The European Medicines Company’s Committee for Medicinal Merchandise for Human Use (CHMP) has advisable the approval of amivantamab-vmjw (Rybrevant) together with carboplatin and pemetrexed for the therapy of grownup sufferers with superior non–small cell lung most cancers (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations after failure of prior remedy, together with an EGFR TKI.
The advice is supported by information from the section 3 MARIPOSA-2 trial (NCT04988295), which confirmed that amivantamab plus chemotherapy lowered the danger of illness development or demise by 52% in contrast with chemotherapy alone (HR, 0.48; 95% CI, 0.36-0.64; P < .001). Sufferers within the amivantamab arm skilled a median progression-free survival (PFS) of 6.3 months vs 4.2 months for chemotherapy alone. Moreover, amivantamab plus chemotherapy elicited an goal response fee (ORR) of 64% vs 36% for chemotherapy alone.
“Resistance mechanisms after illness development on osimertinib are numerous and polyclonal, with as much as half being EGFR and MET-based alterations. There are not any focused therapies permitted for the post-osimertinib (Tagrisso) setting, and outcomes with the present commonplace of care, platinum-based chemotherapy, are poor,” Antonio Passaro, MD, PhD, medical oncologist within the Division of Thoracic Oncology on the European Institute of Oncology in Milan, Italy, said in a information launch. “The mix of amivantamab and chemotherapy presents renewed hope and a brand new commonplace of take care of these sufferers, with enhancements noticed in ORR, PFS, and intracranial efficacy, even in sufferers with beforehand untreated mind metastases.”
The open-label MARIPOSA-2 trial enrolled 657 sufferers with locally-advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations who skilled illness development on or after therapy with osimertinib.
Sufferers had been randomly assigned to acquired amivantamab plus chemotherapy; amivantamab plus chemotherapy and lazertinib (Leclaza); or chemotherapy alone.
PFS per RECIST 1.1 standards by blinded impartial central overview (BICR) evaluation for every amivantamab-containing arm vs chemotherapy alone served because the trial’s main finish level. Secondary finish factors included BICR-assessed ORR, total survival (OS), period of response (DOR), time to subsequent remedy, time to second development and intracranial PFS.
Further information confirmed 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).
Concerning security, grade 3 or increased antagonistic results (AEs) occurred in 72% of sufferers within the amivantamab plus chemotherapy arm vs 48% of sufferers within the chemotherapy alone arm. The commonest grade 3 or increased AEs included neutropenia, thrombocytopenia, anemia, and leukopenia.
Grade 3 or 4 bleeding occasions had been reported in 1% of sufferers given amivantamab plus chemotherapy, and no such occasions occurred within the chemotherapy arm.
The charges of significant treatment-emergent AEs (TEAEs) had been 32% for amivantamab plus chemotherapy vs 20% for chemotherapy alone. Fifty-eight % of sufferers within the amivantamab arm skilled infusion-related reactions. Therapy-related AEs led to demise occurred in 2% of sufferers within the experimental arm vs 1% of sufferers within the chemotherapy arm.
“At present’s constructive CHMP opinion is welcome information and demonstrates the outcomes of our deep dedication to remodeling outcomes for sufferers with NSCLC,” Kiran Patel, MD, vp of Medical Growth, Strong Tumors, at Johnson & Johnson Progressive Medication, said within the information launch. “Amivantamab has already proven constructive outcomes in treating sufferers with different EGFR mutations, and we now sit up for the subsequent steps in making it out there to additional sufferers with widespread EGFR mutations after development on osimertinib.”
Reference
CHMP recommends Rybrevant (amivantamab) together with chemotherapy for the therapy of grownup sufferers with superior EGFR-mutated non-small cell lung most cancers (NSCLC) after failure of prior remedy. Information launch. Janssen-Cilag Worldwide. 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
