Amivantamab/Chemotherapy ± Lazertinib Improves PFS in Pretreated EGFR+ NSCLC


Amivantamab-vmjw plus carboplatin and pemetrexed, administered with or without lazertinib, significantly improved progression-free survival vs chemotherapy alone in patients with locally advanced or metastatic non–small cell lung cancer with EGFR exon 19 deletions or L858R substitutions after progression on or after osimertinib.

Peter Lebowitz, MD, PhD

Peter Lebowitz, MD, PhD

Amivantamab-vmjw (Rybrevant) plus carboplatin and pemetrexed (Alimta), administered with or without lazertinib (Leclaza), significantly improved progression-free survival (PFS) vs chemotherapy alone in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitutions after progression on or after osimertinib (Tagrisso), according to topline data from the phase 3 MARIPOSA-2 trial (NCT04988295).1

The safety profile of the regimen was consistent with what has previously been reported with the combination.

The data, which will include information on secondary end points like overall survival (OS), objective response rate (ORR), duration of response (DOR), and intracranial PFS, will be submitted for presentation at an upcoming conference.

“MARIPOSA-2 provides the first phase 3 study data of [amivantamab]-based regimens in the broader EGFR-mutated non–small cell lung cancer population,” Peter Lebowitz, MD, PhD, global therapeutic area head, Oncology, Janssen Research & Development, LLC., stated in a news release. “The study builds on the significant innovation of [amivantamab], a first-in-class bispecific antibody targeting two major oncogenic driver pathways, with clinically meaningful results that may change the treatment paradigm.”

Currently, The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for Non–Small Cell Lung Cancer list amivantamab as a subsequent therapy option with a Category 2A recommendation for patients whose disease has progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation–positive advanced NSCLC.

Previously, the addition of amivantamab to lazertinib and chemotherapy demonstrated promising antitumor activity in previously treated patients with EGFR-mutant NSCLC in findings from the phase 1 CHRYSALIS-2 trial (NCT04077463).2

The randomized, open-label, phase 3 MARIPOSA-2 trial is evaluating the activity and safety of amivantamab plus chemotherapy with and without lazertinib in 657 patients with locally advanced or metastatic EGFR-mutant NSCLC following progression on or after osimertinib.1

To be eligible for enrollment, patients had to have at least 1 measurable lesion according to RECIST v1.1 criteria that had not been previously irradiated; histologically or cytologically confirmed locally advanced or metastatic, nonsquamous NSCLC with a documented EGFR exon 19 deletion or L858R substitution mutation; an ECOG performance status of 0 or 1; and resolution to grade 1 or baseline level of toxicity from prior anticancer therapy.

Notably, osimertinib could have been received in the first- or second-line setting after progression on a previous first- or second-generation EGFR TKI. Patients who received prior neoadjuvant or adjuvant therapy were eligible for enrollment if disease progression occurred at least 12 months after the last dose of therapy and patients experienced subsequent progression on osimertinib. Discontinuation of osimertinib at least 8 days before randomization was required.

Patients with a history or brain metastases were eligible so long as the lesions were treated as clinically indicated at least 14 days prior to randomization and no more than 10 mg of prednisone or an equivalent was required for intracranial disease management.

Eligible patients were randomly assigned to receive amivantamab plus chemotherapy and lazertinib; amivantamab plus chemotherapy; or chemotherapy alone. Treatment was administered for up to 4, 21-day cycles, after which patients continued amivantamab plus pemetrexed and lazertinib; pemetrexed; or amivantamab plus pemetrexed as maintenance therapy until disease progression.3

The dual primary end point was PFS per RECIST v1.1 criteria as assessed by blinded independent central review (BICR) in each experimental arm vs chemotherapy alone. Secondary end points included ORR as assessed by BICR, OS, DOR, time to subsequent therapy, PFS after first subsequent therapy (PFS2), and intracranial PFS, the latter of which was based on serial brain imaging.1

The combination of amivantamab and lazertinib is also being evaluated in the pivotal phase 3 MARIPOSA trial (NCT04487080), in which patients with newly diagnosed EGFR-mutated NSCLC will be randomly assigned to treatment with the combination therapy of amivantamab and lazertinib, osimertinib, or lazertinib alone.


  1. 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. Janssen. September 6, 2023. Accessed September 6, 2023.
  2. Marmarelis M, Lee SH, Spira AI, et al. Amivantamab and lazertinib in combination with platinum-based chemotherapy in relapsed/refractory EGFR-mutant NSCLC. Presented at: 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria; Abstract MA07.04.
  3. 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). Updated May 31, 2023. Accessed September 6, 2023.
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