-
Phase I/II study of
entrectinib, an investigational medicine, showed responses in all
paediatric tumour types harbouring neurotrophic tyrosine receptor
kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK) fusions,
including those in the central nervous system
-
Data featured in the ASCO
presscast on Wednesday, 15 May, and will be presented at the 2019
ASCO Annual Meeting on Sunday, 2
June
Basel, 16 May 2019 - Roche (SIX: RO, ROG; OTCQX:
RHHBY) today announced positive data from the Phase I/II STARTRK-NG
study, evaluating the investigational medicine entrectinib in
children and adolescents with recurrent or refractory solid tumours
with and without neurotrophic tyrosine receptor kinase (NTRK), ROS1
or anaplastic lymphoma kinase (ALK) gene fusions. The study showed
entrectinib shrank tumours (objective response rate; ORR) in all
children and adolescents who had NTRK, ROS1 or ALK fusion-positive
solid tumours (11 of 11 patients), including two patients achieving
a complete response.1 Of the 11
patients, five patients with primary high-grade tumours in the
central nervous system (CNS) had an objective response, including
one patient with a complete response.1 The safety
profile of entrectinib was consistent with that seen in previous
analyses.1 Data will be
presented at the American Society of Clinical Oncology (ASCO)
Annual Meeting in Chicago on Sunday, 2 June, 2019, from 8:00 - 8:12
am CDT (Abstract 10009), and was part of yesterday's official ASCO
presscast.
"We are encouraged by the results we have seen with entrectinib in
children with paediatric and adolescent cancers, including those
with tumours in the brain," said Sandra Horning, MD, Roche's Chief
Medical Officer and Head of Global Product Development. "The
STARTRK-NG study underscores the importance of combining
comprehensive genomic profiling with targeted therapies and
supports our approach to providing people with personalised
medicines developed specifically for their type of
cancer."
Additional data for entrectinib across different tumour types and
patient populations will also be presented at ASCO, highlighting
the company's unique approach to personalised healthcare through
advances in targeted therapies, diagnostics and data analytics:
-
Initial results from an integrated analysis of
the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001
trials, evaluating the efficacy of entrectinib in adults with solid
tumours and CNS metastases, will be presented on Saturday, 1 June,
2019, in a poster session from 3:00 - 4:30 pm CDT (Abstract
3017).
-
Results from a Real World Data study, evaluating
time-to-treatment discontinuation and progression-free survival as
endpoints for comparative efficacy analysis of clinical trials of
entrectinib and crizotinib for the treatment of people with
ROS1-positive non-small cell lung cancer (NSCLC), will be presented
during a poster session on Sunday, 2 June, 2019, from 8:00 - 11:00
am CDT (Abstract 9070).
The FDA recently granted Priority Review for entrectinib for both
the treatment of paediatric and adult patients with NTRK
fusion-positive, locally advanced or metastatic solid tumours who
have either progressed following prior therapies or as an initial
therapy when there are no acceptable standard therapies, and for
the treatment of people with metastatic ROS1-positive
NSCLC.2 These NDAs
are based on results from the integrated analysis of the Phase II
STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and
data from the STARTRK-NG study. The FDA is expected to make a
decision on approval by 18 August, 2019.2
About the STARTRK-NG study
STARTRK-NG is a Phase I/II open-label dose-escalation and expansion
study evaluating the safety and efficacy of entrectinib in children
and adolescent patients with no curative first-line treatment
option, recurrent or refractory extracranial solid tumours or
primary CNS tumours, with or without NTRK, ROS1 or ALK
fusions.1 Response,
assessed by Investigator, was classified as complete response (CR),
partial response (PR), stable disease (SD) or progressive disease
(PD) using Response Assessment in Neuro-Oncology (RANO) for CNS
tumours, Response Evaluation Criteria in Solid Tumors
(RECIST), and Curie
score (CS) for NBL.1 The study
enrolled 29 children and adolescents aged 4.9 months through to 20
years (median age of 7 years) who had recurrent or refractory solid
tumours, and 28 were evaluated for response.1 Of the
28 children and adolescents evaluated, 11 children were identified
to have tumours with NTRK, ROS1 or ALK fusions and one with ALK
F1174L-mutated neuroblastoma (NBL).1 A summary of
the results are included below.
