RARITAN, N.J. - The Janssen Pharmaceutical Companies of Johnson & Johnson announced a new analysis from the CHRYSALIS (NCT02609776) study evaluating RYBREVANT (amivantamab-vmjw) monotherapy and a combination regimen with lazertinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations who progressed after osimertinib. 1 The analysis showed higher activity and longer duration of response (DOR) in patients treated with the combination therapy, demonstrating the potential benefit of targeting the extracellular (outer) and catalytic (internal) domains of EGFR, even in patients with documented resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs). 1 The results were presented in a mini-oral presentation at the European Society for Medical Oncology (ESMO) Annual Congress 2021 virtual meeting on Sunday, September 19 (Abstract #1192MO). 'Despite advances in targeted therapies, non-small cell lung cancer with EGFR mutations remains a disease with considerable unmet need, especially when prior standard treatments have failed,' said Natasha B. Leighl, M.D., MMSc, FRCPC, FASCO, Lung Medical Oncology Lead, Princess Margaret Cancer Centre in Toronto, Canada, and presenting study investigator.(+) 'This analysis shows that targeting two domains of EGFR using amivantamab and lazertinib combination therapy demonstrated higher and more durable response than targeting only one domain. These findings provide insight into a potential new treatment approach for patients whose lung cancer has progressed on standard treatment.'
In this descriptive cross-cohort analysis, patients who had progressed on osimertinib received RYBREVANT as a monotherapy (n=121), with a majority (85 percent) preselected for C797S/other EGFR resistance mutations or mesenchymal-epithelial transition (MET) amplification.1 The RYBREVANT and lazertinib combination group included patients who had progressed on osimertinib but who were chemotherapy-naive (n=45 [38 percent with EGFR/MET-based resistance]). 1 Disease response using overall response rate (ORR), per Response Evaluation Criteria in Solid Tumors Version 1.1* (RECIST v1.1) was the primary endpoint. 1,2 Antitumor activity was observed in the group treated with RYBREVANT in combination with lazertinib, with an ORR of 36 percent (95 percent confidence interval [CI]; 22 - 51), with one patient (2 percent) with complete response and 15 patients (33 percent) with partial responses (PR).1 The median DOR was 9.6 months (95 percent CI; 5.3 - not reached). 1 In contrast, the RYBREVANT monotherapy group had an ORR of 19 percent (95 percent CI; 12 - 27) and median DOR of 5.9 months (95 percent CI; 4.2 - 12.6). 1 The clinical benefit rate (CBR), which consisted of complete response, partial response or stable disease at 11 weeks or longer, was 64 percent in the combination group (95 percent CI; 49 - 78) and 48 percent in the monotherapy group (95 percent CI; 39 - 57). 1 The combination group experienced central nervous system (CNS) progression in 7 percent of patients, with 4 percent being new CNS lesions, while the monotherapy group documented 17 percent of patients with CNS progression, with 13 percent being new CNS lesions. 1 The safety profiles for both combination and monotherapy therapy were consistent with previously reported data, and no new safety signals were identified. 1 Treatment-emergent adverse events (AEs) greater than or equal to 20 percent for RYBREVANT and lazertinib as a combination therapy include infusion-related reaction (78 percent), acneiform dermatitis (51 percent), paronychia (49 percent), nausea (44 percent), hypoalbuminemia (38 percent), peripheral edema (38 percent), pruritus (31 percent), dry skin (29 percent), rash (27 percent), constipation (27 percent), stomatitis (27 percent), fatigue (27 percent), dyspnea (24 percent), increased aspartate aminotransferase (22 percent), diarrhea (22 percent), dizziness (22 percent), hypocalcemia (20 percent), vomiting (20 percent) and headache (20 percent).1 Treatment-emergent AEs greater than or equal to 20 percent for RYBREVANT as a monotherapy include infusion-related reaction (69 percent), paronychia (37 percent), acneiform dermatitis (28 percent), hypoalbuminemia (26 percent), rash (26 percent), constipation (26 percent), nausea (24 percent), dyspnea (23 percent) and pruritus (22 percent).1 In May, the U.S. Food and Drug Administration (FDA) approved RYBREVANT, a fully human bispecific antibody, as the first targeted treatment for patients with NSCLC with EGFR exon 20 insertion mutations. 3 Additional analyses of RYBREVANT are ongoing. Lazertinib was approved earlier this year in South Korea for patients with NSCLC with EFGR mutations and T90M mutations. 'The approval of RYBREVANT as a monotherapy was a pivotal moment in the treatment of patients with difficult-to-treat non-small cell lung cancer with EGFR exon 20 insertion mutations. This new analysis builds on the established safety and efficacy profile of RYBREVANT, showing its value for a broader group of patients with EGFR mutations when combined with lazertinib,' said Sylvie Laquerre, Ph.D., Vice President, Disease Area Leader, Solid Tumor Targeted Therapies, Janssen Research & Development, LLC. 'Janssen is committed to evaluating the potential of these treatments as we work toward transforming the treatment landscape for people with lung cancer.' *RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, remain the same or increase in size.
RYBREVANT (amivantamab-vmjw) received accelerated approval by the U.S. FDA in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. 4 Shortly after FDA approval, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer included 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 mutationpositive advanced NSCLC. 5 Janssen has filed regulatory submissions for RYBREVANT with health authorities in Europe and other markets. RYBREVANT is being studied in multiple clinical trials, including the Phase 1/1b CHRYSALIS-2 (NCT04077463) study assessing the combination of RYBREVANT and lazertinib in patients who have progressed after treatment with osimertinib and chemotherapy; as first-line therapy in untreated advanced EGFR-mutated NSCLC in the Phase 3 MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib; the planned Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of lazertinib, RYBREVANT and carboplatin-pemetrexed versus carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR exon 19 deletion or exon 21 L858R substitution NSCLC after osimertinib failure; the Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin-pemetrexed versus chemotherapy alone in patients with advanced or metastatic EGFR-mutated NSCLC and exon 20 insertion mutations; and the Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of RYBREVANT based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for RYBREVANT SC delivery. 6,7,8,9,10,11 *Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer V.5.2021. National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed June 15, 2021. To view the most recent and complete version of the guidelines, visit NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
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Cautions Concerning Forward-Looking Statements
This press release contains 'forward-looking statements' as defined in the Private Securities Litigation Reform Act of 1995 regarding 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 Janssen Research & Development, LLC, Janssen Biotech, Inc., any of the other Janssen Pharmaceutical companies, and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 3, 2021, including in the sections captioned 'Cautionary Note Regarding Forward-Looking Statements' and 'Item 1A. Risk Factors,' and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forwardlooking statement as a result of new information or future events or developments.
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