MARIPOSA Trial to Examine How Amivantamab Plus Lazertinib Compares With Osimertinib in EGFR+ NSCLC

The MARIPOSA study seeks to assess efficacy, safety, and pharmacokinetics of the combination of amivantamab-vmjw and lazertinib in locally advanced, or metastatic non-small cell lung cancer.

An investigation of treatment with the combination of amivantamab-vmjw (Rybrevant) and lazertinib (Leclaza) compared to osimertinib (Tagrisso) patients with epidermal growth factor receptor (EGFR) mutation positive, locally advanced, or metastatic non-small cell lung cancer (NSCLC) is planned to launch.1

The MARIPOSA study (NCT04487080) seeks to assess the efficacy, safety, and pharmacokinetics of the investigational combination in 3 phases.

The most prevalent actionable driver mutations in NSCLC result in the activation of EGFR. While research has shown the third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib, to demonstrate positive results in terms of efficacy in patients with NSCLC caused by mutations in the EGFR, it has been reported that almost all patients eventually will relapse because of resistance to the treatment.

However, other studies have looked into amivantamab and lazertinib and shown that they sufficiently block the EGFR. The CHRYSALIS study (NCT02609776) was designed to examine the combination of amivantamab and lazertinib further.

Previously reported findings from the CHRYSALIS trial led to the accelerated approval of amivantamab by the FDA on May 21, 2021, for the treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.2 The FDA also granted approval to the Oncomine Dx Target Test as a companion diagnostic for amivantamab.

When this combination was used concurrently, lung tumors were seen to shrink in patients whose lung cancer had not been previously treated. Antitumor activity in the treatment-naive and osimertinib-relapsed setting was also demonstrated.

To investigate treatment with amivantamab and lazertinib versus osimertinib, placebo, and lazertinib in the frontline setting of EGFR-mutant NSCLC, the multicenter, randomized, MARIPOSA trial will enroll 1,000 patients with newly-diagnosed locally advanced or metastatic NSCLC. Participants were randomly assigned 2:2:1 within 3 experimental arms, separating patients by mutation type, race (Asian vs non-Asian), and history of brain metastases (present vs absent).

Patients in the open-label experimental combination arm will receive amivantamab at 1050 mg intravenously once a week for the first 4 weeks and every 2 weeks if their body weight is less than 80 kg and 1400 mg if their body weight is greater than 80 kg. Amivantamab will be administered for 28 cycles. They were also given lazertinib orally once a day at 240 mg. In the double-blinded comparator arm, patients will be treated with osimertinib 80 mg with matching placebo and lazertinib 240 mg orally once daily. Finally, in the double-blinded experimental arm, patients will receive lazertinib plus placebo, and osimertinib at matching dose levels and schedules.

In order to be eligible in the study, participants were required to be 18 years of age or older, will have locally advanced or metastatic EGFR-mutant NSCLC which cannot be fixed curative therapy, and have a tumor that harbors exon 19 deletions or exon 21 L858R substitution. Additionally, they must have at least 1 measurable lesion, according RECIST v1.1, and submission of unstained tissue from tumor was also required for individuals to participate in the study.

Progression-free survival (PFS) per blinded independent central review according to RECIST v1.1 is the primary end point of the study. Secondary end points include overall survival, objective response rate, duration of response, PFS after first subsequent therapy, time to symptomatic progression, and intracranial PFS.

The trial is actively recruiting individuals who meet the key criteria at 321 locations across the United States, South America, Europe, and Asia, and the Middle East. The trial is expected to reach primary completion in April 2024.

REFERENCES:
1. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). ClinicalTrials.gov. Accessed February 24, 2022. https://bit.ly/3t6em5C
2. FDA grants accelerated approval to amivantamab-vmjw for metastatic non-small cell lung cancer. News release. FDA. May 21, 2021. Accessed February 24, 2022. https://bit.ly/3EZbJrb