On January 28, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported 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 (Press release, Johnson & Johnson, JAN 28, 2021, View Source [SID1234574392]).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

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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