Based on the Phase 3 MARIPOSA study, this marks the third submission from the RYBREVANT clinical development program in four months, following sBLA submissions for MARIPOSA-2 and PAPILLON.
'The combination of RYBREVANT and lazertinib demonstrated statistically significant and clinically meaningful improvement in progression-free survival compared to osimertinib in patients with previously untreated EGFR-mutated NSCLC. This remains an area of high unmet need as patients often experience treatment resistance and disease progression on currently available therapies,' said
These applications are supported by data from the Phase 3 MARIPOSA (NCT04487080) study evaluating the efficacy and safety of RYBREVANT in combination with lazertinib versus osimertinib and versus lazertinib alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.1,2 Results from the MARIPOSA study were recently presented in a Presidential Symposium at the
About the MARIPOSA Study
MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT1 (amivantamab-vmjw), a bispecific antibody targeting EGFR and mesenchymal-epithelial transition (MET), in combination with lazertinib, an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), versus osimertinib and versus lazertinib alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations. The primary endpoint of the study is progression-free survival (PFS) (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR). Secondary endpoints include OS, ORR, DOR, second progression-free survival (PFS2) and intracranial PFS.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. The primary endpoint of PFS in MARIPOSA included these central nervous system (CNS) events detected by serial brain MRIs. Extracranial PFS, which may more closely approximate what would be seen in other trials, was also explored in MARIPOSA.
About RYBREVANT
RYBREVANT (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, received accelerated approval by the
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC(++) prefer next-generation sequencing-based strategies over polymerase chain reaction-based approaches for the detection of EGFR exon 20 insertion variants and include amivantamab-vmjw (RYBREVANT) as a subsequent therapy option with a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.3
In addition to the Phase 3 MARIPOSA study, RYBREVANT is being studied in multiple clinical trials in NSCLC, including: The Phase 3 MARIPOSA-2 (NCT04988295) study evaluating the efficacy and safety of RYBREVANT and chemotherapy in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after treatment with osimertinib. Data for this randomized Phase 3 study presented at the ESMO 2023
The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin-pemetrexed versus carboplatin-pemetrexed in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Data for this randomized Phase 3 study presented at the ESMO 2023
The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT in participants with advanced NSCLC.
The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.
The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab SC delivery.
The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.
The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in participants with EGFR-mutated advanced or metastatic NSCLC.
The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANTand capmatinib combination therapy in locally advanced or metastatic NSCLC.
The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT and cetrelimab combination therapy in locally advanced or metastatic NSCLC.
The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.
The Phase 2 COCOON study (NCT06120140) will evaluate enhanced dermatological care to reduce rash and paronychia in patients with EGFR-mutated NSCLC treated first-line with amivantamab plus lazertinib.
About Lazertinib
In 2018,
About Non-Small Cell
Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.16,17 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.18 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.19 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.18,19,20,21,22,23 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.24 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.25,26 Patients with EGFR ex19del or L858R mutations have a real-world five-year OS of 19 percent.
About
At
Cautions Concerning Forward-Looking Statements
This press release contains 'forward-looking statements' as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of RYBREVANT (amivantamab-vmjw) and lazertinib. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of
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