Janssen Submits Supplemental Biologics License Application to the U.S. Food and Drug Administration Seeking Approval of RYBREVANT® (amivantamab-vmjw) in Combination with Chemotherapy for the First-line Treatment of Patients with Locally Advanced or Metast

2023-08-25

临床结果临床3期临床2期加速审批上市批准

Application is supported by data from PAPILLON, the first randomized Phase 3 study to show clinically meaningful results in patients with NSCLC with EGFR exon 20 insertion mutations

RARITAN, NJ, USA I August 25, 2023 I The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking the expanded approval of RYBREVANT® (amivantamab-vmjw) in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. The sBLA is being reviewed by the FDA through the Real-Time Oncology Review (RTOR) program.*

"PAPILLON is the first randomized Phase 3 study in patients with NSCLC with EGFR exon 20 insertion mutations to show clinically meaningful results. This creates an opportunity to make a significant improvement to the standard of care for this patient population with high unmet medical need," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "We look forward to working with the FDA through the RTOR pathway in pursuit of an approval for RYBREVANT plus chemotherapy as we simultaneously progress the development of this novel bispecific antibody in additional patient populations."

Following Breakthrough Therapy Designation from the U.S. FDA in 2020, RYBREVANT® received accelerated approval in 2021 as the first fully-human, bispecific antibody for the treatment of patients with NSCLC with EGFR exon 20 insertion mutations.2 The sBLA submission for RYBREVANT® is also intended to satisfy the regulatory requirements of the accelerated approval confirming the clinical benefit observed in the Phase 1 CHRYSALIS study.

The sBLA is supported by data from the Phase 3 PAPILLON (NCT04538664) clinical trial, a randomized, open-label study evaluating the efficacy and safety of RYBREVANT® in combination with chemotherapy as first-line treatment in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.1,2 In July, Janssen announced the PAPILLON study met its primary endpoint with a statistically significant and clinically meaningful improvement in PFS (as measured by BICR) in patients receiving RYBREVANT® plus chemotherapy versus chemotherapy alone.1 The combination of RYBREVANT® and chemotherapy demonstrated a safety profile consistent with the safety profiles of the individual components.1

About PAPILLON

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.1 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), PFS after first subsequent therapy, time to symptomatic progression and overall survival (OS).1 Patients who received chemotherapy alone were allowed to receive RYBREVANT® monotherapy in the second-line setting after confirmation of disease progression.1

About RYBREVANT®

RYBREVANT® (amivantamab-vmjw) 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 duration of response. 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.9†^

In addition to the Phase 3 PAPILLON study, RYBREVANT® is being studied in multiple clinical trials in NSCLC, including:

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

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.20,21 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.22 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.23 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.22-28 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 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.32 Patients with EGFR exon 20 insertion mutations have a real-world five-year OS of 8 percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.33

Please read the full Prescribing Information for RYBREVANT®.

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.

Learn more at www.janssen.com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Biotech, Inc. and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

*The Real-Time Oncology Review (RTOR) program aims to provide a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant.34

**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, 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.

1 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed 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). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed July 2023.

2 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

3 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Molecular Cancer Therapeutics. 2013; Feb; 12(2):220-9.

4 Vyse, S., Huang, P.H. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Sig Transduct Target Ther 4, 5 (2019).

5 Oxnard, JR et. al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18.

6 Remon, J et al. EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins. Cancer Treatment Reviews. 90 (2020).

7 Baraibar I et al. Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Critical Reviews in Oncology. 2020.

8 O'Leary C, Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small-Cell Lung Cancer (NSCLC). Pharmaceuticals. 2020, 13, 273; doi:10.3390/ph13100273/.

9 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2022.© National Comprehensive Cancer Network, Inc.Cancer Network, Inc. 2022. All rights reserved. Accessed March 22, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.

10 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). Available at: https://clinicaltrials.gov/ct2/show/NCT04487080. Accessed July 2023.

11 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). Available at: https://clinicaltrials.gov/ct2/show/NCT04988295. Accessed July 2023.

12 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). Available at: https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed July 2023.

13 ClinicalTrials.gov. A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). Available at: https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed July 2023.

14 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/ct2/show/NCT04606381. Accessed May 2023.

15 ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). Available at: https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed July 2023.

16 ClinicalTrials.gov. A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). Available at: https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed July 2023.

17 ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). Available at: https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed July 2023.

18 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). Available at: https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1. Accessed July 2023.

19 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed July 2023.

20 The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed July 2023.

21 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed July 2023.

22 Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18.

23 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.

24 Riess JW, et al. Diverse EGFR exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. J Thorac Oncol. 2018;13(10):1560-1568. doi:10.1016/j.jtho.2018.06.019.

25 Pennell NA, et al. A phase II trial pf adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 37:97-104.

26 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.

27 Zhang YL, 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.

28 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911.

29 American Lung Association. EGFR and Lung Cancer. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed July 2023.

30 Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site.

31 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65.

32 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Molecular Cancer Therapeutics. 2013; Feb; 12(2):220-9.

33 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.

34 FDA.gov. Real-Time Oncology Review. Available at: https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review. Accessed August 2023.

SOURCE: Janssen