FDA Approves Amivantamab Plus Chemo for EGFR+ Advanced NSCLC After an EGFR Inhibitor

FDA

The FDA has approved amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed for adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR TKI.¹

The regulatory decision was supported by data from the phase 3 MARIPOSA-2 trial (NCT04988295), which showed that the median progression-free survival (PFS) was 6.3 months (95% CI, 5.6-8.4) in the amivantamab arm compared with 4.2 months (95% CI, 4.0-4.4) in the chemotherapy arm (HR, 0.48; 95% CI, 0.36-0.64; P < .0001). Amivantamab plus chemotherapy elicited a confirmed overall response rate of 53% (95% CI, 44%-62%) vs 29% (95% CI, 23%-35%) for chemotherapy alone (P < .0001).

Data from a prespecified second interim analysis showed there was no statistically significant difference in overall survival (stratified HR, 0.73; 95% CI, 0.54-0.99).

"[Amivantamab] plus chemotherapy may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib [Tagrisso], in the first line," Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard, stated in a news release.² "This multitargeted combination extended PFS and improved ORR compared [with] chemotherapy alone, offering an important and effective new second-line option for patients."

MARIPOSA-2 was a randomized, open-label, phase 3 study that evaluated the efficacy and safety of amivantamab plus chemotherapy with or without lazertinib (Lazcluze). Investigators enrolled patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations who experienced disease progression on or after treatment with osimertinib.

Patients were randomly assigned 1:2:2 to treatment with amivantamab plus carboplatin and pemetrexed; amivantamab plus carboplatin, pemetrexed, and lazertinib; or carboplatin and pemetrexed alone.¹

Blinded independent central review (BICR)–assessed PFS per RECIST 1.1 criteria for the 2 experimental arms vs the chemotherapy arm served as the trial's primary end points. Secondary end points included BICR-assessed ORR, OS, duration of response, time to subsequent therapy, time to second progression, and intracranial PFS.

The most common adverse effects reported in at least 20% of patients with the amivantamab regimen were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.

"This milestone reinforces [amivantamab] as an important treatment option for patients with EGFR-mutated NSCLC who continue to face high unmet needs after disease progression on or after TKI therapy," Kiran Patel, MD, vice president, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine, added in a news release.² "Patients need and deserve effective, targeted approaches across all lines of therapy. With [amivantamab]-based regimens, we are bringing potential new standards of care to the nearly 30,000 patients diagnosed with EGFR-mutated NSCLC in the United States each year."

References

1. FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations. FDA. September 19, 2024. Accessed September 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-carboplatin-and-pemetrexed-non-small-cell-lung-cancer-egfr-exon-19
2. Rybrevant (amivantamab-vmjw) plus standard of care approved in the U.S. as first and only targeted regimen to cut risk of disease progression by more than half in second-line EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. September 19, 2024. Accessed September 19, 2024. https://www.investor.jnj.com/news/news-details/2024/RYBREVANT-amivantamab-vmjw-plus-standard-of-care-approved-in-the-U.S.-as-first-and-only-targeted-regimen-to-cut-risk-of-disease-progression-by-more-than-half-in-second-line-EGFR-mutated-advanced-lung-cancer/default.aspx