This FDA action converts the
'When aiming for the best possible treatment outcomes, a targeted approach should be used in the first line for patients with EGFR exon 20 insertion mutations, as this is a commonly applied practice for patients with NSCLC harboring other molecular driver alterations,' said
Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.2,3 Alterations in EGFR are the most common actionable driver mutations in NSCLC.4 Clinical data show patients with EGFR exon 20 insertion mutations generally experience limited benefits with currently approved third-generation EGFR tyrosine kinase inhibitors and chemotherapy.5,6 NSCLC driven by EGFR exon 20 insertion mutations carries a worse prognosis and shorter survival rates compared with lung cancer driven by other EGFR driver mutations.7
'For patients with lung cancer and their families, each breakthrough in treatment provides not only a new option, but a potential lifeline. The approval of RYBREVANT plus chemotherapy heralds a promising new first-line treatment option for patients newly diagnosed with non-small cell lung cancer where their driver mutation is an EGFR exon 20 insertion,' said
The FDA approval is based on positive results from the randomized, open-label Phase 3 PAPILLON study, which showed RYBREVANT plus chemotherapy resulted in a 61 percent reduction in the risk of disease progression or death compared to chemotherapy alone.1 Results also showed treatment with RYBREVANT plus chemotherapy improved objective response rate (ORR) and progression-free survival (PFS).1 Based on PAPILLON data, the National Comprehensive Cancer Network (NCCN ) updated its' NCCN Clinical Practice Guidelines (NCCN Guidelines) to include a category 1 recommendation for amivantamab-vmjw (RYBREVANT) plus chemotherapy as a preferred first-line therapy for patients with NSCLC with EGFR exon 20 insertion mutations.8 (+)(++)
'We are redefining care for patients with non-small cell lung cancer by advancing innovative regimens that can be used early, with the goal of extending survival,' said
Warnings and Precautions include Infusion Related Reactions (IRR), Interstitial Lung Disease (ILD)/Pneumonitis, Dermatologic Adverse Reactions, Ocular Toxicity and Embryo-fetal Toxicity. The most common adverse reactions (20 percent) were rash, nail toxicity, stomatitis, IRR, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea and vomiting. The most common Grade 3 or 4 laboratory abnormalities (2 percent) were decreased albumin, increased alanine aminotransferase, increased gamma-glutamyl transferase, decreased sodium, decreased potassium, decreased magnesium, and decreases in white blood cells, hemoglobin, neutrophils, platelets, and lymphocytes.1
About the PAPILLON Study
PAPILLON (NCT04538664) is a randomized, open-label Phase 3 study evaluating the efficacy and safety of RYBREVANT in combination with chemotherapy, compared with chemotherapy alone, in newly diagnosed patients with advanced or metastatic NSCLC characterized by EGFR exon 20 insertion mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR). Secondary endpoints include ORR, PFS after first subsequent therapy, time to symptomatic progression and overall survival (OS). Patients who received chemotherapy alone were allowed to receive RYBREVANT monotherapy in the second-line setting after confirmation of disease progression.10
About RYBREVANT
RYBREVANT (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity is approved in 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. The NCCN Guidelines include: Amivantamab-vmjw (RYBREVANT) plus carboplatin and pemetrexed as a preferred (Category 1 recommendation) first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a subsequent therapy option (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.8 (+)(++)
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a preferred (Category 1 recommendation) subsequent therapy for patients with locally advanced or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.8 (+)(++)
Amivantamab-vmjw (RYBREVANT) as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.8 (+)(++)
In addition to the Phase 3 PAPILLON 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 MARIPOSA (NCT04487080) study assessing RYBREVANT in combination with lazertinib, a novel third-generation EGFR TKI, versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions (ex19del) or L858R substitution 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 RYBREVANT and 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.23
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.2,3 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.24 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.4 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.4,24,25,26,27,28 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.29 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.30,31 Patients with EGFR ex19del or L858R mutations have a real-world five-year OS of 19 percent.32
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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