RARITAN - The Janssen Pharmaceutical Companies of
These data were presented for the first time in an oral presentation at the
Amivantamab is an investigational, fully-human EGFR and MET bispecific antibody with immune cell-directing activity that targets tumors with activating and resistance EGFR and MET mutations and amplifications.4,5,6,7 Janssen has filed regulatory submissions in the
'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
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 Tumors Version 1.1 (RECIST v1.1) was the primary endpoint.1 Other endpoints included duration of response (DOR), clinical benefit rate, progression-free survival (PFS) and overall survival (OS).1,10 In the post-platinum efficacy cohort (n=81), the ORR as assessed by blinded independent central review was 40 percent (n=32; 95 percent confidence interval (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 20 patients (63 percent) 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 OS 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
'These encouraging results further underscore the potential of amivantamab as a targeted therapy for patients with NSCLC and EGFR exon 20 insertion mutations,' said
EGFR mutations, leading to uncontrolled cancer cell growth and division11, are some of the most common mutations in NSCLC.12 EGFR exon 20 insertion mutations are the third most prevalent primary EGFR mutation and account for at least nine percent of all EGFR mutations.13 These mutations, however, often go undetected because of the limited use of Next Generation Sequencing (NGS) testing.6,12 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 tumors with EGFR exon 20 mutations.14
A 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.7,15 After 34-months median follow-up, patients with EGFR exon 20 insertion mutations experienced a 75 percent increased risk of death.15 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.15
Amivantamab received Breakthrough Therapy Designation from the
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.19
About the Phase 1 CHRYSALIS Study
CHRYSALIS (NCT02609776) is an open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics and preliminary efficacy of amivantamab as a monotherapy and in combinations including lazertinib. The study will enroll 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
About Amivantamab
Amivantamab is an investigational, fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumors with activating and resistance EGFR mutations and MET mutations and amplifications.4,5,6,7 Companion diagnostics using NGS, which are necessary to identify patients with EGFR exon 20 insertion mutations, have been an integral part of the development program for amivantamab. 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 TKI20, in adult patients with advanced NSCLC.21 The production and development of the antibody followed
About the Amivantamab Expanded Access Program (EAP) Protocol
The amivantamab EAP is for
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.22,23 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.24 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.11 EGFR mutations are present in 10 to 15 percent of patients with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asian patients.24 The five-year survival rate for all patients with metastatic NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.25,26 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.25
About the Janssen Pharmaceutical Companies of
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of
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
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