CHMP Recommends Amivantamab Plus Chemo for Pretreated EGFR+ Advanced NSCLC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed for the treatment of adult patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations after failure of prior therapy, including an EGFR TKI.

The recommendation is supported by data from the phase 3 MARIPOSA-2 trial (NCT04988295), which showed that amivantamab plus chemotherapy reduced the risk of disease progression or death by 52% compared with chemotherapy alone (HR, 0.48; 95% CI, 0.36-0.64; P < .001). Patients in the amivantamab arm experienced a median progression-free survival (PFS) of 6.3 months vs 4.2 months for chemotherapy alone. Furthermore, amivantamab plus chemotherapy elicited an objective response rate (ORR) of 64% vs 36% for chemotherapy alone.

“Resistance mechanisms after disease progression on osimertinib are diverse and polyclonal, with up to half being EGFR and MET-based alterations. There are no targeted therapies approved for the post-osimertinib (Tagrisso) setting, and outcomes with the current standard of care, platinum-based chemotherapy, are poor,” Antonio Passaro, MD, PhD, medical oncologist in the Division of Thoracic Oncology at the European Institute of Oncology in Milan, Italy, stated in a news release. “The combination of amivantamab and chemotherapy offers renewed hope and a new standard of care for these patients, with improvements observed in ORR, PFS, and intracranial efficacy, even in patients with previously untreated brain metastases.”

The open-label MARIPOSA-2 trial enrolled 657 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 to received amivantamab plus chemotherapy; amivantamab plus chemotherapy and lazertinib (Leclaza); or chemotherapy alone.

PFS per RECIST 1.1 criteria by blinded independent central review (BICR) assessment for each amivantamab-containing arm vs chemotherapy alone served as the trial’s primary end point. Secondary end points included BICR-assessed ORR, overall survival (OS), duration of response (DOR), time to subsequent therapy, time to second progression and intracranial PFS.

Additional data showed that amivantamab plus chemotherapy generated a median intracranial PFS of 12.5 vs 8.3 months for chemotherapy alone (HR, 0.55; 95% CI, 0.38-0.79; P = .001).

Regarding safety, grade 3 or higher adverse effects (AEs) occurred in 72% of patients in the amivantamab plus chemotherapy arm vs 48% of patients in the chemotherapy alone arm. The most common grade 3 or higher AEs included neutropenia, thrombocytopenia, anemia, and leukopenia.

Grade 3 or 4 bleeding events were reported in 1% of patients given amivantamab plus chemotherapy, and no such events occurred in the chemotherapy arm.

The rates of serious treatment-emergent AEs (TEAEs) were 32% for amivantamab plus chemotherapy vs 20% for chemotherapy alone. Fifty-eight percent of patients in the amivantamab arm experienced infusion-related reactions. Treatment-related AEs led to death occurred in 2% of patients in the experimental arm vs 1% of patients in the chemotherapy arm.

“Today’s positive CHMP opinion is welcome news and demonstrates the results of our deep commitment to transforming outcomes for patients with NSCLC,” Kiran Patel, MD, vice president of Clinical Development, Solid Tumors, at Johnson & Johnson Innovative Medicine, stated in the news release. “Amivantamab has already shown positive outcomes in treating patients with other EGFR mutations, and we now look forward to the next steps in making it available to further patients with common EGFR mutations after progression on osimertinib.”

Reference

CHMP recommends Rybrevant (amivantamab) in combination with chemotherapy for the treatment of adult patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) after failure of prior therapy. News release. Janssen-Cilag International. July 26, 2024. Accessed July 26, 2024. https://www.globenewswire.com/news-release/2024/07/26/2919538/0/en/CHMP-recommends-RYBREVANT-amivantamab-in-combination-with-chemotherapy-for-the-treatment-of-adult-patients-with-advanced-EGFR-mutated-non-small-cell-lung-cancer-NSCLC-after-failure.html