Oral presentation at the International Association for the Study of Lung Cancer’s (IASLC) 2021 World Conference on Lung Cancer (WCLC) shows evidence that the bispecific mechanism of action for RYBREVANT™ can provide anti-tumor activity against either EGFR-mutated or MET-mutated non-small cell lung cancer

RARITAN, NJ, USA I August 19, 2021 I The Janssen Pharmaceutical Companies of Johnson & Johnson today announced preliminary data from the Phase 1 CHRYSALIS study evaluating RYBREVANTTM (amivantamab-vmjw) for the treatment of patients with non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) exon 14 skipping (METex14) mutations. The initial data showed anti-tumor activity in patients with METex14 mutations and a safety profile consistent with reported experience at the approved CHRYSALIS Phase 2 dose (RYBREVANTTM 1050 mg [<80 kg] / 1400 mg [≥80 kg]).1 These findings will be featured at the virtual International Association for the Study of Lung Cancer’s (IASLC) 2021 World Conference on Lung Cancer (WCLC) taking place from September 8-14 in Denver as an oral presentation (Abstract #OA15.03).

METex14 mutations are found in approximately three percent of patients with NSCLC.2 These genetic alterations result in hyperactivation of the MET receptor with corresponding cancer cell growth.3 While MET inhibitors have recently received accelerated approval in this setting in some regions, the vast majority of patients eventually acquire resistance to these therapies, thus underscoring the need for new treatment options.4,5,6  

“Newer treatment advances for non-small cell lung cancer provide benefit to patients with MET exon 14 skipping mutations, but because they are effective for only a finite period of time, patients ultimately find themselves in need of new therapies,” said Alexander Spira, M.D., Ph.D., FACP, Director of the Virginia Cancer Specialists Research Institute, Co-Chair U.S. Oncology Thoracic Program and presenting study investigator. “We look forward to sharing these latest results for amivantamab that suggest its novel mechanism of action may be of benefit to people living with this type of lung cancer.”

In the METex14 cohort of the Phase 1 CHRYSALIS study, 19 patients with this genetic alteration received intravenous RYBREVANTTM 1050 mg (for patients who weigh <80 kg) or 1400 mg (for patients who weigh ≥80 kg).1 Disease response was evaluated using overall response rate (ORR), per Response Evaluation Criteria in Solid Tumors Version 1.1* (RECIST v1.1) as the primary endpoint.1 Of the 14 response-evaluable patients, partial responses were observed in 64 percent with four patients pending confirmation.1 Activity was observed in treatment-naïve and previously-treated patients, including four of seven patients previously treated with MET tyrosine kinase inhibitors (TKIs).1 The median time to first response was 4.1 months (range, 1.6–9.9).1 

The majority of treatment-related adverse events (AEs) were Grade 1-2.1 Treatment-related Grade ≥3 AEs were observed in three patients (16 percent), which included dyspnea (N=1), hypoalbuminemia (N=1) and rash (N=1).1 The incidence of treatment-related AEs leading to dose reduction and discontinuation was 11 percent and five percent, respectively.1 Dose interruptions occurred in 32 percent of patients.1 

In May 2021, RYBREVANTTM received U.S. Food and Drug Administration (FDA) approval for patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, based on data showing an ORR of 40 percent (95 percent CI, 29 – 51) and median duration of response of 11.1 months (95 percent CI, 6.9 – NE).7

“While the recent FDA approval of RYBREVANT was an important milestone for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations, there continues to be a lack of long-term treatment options for patients with other mutations, including MET exon 14 skipping mutations,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. “We are encouraged by these data showing evidence that RYBREVANTTM can lead to broad activity against both EGFR and MET-driven tumors.”

RYBREVANTTM (amivantamab-vmjw) received accelerated approval by the U.S. FDA 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 in May 2021.7 Janssen has filed regulatory submissions for RYBREVANTTM with health authorities in Europe and other markets. RYBREVANTTM is being studied in multiple clinical trials, including a Phase 1/1b study, CHRYSALIS-2 (NCT04077463) to examine the combination 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, amivantamab, carboplatin-pemetrexed vs. with 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 RYBREVANTTM in combination with carboplatin-pemetrexed for 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 RYBREVANTTM based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for RYBREVANTTM SC delivery.8,9,10,11,12 

**In 2018, Janssen Biotech, Inc. entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

About the CHRYSALIS Study
CHRYSALIS (NCT02609776) is a Phase 1 open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics and preliminary efficacy of RYBREVANTTM as a monotherapy and in combinations including with lazertinib, a novel third-generation EGFR TKI13, in adults with advanced NSCLC.12 The study consists of two parts: RYBREVANTTM monotherapy and combination-dose escalations and RYBREVANTTM monotherapy and combination-dose expansions.12 

About Non-Small Cell Lung Cancer (NSCLC)
Worldwide, lung cancer is one of the most common cancers, and NSCLC makes up 80 to 85 percent of all lung cancers.14,15 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.16 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.16 EGFR mutations are present in 10 to 15 percent17,18,19,20,21 of people with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asians.22,23 METex14 mutations are found in approximately three percent of patients with NSCLC.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, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology and Pulmonary Hypertension.

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

[1] Spira et al. Amivantamab in Non-small Cell Lung Cancer (NSCLC) with MET Exon 14 Skipping (METex14) Mutation: Initial Results from CHRYSALIS. IASLC 2021 WCLC.
[2] Frampton Cancer Discov 5:850;
[3] DeMello et al. The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer. J Clin Med. 2020 Jun; 9(6): 1918.
[4] Capmatinib Prescribing Information 2020
[5] Tepotinib Prescribing Information 2020
[6] Recondo, G et al. Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14–Mutant NSCLC. Clinical Cancer Research. 2020. 26 (11): 2615-2625.
[7] RYBREVANTTM Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
[8] 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 August 2021.
[9] 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). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664?term=PAPILLON&cond=NSCLC&draw=2&rank=1. Accessed August 2021.
[10] ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies. Available at: https://clinicaltrials.gov/ct2/show/NCT04606381. Accessed August 2021.
[11] ClinicalTrials.gov. Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer. Available at: https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed August 2021.
[12] 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). https://clinicaltrials.gov/ct2/show/NCT04988295. Accessed August 2021.
[13] Ahn, J. et al. Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: results from the dose escalation and dose expansion parts of a first-in-human, open-label, multicentre, phase 1–2 study. Lancet Oncology. 2019. 20 (12):  1681-1690.
[14] The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed August 2021.
[15] American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed August 2021.
[16] Remon, J et al. EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins. Cancer Treatment Reviews. 90 (2020).
[17] 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.
[18] Bauml, JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. WCLC Poster #3399. January 2021.
[19] Riess JW, Gandara DR, Frampton GM, 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
[20] 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. J Clin Oncol. 37:97-104.
[21] Burnett H, Emich H, Carroll C, Stapleton N, Mahadevia P, Li T. 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.
[22] Zhang et al 2016 (Oncotarget, Vol. 7, No. 48) study which estimated prevalence of EGFR mutations across various patient subgroups, including Asians.
[23] Midha 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

SOURCE: Janssen