RARITAN, N.J., Sept. 20, 2020 /PRNewswire/ -- The Janssen
Pharmaceutical Companies of Johnson & Johnson today announced
interim results from the CHRYSALIS study (NCT02609776), evaluating
amivantamab, a fully human bispecific antibody that targets
epidermal growth factor receptor (EGFR) and mesenchymal epithelial
transition factor (MET) mutations1, in combination with
the third-generation EGFR tyrosine kinase inhibitor (TKI)
lazertinib2 in patients with non-small cell lung
cancer (NSCLC) with EGFR exon 19 deletions or L858R mutations.
Investigators assessed efficacy using overall response rate (ORR)
per Response Evaluation Criteria in Solid Tumors Version 1.1
(RECIST v1.1), clinical benefit rate, duration of response and the
safety profile of amivantamab and lazertinib,3 in
the 91 patients treated with the combination across dose escalation
and expansion cohorts3. The study results were presented
at the European Society for Medical Oncology (ESMO) Virtual
Congress 2020 (Abstract #1258O) as an oral
presentation3. Results from the CHRYSALIS study have led
to new studies to further evaluate the potential of amivantamab and
lazertinib combination therapy.4
The CHRYSALIS study is an open-label, global, multi-center study
evaluating the safety, pharmacokinetics and efficacy of amivantamab
as a monotherapy and in combination with lazertinib in adult
patients with advanced NSCLC.5 Exon 19 deletion and
L858R mutations are common, accounting for 85-90 percent of all
EGFR mutations in NSCLC.6 In the study, 91 patients
with NSCLC harboring EGFR exon 19 deletion or L858R mutations
received the combination of amivantamab intravenously and
lazertinib orally.3 The study enrolled 26 patients
in dose escalation and identified a combination dose that was
equivalent to monotherapy doses of both products.3
Additionally, 20 treatment-naïve patients with EGFR-mutated NSCLC
were enrolled to further examine the safety, efficacy and
tolerability in the first-line setting and 45 patients who had
relapsed on osimertinib but were chemotherapy-naïve were enrolled
to examine safety and efficacy in the resistance
setting.3
In the treatment-naïve group, 20 patients receiving the
combination of amivantamab and lazertinib achieved a 100 percent
ORR (95 percent CI, 83 – 100).3 The median
follow-up and treatment duration at the time of data cut-off was
seven months (3 – 10).3 Among 45
osimertinib-relapsed, chemotherapy-naïve patients, the combination
of amivantamab and lazertinib resulted in a 36 percent ORR (95
percent CI, 22 – 51), with one complete response and 15 partial
responses.3 The clinical benefit rate for these
patients was 60 percent (95 percent CI; 44 –
74).3 Biomarker and central nervous system analyses
and efficacy by mechanism of osimertinib resistance are ongoing and
will be presented at a future medical meeting.
"Despite treatment advancements, lung cancer remains the leading
cause of cancer deaths globally, and there are opportunities to
improve treatment options for patients with non-small cell lung
cancer with genetic factors such as EGFR mutations," said
Byoung Chul Cho, M.D., Ph.D., Yonsei
Cancer Center, Yonsei University
College of Medicine in Seoul, South
Korea, and lead study investigator. "We are encouraged by
these results that suggest amivantamab in combination with
lazertinib may be a promising option in this specific disease
cohort where a high unmet need remains for more targeted treatment
options."
For the 91 treated patients, the majority of treatment-related
adverse events (AEs) experienced were Grade 1-2.3 A
low incidence of Grade ≥3 treatment-related AEs occurred, which
included rash (four percent), hypoalbuminemia (two percent),
increased gamma glutamyltransferase (one percent), hyponatremia
(one percent), paronychia (one percent) and interstitial lung
disease (one percent) were observed.3 Related AEs
leading to treatment discontinuation occurred in six percent of
patients.3 Infusion-related reaction occurred
predominantly at first infusion and did not impact subsequent
dosing.3
The results from the CHRYSALIS study have led to new studies to
further evaluate the potential of amivantamab and lazertinib
combination therapy. The Phase 3 MARIPOSA study (NCT04487080) will
assess the amivantamab and lazertinib combination against
osimertinib in untreated advanced EGFR-mutated
NSCLC,4 and Phase 2 trial, CHRYSALIS-2,
(NCT04077463) has been initiated to examine the combination in
patients who have progressed after treatment with osimertinib and
chemotherapy.7
"We are committed to advancing our understanding of the biology
of lung cancer in order to develop targeted therapies that address
specific patient populations, such as those with EGFR-mutated
non-small cell lung cancer," said Kiran
Patel, M.D., Vice President, Clinical Development, Solid
Tumors, Janssen Research & Development, LLC. "We are proud to
present the results from this study and look forward to the
continued evaluation of the amivantamab and lazertinib combination
in these patients."
