Landmark Phase 3 MARIPOSA Study Shows RYBREVANT®▼(amivantamab) Plus Lazertinib Resulted in 30 Percent Reduction in Risk of Disease Progression or Death Compared to Osimertinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer

Landmark Phase 3 MARIPOSA Study Shows RYBREVANT®▼(amivantamab) Plus Lazertinib Resulted in 30 Percent Reduction in Risk of Disease Progression or Death Compared to Osimertinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer

Early data show an overall survival trend favoring the combination of amivantamab and lazertinib compared to osimertinib; consistent results seen in patients with and without brain metastases1

 Late-breaking results from the MARIPOSA study featured in a Presidential Symposium at 2023 ESMO Congress1

BEERSE, BELGIUM, 23 October, 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 3 MARIPOSA study showing RYBREVANT®▼ (amivantamab) in combination with lazertinib compared to osimertinib resulted in a 30 percent reduction in the risk of disease progression or death (Hazard Ratio [HR]=0.70; 95 percent Confidence Interval [CI], 0.58–0.85; P<0.001) in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with either epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution. 1 Results also showed a favourable trend in overall survival (OS) for amivantamab and lazertinib in these patients compared to osimertinib (HR=0.80; 95 percent CI, 0.61–1.05; P=0.11) at a first interim analysis. 1 These data were presented in a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2023 Congress taking place 20-24 October in Madrid, Spain (Abstract #LBA14). 1

“Despite advances in EGFR-mutated NSCLC treatment, novel targeted therapies and regimens are needed to address resistance and disease progression, which are nearly inevitable with current treatments,” said Byoung Chul Cho*, M.D., Ph.D., medical oncologist and professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Republic of Korea, and presenting author. “With the combination of amivantamab and lazertinib in the MARIPOSA study, progression free survival was significantly improved in patients with previously untreated EGFR-mutated NSCLC compared to osimertinib. These results support the potential of this amivantamab combination to be a future standard of care.”

 At a median follow-up of 22 months, median progression-free survival (PFS) for amivantamab and lazertinib was 23.7 months compared to 16.6 months for osimertinib (HR=0.70; 95 percent CI, 0.58–0.85; P<0.001). 1 Other secondary endpoints showed consistent and clinically meaningful benefits for the combination of amivantamab and lazertinib versus osimertinib across prespecified patient subgroups, including race, type of EGFR mutation, history of brain metastasis, and performance status.1† Lazertinib was included in the MARIPOSA study to determine its contribution to the combination with amivantamab, and lazertinib monotherapy was shown to provide a clinically meaningful median PFS of 18.5 months (95 percent CI, 14.8–20.1). 1

The MARIPOSA study required all patients to have serial brain imaging with MRIs in order to detect or monitor brain metastases, a measure not implemented in most prior studies for EGFR-mutated NSCLC.1 The primary endpoint of PFS in MARIPOSA included these central nervous system (CNS) events detected by serial brain MRIs.1 Extracranial PFS, which may more closely approximate what would be seen in other trials, was also explored in MARIPOSA.1 The median PFS when censoring CNS-only first progressions was 27.5 months for the combination of amivantamab and lazertinib, compared with 18.5 months for osimertinib (HR=0.68; 95% CI, 0.56–0.83; P<0.001). 1 The median duration of response (DOR), or the length of time that a tumour continues to respond to treatment without the cancer growing or spreading, was significantly longer for patients receiving amivantamab plus lazertinib compared to osimertinib, with a nine-month improvement in median DOR (25.8 vs. 16.8 months). 1

 “Lung cancer remains the leading cause of cancer death worldwide and for patients with certain oncogenic driver mutations, the survival rate with the current standard of care, tyrosine kinase inhibitors, is still too low,” said Martin Vogel, EMEA Therapeutic Area Lead Oncology, Janssen-Cilag GmbH. “There are many known actionable mutations within NSCLC, and alterations in EGFR are amongst the most common and challenging to treat. Identifying patients whose advanced NSCLC is driven by genetic mutations and providing targeted-first line treatments, such as the combination of amivantamab and lazertinib, may help address this area of particularly high unmet medical need.”

The safety profile of the combination of amivantamab and lazertinib was consistent with the safety profiles of the individual treatments, with mostly Grade 1 or 2 adverse events (AEs). 1Toxicity was largely manageable with dose interruptions and reductions, along with supportive care measures commonly used in the treatment of patients with NSCLC. The most common Grade 3 or higher treatment-related AEs were rash and paronychia.1 Amivantamab plus lazertinib had higher rates of EGFR- and MET-related AEs (hypoalbuminemia and peripheral oedema) and venous thromboembolism compared to osimertinib, with higher rates of diarrhoea being observed with osimertinib. 1 The rate of discontinuation of all study treatments due to treatment-related AEs for the amivantamab combination was 10 percent. The rate of interstitial lung disease (including pneumonitis) was less than three percent in both arms.1

 “Amivantamab is the first fully-human bispecific antibody that targets two major oncogenic driver pathways and, when combined with lazertinib, we believe, may lead to a more complete response against the tumour,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “The prolonged duration of progression-free survival and favourable trend in overall survival observed in the MARIPOSA study show the potential of amivantamab in combination with lazertinib to transform first-line treatment in EGFR-mutated NSCLC.”

Amivantamab is a bispecific antibody targeting EGFR and MET with immune cell-directing activity, and in the MARIPOSA study, was combined with lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI), to treat patients with locally advanced or metastatic EGFR-mutated NSCLC. 1,2,3,4,5,6,7 In the study, 1,074 patients were randomised to receive treatment with amivantamab plus lazertinib, osimertinib alone or lazertinib alone.1 The primary endpoint was PFS following treatment with amivantamab plus lazertinib compared to osimertinib as assessed by blinded independent central review (BICR) according to RECIST v1.1. 1‡ Secondary endpoints included OS, objective response rate (ORR), DOR and intracranial PFS.1

Results from MARIPOSA will support future planned health authority submissions.