RYBREVANT®▼ (amivantamab) plus chemotherapy shows positive overall survival trend versus chemotherapy in patients with previously treated EGFR-mutated lung cancer
Post-progression outcomes showed significant and sustained improvement for amivantamab plus chemotherapy, versus chemotherapy alone1
High Wycombe, UK (14 September 2024) – Johnson & Johnson today announced updated results from the Phase 3 MARIPOSA-2 study which showed RYBREVANT®▼ (amivantamab) combined with chemotherapy led to a favourable trend toward improved overall survival (OS) compared to chemotherapy alone.[1] The data also reveal consistent benefits across post-progression outcomes in adult patients with previously treated non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R Exon21 (L858R) substitution mutations.1 Results were presented at the European Society of Medical Oncology (ESMO) 2024 Congress, taking place in Barcelona, Spain from 13-17 September.1
“The positive overall survival trend seen in MARIPOSA-2 suggests that amivantamab combined with chemotherapy could potentially change the treatment landscape for a population that has historically faced limited options,” said Prof Sanjay Popat, M.D., Ph.D., Medical Oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in the United Kingdom, and presenting author.* “Building on the strong progression-free survival data previously reported from this study and by helping more patients stay on treatment for longer, we are improving their chances for better outcomes.”
At the second interim analysis for the MARIPOSA-2 clinical trial, with a median follow-up of 18.1 months, 50 percent of patients treated with amivantamab plus chemotherapy were still alive at the 18-month landmark, compared to 40 percent of those receiving chemotherapy alone (median OS, 17.7 vs 15.3 months, respectively; hazard ratio [HR], 0.73; [95 percent confidence interval [CI], 0.54–0.99]; nominal P=0.039**).1 Amivantamab plus chemotherapy showed a significant improvement in treatment discontinuation rates (22 percent), with nearly five times as many patients remaining on therapy at 18 months compared to chemotherapy (4 percent) (median time-to-treatment discontinuation [TTD], 10.4 vs 4.5 months, respectively; HR, 0.42; [95 percent CI, 0.33–0.53]; nominal P<0.0001**).1 Additionally, patients treated with amivantamab plus chemotherapy experienced a 27 percent reduction in the risk of symptomatic progression (median time to symptomatic progression [TTSP] 16.0 vs 11.8 months; HR, 0.73; [95 percent CI, 0.55–0.96]; nominal P=0.026**).1 The time to subsequent therapy was significantly prolonged with the amivantamab plus chemotherapy combination compared to chemotherapy (median time to subsequent therapy [TTST], 12.2 vs 6.6 months, respectively; HR, 0.51; [95 percent CI, 0.39–0.65]; nominal P<0.0001**), which also reduced the risk of second disease progression or death by 39 percent (median progression-free survival 2 [PFS2], 16.0 vs 11.6 months, respectively; HR, 0.64; [95 percent CI, 0.48–0.85]; nominal P=0.002**).1
“While diverse resistance mechanisms in treated EGFR-mutant non-small cell lung cancer can present a challenge in relapsed disease, the latest findings from the MARIPOSA-2 study reveal that combining amivantamab with chemotherapy markedly extends progression-free survival and holds promise for improving overall survival compared to chemotherapy alone in the relapsed setting,” said Dr John Fleming, Country Medical Director, Johnson & Johnson Innovative Medicine, UK. “These results reaffirm J&J’s focus on advancing precision medicine across all lines of NSCLC, with the goal of offering novel treatment options and more durable therapies to better support patients in need.’’
In the primary analysis of the MARIPOSA-2 study, presented at the European Society for Medical Oncology (ESMO) 2023 Congress, adverse events (AEs) of Grade 3 or higher, mainly due to haematologic toxicities, were reported by 72 percent of patients treated with amivantamab plus chemotherapy, and 48 percent with chemotherapy alone.[2] The most common Grade 3 or higher AEs included neutropenia, thrombocytopenia, anaemia, and leukopenia.2 Grade 3 or 4 bleeding events were seen in 1 percent of patients treated with amivantamab plus chemotherapy, and in no patients with chemotherapy.2 Serious treatment-emergent AEs (TEAEs) were observed in 32 percent of patients treated with amivantamab plus chemotherapy and 20 percent with chemotherapy.2 Infusion-related reactions in the amivantamab plus chemotherapy arm were 58 percent (all grades) and 5 percent (Grade >3 or above).2 Treatment-related AEs leading to death were infrequent in all arms (2 percent vs. 1 percent) in the amivantamab plus chemotherapy and chemotherapy alone arms respectively.2 Permanent discontinuation of all study agents in amivantamab plus chemotherapy arm due to adverse reactions occurred in 11 percent of patients.2
[1] Popat, et al. Overall Survival Among Patients Receiving Amivantamab Plus Chemotherapy vs Chemotherapy in EGFR-mutated, Advanced Non-small Cell Lung Cancer After Disease Progression on Osimertinib (MARIPOSA-2). 2024 European Society for Medical Oncology. September 14, 2024.
[2] Passaro P, et al. Amivantamab Plus Chemotherapy (With or Withoutlazertinib) vs Chemotherapy Alone in EGFR-mutated, Advanced Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib: MARIPOSA-2, a Phase 3, Global, Randomized, Controlled Trial. 2023 European Society for Medical Oncology. October 23, 2023.
