Amivantamab Significantly Improves PFS Vs Chemotherapy in EGFR+ NSCLC

The FDA accepted a supplemental biologics license application for amivantamab plus chemotherapy as a treatment for patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations in August 2023.

Combining amivantamab-vmjw (Rybrevant) with chemotherapy produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs chemotherapy alone in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R substitutions, according to a press release on data from the phase 3 MARIPOSA-2 study (NCT04988295).¹

Investigators confirmed that amivantamab met the primary end point of PFS when administered with or without lazertinib (Leclaza). Additionally, investigators reported no new safety signals when adding amivantamab to chemotherapy in this patient population. Developers intend to present additional data—including those related to overall survival (OS), objective response rate (ORR), duration of response, and intracranial PFS—at a future scientific meeting.

“MARIPOSA-2 provides the first phase 3 study data of [amivantamab]-based regimens in the broader EGFR-mutated [NSCLC] population,” Peter Lebowitz, MD, PhD, global therapeutic area head of Oncology at Janssen Research & Development, LLC, said in the press 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.”

Investigators of the open-label randomized phase 3 MARIPOSA-2 trial are assessing patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitutions previously treated with osimertinib (Tagrisso) across 3 treatment arms. Patients were randomly assigned to receive amivantamab plus chemotherapy consisting of carboplatin and pemetrexed, amivantamab plus lazertinib and chemotherapy, or chemotherapy on its own.

The study’s primary end point is PFS as assessed by blinded independent central review per RECIST v1.1 criteria. Secondary end points include time to subsequent therapy, time to symptomatic progression, adverse effects, clinical laboratory abnormalities, and patient-reported outcomes.

Patients 18 years and older with at least 1 measurable lesion per RECIST v1.1 guidelines and an ECOG performance status of 0 or 1 are able to enroll on the trial. Additional eligibility criteria include having any prior toxicities resolved and treatment with osimertinib monotherapy as the most recent line of therapy. Those who received any kind of neoadjuvant or adjuvant treatment were eligible for enrollment if disease progression to locally advanced or metastatic disease occurred at 12 or more months following the last dose of such treatment and the patient had progression on or after osimertinib in the advanced or metastatic setting.

The FDA accepted a supplemental biologics license application for amivantamab plus chemotherapy as a treatment for patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations in August 2023.² Supporting data intended to confirm the clinical benefit of amivantamab in this population came from the phase 3 PAPILLON trial (NCT04538664).

References

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 Pharmaceutical Companies of Johnson & Johnson. September 6, 2023. Accessed September 6, 2023. https://shorturl.at/iozAT
2. Janssen submits supplemental biologics license application to the U.S. Food and Drug Administration seeking approval of RYBREVANT® (amivantamab-vmjw) in combination with chemotherapy for the first-line treatment of patients with locally advanced or metastatic EGFR exon 20 insertion mutation-positive non-small cell lung cancer. News release. Janssen Pharmaceuticals. August 25, 2023. Accessed September 6, 2023. https://shorturl.at/lAPU8