Phase 3 PAPILLON study showed RYBREVANT® in combination with carboplatin and pemetrexed significantly improved progression-free survival, reducing the risk of disease progression or death by 60 per cent versus carboplatin and pemetrexed alone in patients with previously untreated NSCLC with EGFR exon 20 insertion mutations.1
"Patients with EGFR Exon 20 mutated non-small cell lung cancer face an aggressive disease with a worse prognosis than those with other EGFR mutations. There is a significant unmet need to improve the effectiveness of treatment for patients with this type of lung cancer," says Dr.
"The treatment of lung cancer has been strongly influenced by an improved understanding of the underlying biology behind this disease. Understanding the mechanism of action of certain genetic alterations such as EGFR mutations has allowed exciting new anti-cancer therapies to improve survival in patients touched with these diseases. However, there are still significant treatment gaps to bridge, in particular, in relation to EGFR Exon 20 insertion mutations," says Dr.
In Canada, lung cancer is the most commonly diagnosed cancer, with an estimated 31,000 new cases in 2023.2 It is also responsible for 24 per cent of all cancer deaths among Canadians.2 An estimated 15 per cent of Canadians with non-squamous NSCLC have an activating EGFR mutation.3 The frequency of EGFR mutations is even greater in patients of Asian descent (~39 per cent) and in
"The approval of RYBREVANT® offers a promising and urgently needed new first-line treatment option and represents significant advancement for those battling this rare mutation," says
The Health Canada NOC is based on results from the Phase 3, randomized, open-label, multicenter PAPILLON study.1 The study compared treatment with RYBREVANT® in combination with platinum-based chemotherapy to treatment with platinum-based chemotherapy alone in patients with treatment-naïve, locally advanced or metastatic NSCLC with EGFR Exon 20 insertion mutations, as identified by local testing.1 A total of 308 patients were randomized (1:1) to receive RYBREVANT® in combination with platinum-based chemotherapy (N=153) or platinum-based chemotherapy alone (N=155).1 The results demonstrated RYBREVANT® in combination with platinum-based chemotherapy provides a clinically meaningful and statistically significant improvement in progression-free survival (PFS) and a 60 per cent reduction in the risk of disease progression or death compared to platinum-based chemotherapy alone.1
Among 151 patients who received RYBREVANT® in combination with platinum-based chemotherapy, the median duration of treatment was 9.7 months (range: 0.1 to 26.9 months), with 76% were exposed for 6 months or longer and 38% were exposed for greater than one year.1 Serious adverse events occurred in 37.1 per cent of patients who received RYBREVANT® in combination with platinum-based chemotherapy.1 Fatal adverse events, irrespective of relatedness to treatment, occurred in 7 patients (4.6 per cent) who received RYBREVANT® in combination with platinum-based chemotherapy.1 The most common treatment-emergent adverse events (≥ 20 per cent) were rash, neutropenia, paronychia, anaemia, stomatitis, infusion-related reactions, hypoalbuminaemia, edema, constipation, leukopenia, nausea, thrombocytopenia, decreased appetite, fatigue, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, COVID-19, hypokalaemia, vomiting, and diarrhea.1 The most common Grade 3 to 4 laboratory abnormalities (≥ 2 per cent) were decreased albumin, increased ALT, increased gamma-glutamyltransferase, decreased sodium, decreased potassium, decreased magnesium and decreases in white blood cells, hemoglobin, neutrophils, platelets, and lymphocytes.1
"This approval reinforces our commitment to developing novel therapies, particularly for underserved patient populations with significant unmet needs," says
About RYBREVANT®
RYBREVANT® 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.1 It binds extracellularly, or to the outside of the cell, slowing or inhibiting tumour growth and leading to tumour cell death.1 RYBREVANT®, indicated as a monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR Exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, has been issued a marketing authorization with conditions.1 RYBREVANT®, indicated in combination with platinum-based chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced (not amenable to curative therapy) or metastatic NSCLC with activating EGFR Exon 20 insertion mutations, has been issued a market authorization without conditions.1 A validated test is required to identify EGFR Exon 20 insertions mutation-positive status prior to treatment.1
About the PAPILLON Study
PAPILLON (NCT04538664) is a Phase 3 randomized, open-label study evaluating the efficacy and safety of RYBREVANT® in combination with platinum-based chemotherapy (carboplatin and pemetrexed), compared with platinum-based 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 overall response rate (ORR) and overall survival (OS). Patients who received platinum-based chemotherapy alone were allowed to receive RYBREVANT® monotherapy in the second-line setting after confirmation of disease progression.10
About
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and
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). 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
* Dr.
** Dr.
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1 | RYBREVANT® Product Monograph, |
2 | 2023 Faces of Lung Cancer Report. |
3 | Cheema PK, Gomes M, Banerji S, et al. Consensus recommendations for optimizing biomarker testing to identify and treat advanced EGFR-mutated non-small-cell lung cancer. Curr Oncol. 2020;27(6):321-329. doi:10.3747/co.27.7297 |
4 | Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. doi:10.18632/oncotarget.12587 |
5 | Midha A, |
6 | Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220-229. doi:10.1158/1535-7163.MCT-12-0620 |
7 | Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-184. doi:10.1097/JTO.0b013e3182779d18 |
8 | Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Signal Transduct Target Ther. 2019;4:5. Published 2019 |
9 | Bazhenova L, Minchom A, Viteri S, et al. Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. |
10 | ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). |
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