FDA to Review sBLA for Amivantamab Plus Chemo in EGFRm Advanced NSCLC

• A supplemental biologics license application (sBLA) submitted to the FDA seeks approval for the use of amivantamab-vmjw (Rybrevant) plus chemotherapy in locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR mutations after disease progression on or after osimertinib (Tagrisso).
• The phase 3 MARIPOSA-2 study (NCT04988295) provides supporting data for the sBLA, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) among patients with EGFR-mutated NSCLC.
• The study met its primary end point, and the topline analysis did not reveal any new safety signals for amivantamab plus chemotherapy.

A sBLA seeking the approval of amivantamab-vmjw combined with chemotherapy consisting of carboplatin and pemetrexed has been submitted to the FDA for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions (ex19del) or L858R substitution after disease progression on or after osimertinib.¹

Data from the phase 3 MARIPOSA-2 support this sBLA as amivantamab with chemotherapy administered with or without lazertinib (Leclaza) generated a statistically significant and clinically meaningful improvement in PFS among patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC. With this finding, the study met its primary end point.

The topline analysis of the MARIPOSA-2 study also did not display any new safety signals for amivantamab when added to chemotherapy.

“We saw that in the 2 arms of chemotherapy plus amivantamab [with or without] lazertinib, we have a benefit as compared with chemotherapy…We need to wait a little bit more to also study PFS2 and [overall survival] ial from this MARIPOSA-2 study, but we can see that we have significant and clinically meaningful central nervous system [CNS] efficacy with this regimen. Protecting the patients from CNS disease is clearly an end point and clinical objective,” Nicolas Girard, MD, professor of Respiratory Medicine, Versailles Saint Quentin University, professor, head, at the Curie-Montsouris Thorax Institute, Institut Curie, told Targeted Oncology^TM.

Lungs, anterior view: © 7activestudio - stock.adobe.com

The open-label MARIPOSA-2 study included 657 patients who were randomized to receive 1 of 2 combination regimens of amivantamab with and without lazertinib and chemotherapy. Patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitutions who had disease progression on or after treatment with osimertinib were included in the trial.

The primary end point of the study was to compare the PFS as assessed by blinded independent central review (BICR) in each experimental arm compared with chemotherapy alone. Secondary end points consisted of objective response rate (ORR) as assessed by BICR, overall survival (OS), duration of response (DOR), time to subsequent therapy, PFS2, and intracranial PFS.2

Across the 3 arms, all baseline characteristics were well balanced. In the amivantamab plus chemotherapy and amivantamab plus chemotherapy and lazertinib arms, the PFS was significantly longer compared with chemotherapy alone with a hazard ratio (HR) for disease progression or death of 0.48 and 0.44, respectively (P <.001 for both).

The median PFS was 6.3 with amivantamab and chemotherapy and 8.3 with amivantamab, chemotherapy, and lazertinib vs 4.2 months for chemotherapy. PFS results were also consistent as seen by investigator assessment with the amivantamab plus chemotherapy arm at median of 8.2 months (HR, 0.41; P <.001) and 8.3 months (HR, 0.38; P <.001) for amivantamab, lazertinib, and chemotherapy, respectively, vs 4.3 months with chemotherapy.

In the amivantamab plus chemotherapy arm and the amivantamab plus lazertinib and chemotherapy arm vs chemotherapy alone, ORRs were higher at 64% and 63% vs 36%, respectively (P <.001 for both). Across arms, the median intracranial PFS rates were 12.5 months for amivantamab and chemotherapy, 12.8 months for amivantamab, lazertinib, and chemotherapy, and 8.3 months for chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively).

For safety, with the regimens containing amivantamab, predominant adverse events (AEs) were hematologic, EGFR-, and MET-related toxicities. Patients given the amivantamab plus chemotherapy combination also had lower rates of hematologic AEs compared with patients in the amivantamab, lazertinib, and chemotherapy arm.

"New treatment options are urgently needed in the post-osimertinib setting, where patients continue to face unacceptable survival rates," said Kiran Patel, MD, vice president, clinical development, solid tumors, Johnson & Johnson Innovative Medicine (also known as Janssen Research & Development) , LLC, in a press release.¹ "As we strive to transform the standard of care in patients with EGFR-mutated NSCLC, we are committed to working closely with the FDA during review of this submission for [amivantamab] in this expanded patient population."

In addition to MARIPOSA-2, amivantamab is currently under evaluation in a number of clinical trials for patients with NSCLC, including MARIPOSA (NCT04487080), PAPILLON (NCT04538664), CHRYSALIS (NCT02609776), CHRYSALIS-2 (NCT04077463), PALOMA (NCT04606381), PALOMA-2 (NCT05498428), PALOMA-3 (NCT05388669), METalmark (NCT05488314), PolyDamas (NCT05908734), and SKIPPirr study (NCT05663866).¹

REFERENCES:]

1. Janssen submits supplemental biologics license application to U.S. FDA seeking approval of rybrevant® (amivantamab-vmjw) plus chemotherapy for the treatment of patients with EGFR-mutated non-small cell lung cancer who progressed on or after osimertinib. News release. Johnson & Johnson Innovative Medicine. November 20, 2023. Accessed November 20, 2023. https://tinyurl.com/ft5x6nyx

2. Passaro A, Wang J, Wang Y, et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study [published online ahead of print, 2023 Oct 23]. Ann Oncol. 2023;S0923-7534(23)04281-3. doi:10.1016/j.annonc.2023.10.117