Janssen Announces Phase 1 Results for Bispecific Antibody Amivantamab in the Treatment of Patients with Advanced Non-Small Cell Lung Cancer Harbouring Exon 20 Insertion Mutations

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 1 CHRYSALIS study evaluating amivantamab (JNJ-6372) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations.¹ Amivantamab is an EGFR and MET-targeted bispecific antibody, which targets activating and resistance EGFR mutations, and MET pathway activation.^2,3 Investigators assessed efficacy using overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), duration of response, as well as the safety profile of amivantamab,¹ which were the basis of the U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation granted earlier this year.⁴

The Phase 1 CHRYSALIS study is a first-in-human, open-label, multi-cohort, multicentre study evaluating the safety, pharmacokinetics and efficacy of amivantamab as a monotherapy and in combination with lazertinibⁱ, a novel third-generation EGFR tyrosine kinase inhibitor (TKI), in adult patients with advanced NSCLC.⁵ Fifty patients with EGFR Exon 20 insertion-mutated NSCLC received the recommended Phase 2 dose (RP2D) of amivantamab.¹ Among these 50 patients, 39 were evaluable for response with 13 distinct EGFR Exon 20 insertion mutations identified.¹ Detailed results will be presented as a poster presentation and discussion at the American Society of Clinical Oncology (ASCO) Virtual Scientific Programme (Abstract #9512) beginning Friday 29^th May.

Patients with NSCLC and EGFR Exon 20 insertion mutations have a form of disease that is generally insensitive to approved EGFR TKI treatments and as a result carries a worse prognosis compared to patients with more common EGFR mutations (Exon 19 deletions/L858R substitution).⁶ Currently, there are no targeted therapies approved specifically for patients with lung cancer who have EGFR Exon 20 insertion mutations.⁷ Estimated median overall survival for patients with NSCLC and Exon 20 insertion mutations is 16 months.⁸

“Lung cancer is the leading cause of cancer deaths worldwide, and genetic factors such as EGFR mutations can have a significant impact on the development and progression of non-small cell lung cancer,”said Keunchil Park, M.D., Ph.D., Professor, Division of Haematology-Oncology, Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine in Seoul, South Korea, and lead study investigator. “We look forward to sharing these data that provide initial insights into the potential of amivantamab as a treatment option for patients with non-small cell lung cancer and EGFR Exon 20 insertion mutations who have a high unmet need and often do not respond to the current standard of care.”

Findings from the study showed an ORR of 36 percent (95 percent CI, 21–53) in all evaluable patients and 41 percent (95 percent CI, 24–61) in the 29 evaluable patients previously treated with platinum-based chemotherapy.¹ Additionally, the median duration of response for all evaluable patients was 10 months and seven months for patients previously treated with platinum-based chemotherapy.¹ The median progression-free survival was 8.3 months (95 percent CI, 3.0–14.8) for all evaluable patients and 8.6 months (95 percent CI, 3.7–14.8) for patients previously treated with platinum-based chemotherapy.¹ The clinical benefit rate (partial response or better or stable disease of at least 12 weeks [two disease assessments]) was 67 percent (95 percent CI, 50–81) for all evaluable patients and 72 percent (95 percent CI, 53–87) for patients previously treated with platinum-based chemotherapy.¹ Responses were observed in both treatment-naive patients and those previously treated with platinum-based chemotherapy.¹ Tumour responses were most frequently observed at the first disease assessment after starting therapy.¹

The most common all-grade adverse events (AE) were rash, infusion-related reaction (IRR), and paronychia.¹ IRRs occurred predominantly on the first infusion and did not prevent subsequent treatments.¹ No grade ≥3 rash was reported, and one patient reported grade 3 diarrhoea and six percent had diarrhoea of any grade.¹ Six percent had treatment-related grade ≥3 AEs of hyperamylasaemia, hypokalaemia, increased lipase and shoulder/chest pain.¹ Treatment-related serious AEs of cellulitis, interstitial lung disease and shoulder/chest pain were reported in six percent of patients.¹ Additional EGFR-related AEs included stomatitis (sixteen percent), pruritus (fourteen percent), and diarrhoea (six percent).¹

“Despite years of research and the availability of more treatment options, lung cancer remains Europe’s biggest cancer death threat,” said Dr Joaquín Casariego, M.D., Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. “It is vital that we develop new, innovative, targeted treatments to improve outcomes for patients with this aggressive cancer. The initial data presented today provides encouraging insights on the potential of amivantamab in non-small cell lung cancer bearing Exon 20 insertion mutations, and we are committed to exploring further the role this innovation may have in addressing the unmet needs for many more patients, their families and the medical community.”

