Janssen-Cilag International NV, a Johnson & Johnson company, has announced updated results from the Phase 3 MARIPOSA-2 study, revealing a favorable trend toward improved overall survival (OS) in adult patients with previously treated non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations when treated with RYBREVANT® (amivantamab) combined with chemotherapy. The data, presented at the European Society of Medical Oncology (ESMO) 2024 Congress, also demonstrated consistent benefits across post-progression outcomes compared to chemotherapy alone.
At the second interim analysis, 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).
Improved Treatment Outcomes
Amivantamab plus chemotherapy showed a significant improvement in treatment discontinuation rates, with nearly five times as many patients remaining on therapy at 18 months (22 percent) compared to chemotherapy (4 percent) (median time-to-treatment discontinuation [TTD], 10.4 vs 4.5 months, respectively) [95 percent CI, 0.33–0.53]; nominal P <0.0001. 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). The time to subsequent therapy was significantly prolonged with the amivantamab 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 36 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).
Expert Commentary
“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, FRCP, 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.”
Safety Profile
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. The most common Grade 3 or higher AEs included neutropenia, thrombocytopenia, anaemia, and leukopenia. Grade 3 or 4 bleeding events were seen in one percent of patients treated with amivantamab plus chemotherapy, and in no patients with chemotherapy. Serious treatment-emergent AEs (TEAEs) were observed in 32 percent of patients treated with amivantamab plus chemotherapy and 20 percent with chemotherapy. Treatment-related AEs leading to death were infrequent in all arms (2 percent vs. 0.4 percent) in the amivantamab plus chemotherapy and chemotherapy alone arms respectively. Permanent discontinuation of all study agents in amivantamab plus chemotherapy arm due to adverse reactions occurred in 11 (8 percent) patients.
Regulatory Approval
Amivantamab plus chemotherapy received approval from the European Commission in August 2024 for the treatment of adults with advanced NSCLC with EGFR ex19del or L858R mutations, after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI), based upon the MARIPOSA-2 study.
About MARIPOSA-2
MARIPOSA-2 (NCT04988295), which enrolled 657 patients, is a randomised, open-label Phase 3 study evaluating the efficacy and safety of two combination regimens of amivantamab (with and without lazertinib) and chemotherapy. Patients with locally-advanced or metastatic EGFR ex19del or exon 21 L858R substitution NSCLC who had disease progression on or after treatment with osimertinib were randomised to treatment with amivantamab plus chemotherapy, amivantamab plus chemotherapy with lazertinib, or chemotherapy alone. The dual primary endpoint was used to compare the progression-free survival (PFS) (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR) for each experimental arm to chemotherapy alone. Secondary endpoints included objective response as assessed by BICR, overall survival (OS), duration of response (DOR), time to subsequent therapy, PFS2 and intracranial PFS.
About Amivantamab
Amivantamab is a fully-human EGFR-MET bispecific antibody that acts by targeting tumours with activating and resistance EGFR mutations and MET mutations and amplifications, and by harnessing the immune system.