About Amivantamab
Amivantamab, formerly
JNJ-61186372, is an investigational EGFR-MET bispecific antibody
with immune cell-directing activity that targets activating and
resistance EGFR mutations and MET mutations and
amplifications.3,5 In
March 2020, amivantamab
received Breakthrough Therapy Designation from the U.S.
Food and Drug Administration (FDA) for the treatment of patients
with metastatic NSCLC with EGFR exon 20 insertion mutations whose
disease has progressed on or after platinum-based
chemotherapy.8 These results were also
presented at the American Society of Clinical Oncology (ASCO)
2020 Scientific Program. The production and development of the
antibody followed Janssen Biotech, Inc.'s licensing agreement with
Genmab for use of its DuoBody® technology platform.
About Lazertinib
Lazertinib is an oral,
third-generation, brain-penetrant, EGFR TKI that targets both the
T790M mutation and activating EGFR mutations while sparing wild
type-EGFR.9 Interim safety and efficacy results
from the lazertinib Phase 1-2 study were published in The Lancet
Oncology in 2019. In 2018, Janssen Biotech, Inc.
entered into a license and collaboration agreement with Yuhan
Corporation for the development of lazertinib.
About Non-Small Cell Lung Cancer (NSCLC)
Worldwide,
lung cancer is the most common cancer, and NSCLC makes up 80-85
percent of all lung cancers.10,11
The main subtypes of NSCLC are adenocarcinoma, squamous cell
carcinoma and large cell carcinoma.12 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 patients with NSCLC and occur in 40 to 50 percent of
Asian patients who have NSCLC
adenocarcinoma.14,15,16 The five-year
survival rate for patients with metastatic NSCLC is currently 24
percent.17
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
www.twitter.com/JanssenGlobal and www.twitter.com/JanssenUS.
Janssen Research & Development, LLC 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 and lazertinib. 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, 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 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.
1 Suurs, F. et al. A review of bispecific
antibodies and antibody constructs in oncology and clinical
challenges. Pharmacology & therapeutics 201 (2019) 103-119.
2 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.
3 Chul Cho, B. et al. Amivantamab (JNJ-61186372),
an EGFR-MET bispecific antibody, in combination with lazertinib, a
3rd-generation tyrosine kinase inhibitor (TKI), in advanced EGFR
NSCLC. Available
at: https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/amivantamab-jnj-61186372-an-egfr-met-bispecific-antibody-in-combination-with-lazertinib-a-3rd-generation-tyrosine-kinase-inhibitor-tki-in-a.
4 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?term=JNJ-61186372&draw=2&rank=3.
Accessed September 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. Accessed
September 2020.
6 Wong, 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.
7 Clinicaltrials.gov. A Study of Lazertinib as
Monotherapy or in Combination With JNJ-61186372 in Participants
With Advanced Non-small Cell Lung Cancer. Available at:
https://www.clinicaltrials.gov/ct2/show/record/NCT04077463?view=record.
Accessed September 2020.
8 Janssen Announces U.S. FDA Breakthrough Therapy
Designation Granted for JNJ-6372 for the Treatment of Non-Small
Cell Lung Cancer. Available
at: 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.
Accessed September 2020.
9 Clinicaltrials.gov. Clinical Trial of YH25448 in
Patients With EGFR Mutation Positive Advanced NSCLC. Available
at: https://clinicaltrials.gov/ct2/show/NCT03046992. Accessed
September 2020.
10 The World Health Organization. Cancer. Available
at: https://www.who.int/news-room/fact-sheets/detail/cancer.
Accessed September 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.
Accessed September 2020.
12 Wee,P, Wang, Z. Epidermal Growth Factor Receptor
Cell Proliferation Signaling Pathways. Cancers (Basel). 2017 May; 9(5): 52.
13 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.
14 Pao W, Girard N. New driver mutations in
non-small-cell lung cancer. Lancet Oncol. 2011;12(2):175-180.
15 Zappa C, Sharker M. Non-small cell lung cancer:
current treatment and future advances. Translational Lung Cancer
Research. 2016 Jun; 5(3): 288–300.
16 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.
17 Cancer.net. Lung Cancer - Non-Small Cell:
Statistics. Available
at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed September 2020.
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