burden and poor outcomes for patients.¹

"MARIPOSA-2 provides the first phase 3 study data of [amivantamab]-based regimens in the broader EGFR-mutated [NSCLC] population," said Peter Lebowitz, MD, PhD, global therapeutic area head of oncology at Janssen Research & Development, in a press release. "The study builds on the significant innovation of [amivantamab], a first-in-class bispecific antibody targeting 2 major oncogenic driver pathways, with clinically meaningful results that may change the treatment paradigm."¹

These findings, which Janssen plans to submit for presentation at an upcoming scientific congress, add to the evidence supporting the use of amivantamab in EGFR-mutated NSCLC. A combination of amivantamab and lazertinib is also being evaluated in a first-line setting for patients with EGFR-mutated NSCLC in the phase 3 MARIPOSA trial. To assess the contribution of components, this trial compares the combination therapy of amivantamab and lazertinib head-to-head with osimertinib, as well as a third arm of lazertinib.¹

Reference

1. Janssen. Phase 3 MARIPOSA-2 Study Meets Dual Primary Endpoint Resulting in Statistically Significant and Clinically Meaningful Improvement in Progression-Free Survival for RYBREVANT® (amivantamab-vmjw) Plus Chemotherapy With and Without Lazertinib versus Chemotherapy Alone in Patients with EGFR-Mutated Non-Small Cell Lung Cancer after Disease Progression on Osimertinib. News release. September 6, 2023. Accessed September 6, 2023. https://prn.to/480Hn6d

2. A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). ClinicalTrials.gov identifier: NCT04988295. Updated May 31, 2023. Accessed September 6, 2023. https://bit.ly/45DCKgX