-
Complete responses were observed in 2 patients
with tumours harbouring NTRK and ALK fusions: 1 with an NTRK
fusion-positive primary CNS tumour and 1 with an ALK
fusion-positive inflammatory myofibroblastic tumour. Another
complete response was observed in 1 neuroblastoma patient with an
ALK F1174L mutation.1
-
Partial responses were observed in 9 patients, 3
unconfirmed at the time of the clinical cut-off date, across NTRK,
ROS1 and ALK fusion-positive primary CNS (n=4) and extracranial
(n=5) solid tumours.1
-
Median duration of therapy for confirmed
fusion-positive responders was 10.51 months (3.8 to 17.7 months),
and median time to response was 1.89 months (1 to 1.9
months).1
-
The safety profile of entrectinib was consistent
with that seen in previous analyses. Treatment-related adverse
events were most frequently National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events Grade 1 or 2, leading to
discontinuation in 6.9% of patients.1
About NTRK fusion-positive cancer
Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer
occurs when the NTRK1/2/3 genes fuse with other genes, resulting in
altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling
pathways involved in proliferation of certain types of cancer. NTRK
gene fusions are tumour-agnostic, meaning they are present in
tumours irrespective of site of origin. These fusions have been
identified in a broad range of solid tumour types, including
breast, cholangiocarcinoma, colorectal, gynaecological,
neuroendocrine, non-small cell lung, salivary gland, pancreatic,
sarcoma and thyroid cancers.3
About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in
development for the treatment of locally advanced or metastatic
solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a
selective tyrosine kinase inhibitor designed to inhibit the kinase
activity of the TRK A/B/C and ROS1 proteins, whose activating
fusions drive proliferation in certain types of cancer.4,5 Entrectinib
can block ROS1 and NTRK kinase activity and may result in the death
of cancer cells with ROS1 or NTRK gene fusions.[4,5] Entrectinib is
being investigated across a range of solid tumour types, including
breast, cholangiocarcinoma, colorectal, gynaecological,
neuroendocrine, non-small cell lung, salivary gland, pancreatic,
sarcoma and thyroid cancers.2,3
Entrectinib has been granted Breakthrough Therapy Designation (BTD)
by the FDA; Priority Medicines (PRIME) designation by the European
Medicines Agency (EMA); and Sakigake designation by the Japanese
health authorities for the treatment of NTRK fusion-positive,
locally advanced or metastatic solid tumours in adult and
paediatric patients who have either progressed following prior
therapies or have no acceptable standard therapies.2
About Roche
Roche is a
global pioneer in pharmaceuticals and diagnostics focused on
advancing science to improve people's lives. The combined strengths
of pharmaceuticals and diagnostics under one roof have made Roche
the leader in personalised healthcare - a strategy that aims to fit
the right treatment to each patient in the best way
possible.
Roche is the world's largest biotech company, with truly
differentiated medicines in oncology, immunology, infectious
diseases, ophthalmology and diseases of the central nervous system.
Roche is also the world leader in in vitro diagnostics and
tissue-based cancer diagnostics, and a frontrunner in diabetes
management.
Founded in 1896, Roche continues to search for better ways to
prevent, diagnose and treat diseases and make a sustainable
contribution to society. The company also aims to
improve patient access to medical innovations by working with
all relevant stakeholders. Thirty medicines developed by Roche are
included in the World Health Organization Model Lists of Essential
Medicines, among them life-saving antibiotics, antimalarials and
cancer medicines. Moreover, for the tenth consecutive year, Roche
has been recognised as the most sustainable company in the
Pharmaceuticals Industry by the Dow Jones Sustainability Indices
(DJSI).
The Roche Group, headquartered in Basel, Switzerland, is active in
over 100 countries and in 2017 employed about 94,000 people
worldwide. In 2017, Roche invested CHF 10.4 billion in R&D and
posted sales of CHF 53.3 billion. Genentech, in the United States,
is a wholly owned member of the Roche Group. Roche is the majority
shareholder in Chugai Pharmaceutical, Japan. For more information,
please visit www.roche.com.
All trademarks used or mentioned in this release are protected by
law.
References
[1] Robinson G,
et al. Phase 1/1B trial to assess the activity of entrectinib in
children and adolescents with recurrent or refractory solid tumors
including central nervous system (CNS) tumors. American Society of
Clinical Oncology; May 31-Jun 4, 2019; Chicago, USA. Abstract
10009.
[2] F. Hoffman La Roche Ltd. Data on file.
[3] Demetri GD, et al. Efficacy and Safety of Entrectinib in
Patients with NTRK Fusion-Positive (NTRK-fp) Tumors: Pooled
Analysis of STARTRK-2, STARTRK-1 and ALKA-372-001. Presented at
ESMO 2018; October 19-23, 2018; Munich, Germany. Abstract
LBA17.
[4] Ahn M-J, Cho BC, Siena S, et al. Entrectinib in patients with
locally advanced or metastatic ROS1 fusion-positive non-small cell
lung cancer (NSCLC). Presented at: IASLC 18th World Conference on
Lung Cancer; October 15-18, 2017; Yokohama, Japan. Abstract
8564.
[5] Rolfo, et al. Entrectinib: a potent new TRK, ROS1, and ALK
inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500.
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