Johnson & Johnson Submits Supplemental Biologics License Application and New Drug Application to U.S. FDA Seeking Approval of RYBREVANT® (amivantamab-vmjw) Plus Lazertinib for the Treatment of Patients with EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC)

Submissions supported by data from landmark Phase 3 MARIPOSA study, which showed statistically significant and clinically meaningful improvement in progression-free survival in patients with EGFR-mutated advanced NSCLC treated with RYBREVANT^® plus lazertinib versus osimertinib

RARITAN, NJ, USA I December 21, 2023 I Johnson & Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) together with a New Drug Application (NDA) seeking the approval of RYBREVANT^® (amivantamab-vmjw) in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. 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 Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. “We believe this targeted, chemotherapy-free regimen may have the potential to transform the treatment of EGFR-mutated NSCLC, and we look forward to working with the FDA in review of these applications.” 

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 European Society of Medical Oncology (ESMO) 2023 Congress (Abstract #LBA14).

About the MARIPOSA Study

MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT^®1 (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 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 ORR 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 supplemental Biologics License Application (sBLA) Johnson & Johnson submitted to the U.S. FDA for RYBREVANT^® in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations has been granted priority review. In October 2023, a type II extension of indication application was submitted to the European Medicines Agency (EMA) seeking approval of RYBREVANT^® for this indication. In November 2023, Johnson & Johnson submitted an sBLA to the U.S. FDA for RYBREVANT^® in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib. A type II extension of indication application was also submitted to the EMA seeking the approval of RYBREVANT^® for this indication.

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 Congress demonstrated statistically significant and clinically meaningful improvement in PFS in patients receiving RYBREVANT^® plus chemotherapy with and without lazertinib versus chemotherapy.⁴
• 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 Congress demonstrated statistically significant and clinically meaningful improvement in PFS in patients receiving RYBREVANT^® versus chemotherapy.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
• 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.¹⁴

For more information, visit: https://www.RYBREVANT.com.

About Lazertinib

In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of 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 LASER301 study was published in The Journal of Clinical Oncology in 2023.¹⁵

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.^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.²⁷

Please read the full Prescribing Information for RYBREVANT^®.

About Johnson & Johnson

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 MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are both Johnson & Johnson companies.

^*RECIST (v1.1) 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, stay the same or get bigger.

^‡The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no representations or warranties and explicitly disclaims the appropriateness or applicability of the NCCN Content to any specific patient’s care or treatment.

^§See the NCCN Guidelines for detailed recommendations, including other treatment options.

^∥The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

SOURCE: Johnson & Johnson