CHMP Promotes Positive Opinion of Amivantamab in EGFR Exon 20+ NSCLC

In March 2024, the FDA approved amivantamab plus chemotherapy for patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations as detected with an FDA-approved test.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended amivantamab (Rybrevant) plus carboplatin and pemetrexed for approval in the first-line setting for patients with advanced non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, according to a press release from the developers, Janssen-Cilag International NV.¹

This recommendation is based on results from the phase 3 PAPILLON study (NCT04538664) that assessed intravenous amivantamab plus chemotherapy or chemotherapy alone.² The primary end point of progression-free survival (PFS) by blinded independent central review (BICR) was met in the combination arm (HR, 0.395; 95% CI, 0.30-0.53; P <.0001). Overall survival (OS) data also showed promising results for the combination arm (HR, 0.675; 95% CI, 0.42-1.09; P = .106).

The safety profile of amivantamab plus chemotherapy remained consistent with previously reported results. A total of 7% of patients discontinued therapy due to treatment-related toxicity. Adverse effects (AEs) that led to death were comparable in both arms. Grade 3 or higher AEs occurred in 75% of patients in the amivantamab arm vs 54% in the chemotherapy arm. Serious AEs occurred in 37% vs 31% of patients, respectively.

Hematologic and gastrointestinal toxicities related to chemotherapy remained comparable except for neutropenia, which was transient. Additionally, pneumonitis was reported in 3% of patients in the amivantamab arm.

“The PAPILLON study results represent an important advancement in the EGFR exon 20 insertion NSCLC treatment landscape, demonstrating significantly improved [PFS] with first-line amivantamab plus chemotherapy, vs chemotherapy alone,” trial investigator Nicolas Girard, MD, PhD, head of Medical Oncology at Institut Curie, and professor of Thoracic Oncology and Respiratory Medicine at the Paris Saclay University, France, said in the press release. “Notably, we observed improvements in functional status and reduction in lung cancer-related symptoms, underscoring the potential of this regimen to redefine standards of care for these patients, offering hope for improved quality of life and patient-relevant treatment outcomes.”

The PAPILLON trial enrolled 308 patients and was designed to evaluate the safety and efficacy of the combination compared with chemotherapy alone. The primary end point was PFS by BICR. Secondary end points included overall response rate, PFS after the first subsequent therapy, duration of response, time to subsequent therapy, and OS.

Patients who had disease progression following chemotherapy alone in the PAPILLON trial were eligible to receive amivantamab monotherapy as second-line treatment.

“Today’s positive opinion represents the culmination of years of work and our team’s commitment to the lung cancer community. We will continue to focus on redefining treatment paradigms, starting from the very first line of therapy, with a goal of improving survival rates and overall patient outcomes.” Kiran Patel, MD, vice president of Clinical Development, Solid Tumors, at Johnson & Johnson Research & Development, said. “Through our extensive research and development efforts, we are pioneering novel approaches and targeting key pathways implicated in lung cancer progression, with the ultimate goal of transforming clinical outcomes for patients with EGFR-mutated NSCLC.”

In March 2024, the FDA approved amivantamab plus chemotherapy for patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations as detected with an FDA-approved test.³ Regular approval was also granted to those with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

The FDA approved the amivantamab combination based on results from the PAPILLON trial.

References

1. Johnson & Johnson receives positive CHMP opinion for RYBREVANT®(amivantamab) in combination with chemotherapy for the first-line treatment of patients with advanced non-small cell lung cancer with activating EGFR exon 20 insertion mutations. News release. Johnson & Johnson. April 26, 2024. Accessed April 29, 2024. https://shorturl.at/isxJX
2. Zhou C, Tang K, Cho BC, et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051. doi:10.1056/NEJMoa2306441
3. FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. News release. FDA. March 1, 2024. Accessed April 29, 2024. https://tinyurl.com/msw4u5yk