Genosco, a clinical-stage biotechnology company focused in immunology
and oncology, announced data from a Phase 1/2 study evaluating
lazertinib (YH25448, GNS-1480) in patients with advanced Non-Small Cell
Lung Cancer (NSCLC) at the 2018 American
Society of Clinical Oncology (ASCO) Annual Meeting. Lazertinib
(YH25448, GNS-1480), Genosco’s 3rd-generation EGFR-tyrosine kinase
inhibitor (EGFR-TKI) candidate partnered for clinical development and
commercialization with Yuhan Corporation, is an oral, potent,
irreversible EGFR-TKI that is highly selective for activating (EGFRm)
and T790M resistance mutations.
This press release features multimedia. View the full release here:
https://www.businesswire.com/news/home/20180603005046/en/
ASCO Abstract 9033 Infographic (Graphic: Business Wire)
Results
from the open-label, multi-center dose-escalation, Phase 1/2 study of
lazertinib (YH25448, GNS-1480) for patients with advanced
EGFR-TKI-resistant NSCLC with or without CNS metastasis concluded that
lazertinib was well-tolerated with low rates of Grade 3 or higher
adverse events (AE) and exhibited robust activity in patients with NSCLC
with acquired resistance to EGFR-TKIs, with or without brain metastasis.
Principal Investigator Byoung Chul Cho, M.D., Ph.D., Division of Medical
Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei
University College of Medicine, Seoul, Republic of Korea presented the
data in a poster session (Abstract
9033).
“These data are impressive and underscore the potential of lazertinib
(YH25448, GNS-1480) to be the best-in-class 3rd-generation EGFR-TKI for
patients with advanced EGFR T790M mutant NSCLC, including brain
metastasis. And importantly, the treatment was well-tolerated with no
dose-limiting toxic effects,” said Dr. Byoung Chul Cho. “Results
indicate that lazertinib compares favorably with results from a similar
Phase 1/2 clinical trial of osimertinib (AURA)1,
a currently marketed 3rd generation EGFR-TKI.”
“The efficacy signals and safety profiles are highly encouraging and
validate lazertinib (YH25448, GNS-1480) as a promising 3rd-generation
EGFR-TKI inhibitor for patients with limited options,” said Jong Sung
(John) Koh, Ph.D., Genosco CEO. “Yuhan and Genosco initiated a global
Phase 2 trial evaluating lazertinib for patients with NSCLC and
anticipate a global Phase 3 trial in 2019.”
“These results confirm our belief that recently presented pre-clinical
data at AACR2
may translate into human studies,” said Ho-Juhn Song,
Ph.D., Director of Biology and Strategic Alliance of Genosco. “The
comparative analyses of lazertinib and osimertinib concluded that
lazertinib showed greater potency and selectivity, excellent
intracranial penetration, superior in vivo efficacy in both single
(del19, L858R) and double (L858R/T790M) mutant xenograft models and
superior in vivo efficacy in a brain metastasis model.”
Study results:
A total of 118 patients [dose-escalation cohort (n=38) and expansion
cohort (n=80)] with EGFRm advanced NSCLC with acquired resistance to
EGFR-TKIs with or without brain metastasis were enrolled in the Phase
1/2 study as of April 20, 2018.
The results demonstrate that lazertinib (YH25448, GNS-1480) has a good
safety profile and was generally well-tolerated. No dose-limiting
toxicities were observed up to lazertinib 320mg and there were no
dose-dependent increases in treatment-emergent adverse events (TEAEs).
Of the evaluable patients (n=110) with a confirmed response at the date
of data cutoff, lazertinib (YH25448, GNS-1480) demonstrated promising
anti-tumor efficacy signals with a confirmed objective response rate
(ORR) of 61% across all dose levels. Of note, the confirmed ORR in
patients with T790M+ was 86% at the lazertinib 240mg dose level and in
patients with brain metastasis, the intracranial ORR was 55% across all
dose levels.
Key findings include:
Anti-tumor efficacy – all confirmed responses
|
Overall Objective Response Rate (ORR) – all doses
|
|
(n=110)
|
|
61%
|
ORR - T790M-positive patients – all doses
|
|
(n=92)
|
|
66%
|
ORR - T790M-positive patients – 240 mg dose
|
|
(n=7)
|
|
86%
|
ORR - T790M-negative patients – all doses
|
|
(n=18)
|
|
33%
|
ORR – patients with brain metastasis
|
|
(n=11)
|
|
55%
|
Tolerability (Adverse Event)
|
Any AEs of grade 3-5
|
|
11%
|
Any drug-related AEs grade 3-5
|
|
2%
|
|
|
|
EDITORS NOTE: An infographic accompanying this release is available.
Sources:
1 N
Engl J Med 372;18 nejm.org April 30, 2015; AZD9291 in EGFR
Inhibitor–Resistant Non–Small-Cell Lung Cancer.
2
AACR
2018 Annual Meeting Abstract Number 4790: YH25448, an irreversible
3rd-generation EGFR TKI, exhibits superior anticancer effects with
potent brain BBB penetration in NSCLC.
About Lazertinib
Lazertinib (YH25448, GNS-1480) is an oral, potent, highly
mutant-selective and irreversible, investigational 3rd-generation
EGFR-TKI that penetrates the blood-brain barrier (BBB). It targets the
activating EGFR mutations Del19 and L858R, as well as the T790M
mutation, while sparing wild type. EGFR mutations are present in
approximately 10-15% of NSCLCs. Lazertinib is being evaluated in
advanced NSCLC as both first- and second-line treatments.
About Genosco
Located in Cambridge, MA, Genosco is a clinical-stage biotechnology
company led by CEO, Dr. Jong Sung (John) Koh, focusing on developing and
commercializing novel immunology and oncology treatments to improve the
lives of patients. Genosco’s core competence comes from its expertise in
generating selective kinase inhibitors that include candidates that
target EGFRm+ (NSCLC), SYK (Autoimmune diseases) and FLT3/AXL (AML) and
other conditions. The company is enrolling patients in a Phase 1 study
of SKI-G-801 for AML and expects to initiate a Phase 2 study of
SKI-O-703 in ITP and RA in 2018. In 2015, Genosco partnered globally
with Yuhan Corporation for development and commercialization of
lazertinib (YH25448, GNS-1480), a 3rd-generation EGFR-TKI, for treatment
of NSCLC currently in Phase 2 clinical trials. Genosco was founded in
2008 as a subsidiary company of Oscotec, Inc, (KOSDAQ: 039200), South
Korea. For more information, please visit www.genosco.com.
About Yuhan Corporation
Yuhan Corporation is a globally operating, leading pharmaceutical
company in South Korea led by CEO Jung Hee Lee. Founded in 1926 by Dr.
Ilhan New, the company is engaged in research and development (R&D),
drug manufacturing, CMO business, marketing and distribution of a broad
spectrum of pharmaceutical and healthcare products. R&D strategies of
Yuhan Corporation revolve around, first and the foremost, the patient
needs. This patient-centered approach has directed the focus of Yuhan
R&D on two critical areas of unmet medical needs; oncology and metabolic
diseases. For more information, please visit www.yuhan.co.kr.
Source: Genosco
View source version on businesswire.com: https://www.businesswire.com/news/home/20180603005046/en/