Janssen: New Amivantamab Data from CHRYSALIS Study Show Robust Clinical Activity and Durable Responses in Patients with Metastatic or Unresectable Non-Small Cell Lung Cancer and EGFR Exon 20 Insertion Mutations

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The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new data from the Phase 1 CHRYSALIS study, which evaluated amivantamab in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease progressed on or after platinum-based chemotherapy.¹ These data were presented for the first time in an oral presentation at the International Association for the Study of Lung Cancer’s (IASLC) 2020 World Conference on Lung Cancer (WCLC) Singapore. The key findings showed robust activity and durable responses with a tolerable and manageable safety profile (Abstract #3031) in patients with NSCLC and EGFR exon 20 insertion mutations, a mutation for which no targeted therapies are currently approved.^1,2,3

Amivantamab is an investigational, fully-human EGFR and MET bispecific antibody with immune cell-directing activity that targets tumours with activating and resistance EGFR and MET mutations and amplifications.^4,5,6,7 Janssen has filed regulatory submissions in Europe and the U.S. seeking approval of amivantamab for the treatment of patients with NSCLC and EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.^8,9 These applications mark the first-ever regulatory submissions for a treatment for patients with NSCLC and EGFR exon 20 insertion mutations.¹⁰

“There is a significant need for new treatment options for patients with NSCLC and EGFR exon 20 insertion mutations whose disease generally does not respond well to chemotherapy and the tyrosine kinase inhibitors used to treat other EGFR mutations,” said Joshua K. Sabari, M.D., New York University Langone’s Perlmutter Cancer Centre and presenting investigator. “Results from the CHRYSALIS study presented today demonstrate the potential for amivantamab to address this critical unmet need and provide an important clinical benefit to patients.”

In this analysis of the Phase 1 CHRYSALIS study, investigators assessed the efficacy and safety of amivantamab in patients with NSCLC and EGFR exon 20 insertion mutations, who had progressed on prior platinum-based chemotherapy, and were treated at the recommended Phase 2 dose (RP2D of 1050 mg [1400 mg for a patient weight of ≥80 kg] amivantamab).¹ Disease response using overall response rate (ORR), per Response Evaluation Criteria in Solid Tumours Version 1.1* (RECIST v1.1) was the primary endpoint.¹ Other endpoints included duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS).^1,11 In the post-platinum efficacy cohort (n=81), the ORR as assessed by blinded independent central review was 40 percent (n=32; 95 percent CI, 29 – 51), with three patients (4 percent) having complete responses and 29 patients (36 percent) achieving partial responses (PR).¹ Responses were durable with median duration of response of 11.1 months (95 percent CI, 6.9 – not reached), with 63 percent (n=20/32) having responses of at least six months or greater duration.¹ Median PFS was 8.3 months (95 percent CI, 6.5 – 10.9) and median overall survival was 22.8 months (95 percent CI, 14.6 – not reached).¹ The clinical benefit rate (≥PR or stable disease ≥11 weeks) was 74 percent (95 percent CI, 63 – 83).¹

Among patients treated with amivantamab monotherapy (n=114) at the RP2D, the most common treatment-emergent adverse events (AEs) were rash (86 percent), infusion-related reactions (IRR; 66 percent) and paronychia (45 percent).¹ Additional AEs were stomatitis (21 percent) and pruritus (17 percent).¹ Grade ≥3 AEs were reported in 35 percent of patients, of which 16 percent were considered treatment-related with rash (4 percent) and IRR (3 percent) being most frequent.¹ No treatment-related deaths were reported.¹ The incidence of treatment-related AEs leading to dose reduction and discontinuation was 13 percent and 4 percent, respectively.¹

“The data presented today further demonstrates the potential of amivantamab as a targeted therapy for a patient population which harbours a very resistant mutation and urgently needs new therapeutic options,” said Joaquín Casariego, M.D., Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag, S.A. “We are committed to exploring further the role this innovation may have in addressing the unmet needs for many more patients and their families.”

EGFR mutations, leading to uncontrolled cancer cell growth and division,¹² are some of the most common mutations in NSCLC.¹³ EGFR exon 20 insertion mutations are the third most prevalent primary EGFR mutation and account for 3.7 – 10 percent of all EGFR mutations.^3,14 These mutations, however, often go undetected because of the limited use of Next Generation Sequencing (NGS) testing.^2,15 Additional Janssen-sponsored data presented in a featured poster at WCLC (Abstract #3399) showed that polymerase chain reaction (PCR) genetic testing is projected to miss 50 percent or more of tumours with EGFR exon 20 mutations.¹⁶

A Janssen-sponsored mini oral presentation at WCLC (Abstract #3390) highlights the need for new treatments, as cancer driven by EGFR exon 20 insertion mutations is generally insensitive to approved EGFR tyrosine kinase inhibitor (TKI) treatments and carries a worse prognosis compared with cancer driven by more common EGFR mutations, including exon 19 deletions/L858R substitutions.¹⁷ After 34 months median follow-up, patients with EGFR exon 20 insertion mutations experienced a 75 percent increased risk of death. The study also found that the five-year survival rate for exon 20 insertion mutations is 8 percent compared to 19 percent for other EGFR mutations.¹⁷

