RARITAN - The Janssen Pharmaceutical Companies of Johnson & Johnson today announced positive topline results from the three-arm Phase 3 MARIPOSA-2 study evaluating RYBREVANT (amivantamab-vmjw), a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), given with and without lazertinib, an oral, third-generation EGFR tyrosine kinase inhibitor (TKI), combined with chemotherapy (carboplatin and pemetrexed) versus chemotherapy alone.

MARIPOSA-2 enrolled patients with locally advanced or metastatic EGFR exon 19 deletions (ex19del) or L858R substitution NSCLC after disease progression on or after osimertinib. The study met its dual primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS versus chemotherapy alone in both experimental treatment arms. No new safety signals were found for the addition of RYBREVANT to chemotherapy.[1] Janssen plans to submit these results for presentation at upcoming scientific congresses, including details on secondary endpoints such as overall survival (OS), objective response, duration of response (DoR) and intracranial PFS.

'MARIPOSA-2 provides the first Phase 3 study data of RYBREVANT-based regimens in the broader EGFR-mutated non-small cell lung cancer population,' said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. 'The study builds on the significant innovation of RYBREVANT, a first-in-class bispecific antibody targeting two major oncogenic driver pathways, with clinically meaningful results that may change the treatment paradigm.'

MARIPOSA-2 (NCT04988295) is a randomized, open-label Phase 3 study evaluating the efficacy and safety of two regimens of RYBREVANT (with and without lazertinib) and chemotherapy. Patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after osimertinib were randomized to treatment with RYBREVANT plus chemotherapy, RYBREVANT plus chemotherapy with lazertinib, or chemotherapy alone. The dual primary endpoint was used to compare the PFS (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR) for each experimental arm to chemotherapy alone. Secondary endpoints included objective response as assessed by BICR, OS, DoR, time to subsequent therapy, PFS after first subsequent therapy (PFS2) and intracranial PFS. All study participants underwent serial brain imaging to allow for the robust assessment of intracranial endpoints, and to assess the central nervous system (CNS) activity of RYBREVANT with and without lazertinib. As brain metastases can lead to significant burden and poor outcomes for patients, this aspect of the study design provides critical information in an area of high unmet need. The study enrolled 657 patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after osimertinib.1

A RYBREVANT and lazertinib combination is also being evaluated in the first-line setting for patients with EGFR-mutated NSCLC in the pivotal Phase 3 MARIPOSA study. MARIPOSA is comparing the combination therapy of RYBREVANT and lazertinib head-to-head versus osimertinib, in addition to a third arm of lazertinib to assess the contribution of components.

About RYBREVANT

RYBREVANT (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, received accelerated approval by the U.S. Food and Drug Administration (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.[2] This indication is approved under accelerated approval based on overall response rate and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. RYBREVANT has also received approval from health authorities in Europe, as well as other markets around the world.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer prefer NGS-based strategies over PCR-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.

In addition to the Phase 3 MARIPOSA-2 study, RYBREVANT is being studied in multiple clinical trials in NSCLC, including: The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT in combination with lazertinib versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.[4]

The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Topline data for this randomized Phase 3 study demonstrated statistically significant and clinically meaningful improvement in PFS in patients receiving RYBREVANT.[5]

The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT in participants with advanced NSCLC.[6]

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.[7]

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.[8]

The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.[9]

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.[10]

The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT and capmatinib combination therapy in locally advanced or metastatic NSCLC.[11]

The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT and cetrelimab combination therapy in locally advanced or metastatic NSCLC.[12]

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.[13]

About Lazertinib

Lazertinib is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. An analysis of the efficacy and safety of lazertinib from the Phase 3 study was published in The Journal of Clinical Oncology in 2023.[14] In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.[15],[16] The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.[17] Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.[18] 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.17,18,[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.[27]

Brain metastases are a common complication in a wide range of cancers, but they are particularly common among patients with EGFR-mutated lung cancer.[28] Approximately 20 percent of newly diagnosed patients with EGFR-mutated advanced NSCLC have brain metastases at diagnosis and risk of developing new metastases rise over time.28,[29],[30] Targeted systemic treatments in patients with EGFR-mutated NSCLC have CNS penetrance but, currently, clinical trials of systemic treatments largely exclude patients with brain metastases that have not been irradiated or surgically removed and the need for more therapeutic options is desired.2

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology and Pulmonary Hypertension.

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 Janssen Research and 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; competition, including technological advances, new products and patents attained by competitors; challenges to patents; 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 1, 2023, including in the sections captioned 'Cautionary Note Regarding Forward-Looking Statements' and 'Item 1A.

Contact:

Suzanne Frost

Tel: +1 416-317-0304

Email: investor-relations@its.jnj.com

(C) 2023 Electronic News Publishing, source ENP Newswire