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About Amivantamab
Amivantamab (JNJ-6372) is an investigational EGFR-MET bispecific antibody with immune cell-directing activity, which targets activating and resistance EGFR mutations, and MET pathway activation.^2,3 The production and development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody^® technology platform.⁹

About Non-Small Cell Lung Cancer (NSCLC)
In Europe, it is estimated that over 470,000 patients were diagnosed with lung cancer in 2018, with around 85 percent diagnosed with NSCLC.^10,11 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.¹⁰ The five-year survival rate for patients with metastatic NSCLC is currently 24 percent.¹²

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.¹³ Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase that helps cells grow and divide.¹³ EGFR mutations are present in 10 to 15 percent of Caucasian patients with NSCLC and occur in 40 to 50 percent of Asian patients who have NSCLC adenocarcinoma.^12,14,15 EGFR Exon 20 insertion mutations identify a distinct subset of lung adenocarcinomas, accounting for four to nine percent of all EGFR mutations.¹⁶

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/emea. Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen Research & Development, LLC, Janssen-Cilag S.A. and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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DuoBody^® is a registered trademark of Genmab A/S.

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 amivantamab. 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 & Development, LLCor 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 December 29, 2019, 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 forward-looking statement as a result of new information or future events or developments.

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

References
¹ Park, K. et al. Amivantamab, an Anti-EGFR-MET Bispecific Antibody, in Patients with EGFR Exon 20 Insertion-Mutated NSCLC. Available at: https://meetinglibrary.asco.org/record/184802/abstract. Last accessed May 2020.
² Suurs, F. et al. A review of bispecific antibodies and antibody constructs in oncology and clinical challenges. Pharmacology & Therapeutics. 201 (2019) 103-119.
³ Moores SL, Chiu ML, Bushey BS, et al. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res. 2016;76(13):3942-3953.
⁴ Janssen Announces U.S. FDA Breakthrough Therapy Designation Granted for JNJ-6372 for the Treatment of Non-Small Cell Lung Cancer. https://www.jnj.com/janssen-announces-u-s-fda-breakthrough-therapy-designation-granted-for-jnj-6372-for-the-treatment-of-non-small-cell-lung-cancer. Last accessed May 2020.
⁵ 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. Last accessed May 2020.
⁶ Vyse, S. Huang, P.H. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Sig TransductTarget Ther. (2019); 4:5.
⁷ Baraibar, I. et al. Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Critical Reviews in Oncology/Haematology. 2020. Volume 148. 102906.
⁸ 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.
⁹ Genmab.com. Genmab Enters Broad Collaboration with Janssen Biotech, Inc. for DuoBody Platform. Available at: https://ir.genmab.com/news-releases/news-release-details/genmab-enters-broad-collaboration-janssen-biotech-inc-duobody. Last accessed May 2020.
¹⁰ Globocan 2018. Europe factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf. Last accessed May 2020.
¹¹ American Cancer Society. What is Lung Cancer? Available at: https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Last accessed May 2020.
¹² Cancer.net. Lung Cancer - Non-Small Cell: Statistics. Available at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics. Last accessed May 2020.
¹³ Wee, P, Wang, Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers (Basel). 2017 May; 9(5):52.
¹⁴ Zappa, C, Sharker, M. Non-small cell lung cancer: current treatment and future advances. Translational Lung Cancer Research. 2016 Jun; 5(3): 288–300.
¹⁵ Jänne, PA, Johnson BE. Effect of Epidermal Growth Factor Receptor Tyrosine Kinase Domain Mutations on the Outcome of Patients with Non–Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. Clinical Cancer Research. 2006;12(14):4416s–4420s.
¹⁶ 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.

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