Janssen submitted a Marketing Authorisation Application (MAA) for amivantamab to the European Medicines Agency (EMA) in December 2020.⁹ The clinical development programme for amivantamab in untreated advanced EGFR-mutated NSCLC includes the Phase 3 MARIPOSA and PAPILLON combination trials.^18,19

*RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumours, which is a standard way to measure how well solid tumours respond to treatment and is based on whether tumours shrink, stay the same, or get bigger.²⁰

About the Phase 1 CHRYSALIS Study²¹

CHRYSALIS (NCT02609776) is an open-label, multicentre, first-in-human study to evaluate the safety, pharmacokinetics and preliminary efficacy of amivantamab as a monotherapy and in combinations including lazertinib or chemotherapy for the treatment of NSCLC.** The study will enrol 460 patients with advanced NSCLC. The study consists of two parts. The first part consists of amivantamab monotherapy and combination dose escalations and the second part is amivantamab monotherapy and combination dose escalations and expansions.

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

About Amivantamab

Amivantamab is an investigational, fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumours with activating and resistance EGFR mutations and MET mutations and amplifications.^4,5,6,7 Amivantamab is being studied as a monotherapy in patients with EGFR exon 20 insertion mutations. Amivantamab is also being studied in combination with lazertinib, a third-generation TKI,²² in adult patients with advanced NSCLC.²¹ The production and development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody^® technology platform.

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.^23,24 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.²⁵ The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.²⁶ Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.¹² EGFR mutations are present in 10 to 15 percent of patients with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asian patients.²⁷ The five-year survival rate for all patients with metastatic NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.^28,29 Estimated median overall survival for patients with NSCLC and EGFR exon 20 insertion mutations is shorter than in patients with exon 19 deletions or L858R substitutions.²⁸

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. Janssen Research & Development, LLC; Janssen-Cilag, S.A.; and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

# # #

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 materialise, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC or 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 behaviour 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.

CP-201225

Date of prep: January 2021

References:

¹ Sabari, J. et al. Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-Small Cell Lung Cancer. WCLC Oral Presentation #3031. January 2021.

² Riess JW, Gandar DR, Frampton GM, et al. Diverse EGFR Exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. J Thorac Oncolo. 2018;13(10):1560-1568. 10.1016/j.jtho.2018.06.019.

³ Vyse, S., Huang, P.H. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Sig Transduct Target Ther 4, 5 (2019).

⁴ Grugan et al. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells MAbs. 2017;9(1):114-126.

⁵ Moores et al. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res. 2016;76(13)(suppl 27216193):3942-3953.

⁶ Yun et al. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR–MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion–Driven NSCLC. Cancer Discov. 2020;10(8):1194-1209.

⁷ Vijayaraghavan et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther. 2020;19(10):2044-2056.

⁸ Janssen Submits Application to U.S. FDA Seeking Approval of Amivantamab for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. https://www.jnj.com/janssen-submits-application-to-u-s-fda-seeking-approval-of-amivantamab-for-the-treatment-of-patients-with-metastatic-non-small-cell-lung-cancer-with-egfr-exon-20-insertion-mutations. Accessed January 2021.

⁹ Janssen Submits European Marketing Authorisation Application for Amivantamab for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. https://www.janssen.com/janssen-submits-european-marketing-authorisation-application-amivantamab-treatment-patients. Accessed January 2021.

¹⁰ Remon, J et al. EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins. Cancer Treatment Reviews. 90 (2020).

¹¹ Park, K. et al. Amivantamab, an Anti-EGFR-MET Bispecific Antibody, in Patients with EGFR Exon 20 Insertion-Mutated NSCLC. https://meetinglibrary.asco.org/record/184802/abstract. Accessed January 2021.

¹² Wee,P, Wang, Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers (Basel). 2017 May; 9(5): 52.

¹³ Hong, W. et al. Prognostic value of EGFR 19-del and 21-L858R mutations in patients with non-small cell lung cancer. Oncol Lett. 2019 Oct; 18(4): 3887–3895.

¹⁴Crossland V et al. HSR19-082: Epidemiological Findings and Outcomes in Non-Small Cell Lung Cancer Patients with Exon 20 Insertion Mutations: A Meta-Analysis. JNCCN 2019; 17(3.5): HSR19-08..

¹⁵ Feng Y et al. Exploratory analysis of introducing next-generation sequencing-based method to treatment-naive lung cancer patients J Thorac Dis 2018; 10(10): 5904–5912

¹⁶ Baumi, JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. WCLC Poster #3399. January 2021.

¹⁷ Girard N. et al. Comparative Clinical Outcomes for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations. WCLC Mini-Oral Presentation #3390. January 2021.

¹⁸ 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 January 2021.

¹⁹ 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 January 2021.

²⁰ Eisenhauer E.A. et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal of Cancer. 2009. 45: 228 – 247

²¹ 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 January 2021.

²² 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.

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²⁷ Zhang 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

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²⁹ Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). 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.

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