Phase 3 Results Show First-Line Amivantamab-vmjw Plus Chemotherapy Prolongs Survival In Patients With Advanced or Metastatic NSCLC

First-line treatment with amivantamab-vmjw (Rybrevant; Janssen) and carboplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, according to the authors of a study published in The New England Journal of Medicine.

Amivantamab-vmjw plus carboplatin-based chemotherapy reduced risk of disease progression or death by 60% compared to chemotherapy alone, according to study findings.

Amivantamab-vmjw plus carboplatin-based chemotherapy reduced risk of disease progression or death by 60% compared to chemotherapy alone, according to study findings. Image Credit: © Dr_Microbe - stock.adobe.com

"PAPILLON is the first randomized phase 3 study to show clinically meaningful results for a targeted therapy in combination with chemotherapy – a regimen with the potential to become a practice-changing first-line treatment for these patients," said Kiran Patel, MD, vice president, clinical development, solid tumors, Janssen Research & Development, LLC, in the press release.

Data already suggest that amivantamab-vmjw, a bispecific antibody that binds to EGFR and MET, can improve outcomes as second-line treatment following chemotherapy, according to study author Nicolas Girard, MD, professor of respiratory medicine at Versailles Saint Quentin University and chair of the Medical Oncology Department at Institute Curie in Paris, France, in a recent press release. However, Patel explained further that this patient population needs targeted therapies for earlier use because of the tendency toward rapid progression and poor outcomes often observed with chemotherapy alone.

This randomized, open-label phase 3 PAPILLON (NCT04538664) study was conducted to evaluate the efficacy and safety of first-line amivantamab-vmjw plus chemotherapy against chemotherapy alone in patients recently diagnosed with advanced or metastatic NSCLC characterized by EGFR exon 20 insertion mutations. Investigators enrolled 308 patients who received combination treatment or chemotherapy alone. The primary endpoint was PFS, and secondary endpoints were overall response rate (ORR), PFS2 (defined as time from randomization to progression on second-line therapy), duration of response, time to subsequent therapy and overall survival (OS).

At median follow-up (14.9 months), median PFS was 11.4 months with amivantamab-vmjw/chemotherapy and 6.7 months with chemotherapy alone (HR for disease progression or death=0.395; 95 percent CI, 0.30–0.53; P<0.0001). The combination treatment was found to prolong PFS across patient subgroups. Median PFS2 was longer with combination therapy, supporting first-line use of amivantamab-vmjw plus chemotherapy.

ORR was 73% with the combination treatment and 47% with chemotherapy alone (95% CI, 65–80 and 95% CI, 39–55, respectively). At the interim analysis, 2-year OS was 72% with combination therapy and 54% with chemotherapy alone (HR=0.675; 95% CI, 0.42–1.09; P=0.106). Authors noted that most patients who received first-line chemotherapy switched to amivantamab-vmjw plus chemotherapy as second-line therapy (76%).

The most common adverse events associated with amivantamab-vmjw plus chemotherapy were grades 1 and 2 paronychia, rash, hypoalbuminemia, and peripheral edema. There were more cases of neutropenia in the amivantamab-vmjw plus chemotherapy arm as well, but treatment safety was consistent with the safety of both individual agents.

Amivantamab-vmjw is approved in the United States as a second-line treatment for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations with disease progression while on, or after, platinum-based chemotherapy. Janssen submitted a supplemental biologics license application to the FDA to approve amivantamab-vmjw/chemotherapy combination as first-line treatment for patients with NSCLC with EGFR exon 20 insertion mutations in August 2023.

"The significant improvement in PFS and in other efficacy results observed in the PAPILLON study supports amivantamab-vmjw plus chemotherapy as a potential future first-line regimen for these patients," Girard said.

Reference

New Data from Phase 3 PAPILLON Study Show RYBREVANT® (amivantamab-vmjw) Plus Chemotherapy Resulted in 60 Percent Reduction in Risk of Disease Progression or Death in Patients with Previously Untreated EGFR Exon 20 Insertion Mutation-Positive Non-Small Cell Lung Cancer. Janssen Pharmaceutical Companies of Johnson & Johnson. News Release. October 21, 2023. Accessed on January 11, 2024. https://www.prnewswire.com/news-releases/new-data-from-phase-3-papillon-study-show-rybrevant-amivantamab-vmjw-plus-chemotherapy-resulted-in-60-percent-reduction-in-risk-of-disease-progression-or-death-in-patients-with-previously-untreated-egfr-exon-20-insertion-mutati-301963753.html