– Phase I/II study of entrectinib, an investigational medicine,
showed responses in all pediatric tumor types harboring 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, May 15, and will
be presented at the 2019 ASCO Annual Meeting on Sunday, June 2 –
SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (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 tumors with and without
neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic
lymphoma kinase (ALK) gene fusions. The study showed entrectinib shrank
tumors (objective response rate; ORR) in all children and adolescents
who had NTRK, ROS1 or ALK fusion-positive solid tumors (11 of 11
patients), including two patients achieving a complete response. Of the
11 patients, five patients with primary high-grade tumors in the central
nervous system (CNS) had an objective response, including one patient
with a complete response. The safety profile of entrectinib was
consistent with that seen in previous analyses. Data will be presented
at the American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago on Sunday, June 2, 2019, from 8:00 – 8:12 a.m. CDT (Abstract
10009), and was part of today’s official ASCO presscast.
“We are encouraged by the results we have seen with entrectinib in
children with pediatric and adolescent cancers, including those with
tumors in the brain,” said Sandra Horning, M.D., 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 personalized medicines developed specifically for their type of
cancer.”
Additional data for entrectinib across different tumor types and patient
populations will also be presented at ASCO, highlighting the company’s
unique approach to personalized 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 tumors and CNS metastases
will be presented on Saturday, June 1, 2019, in a poster session from
3:00 – 4:30 p.m. 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, June 2, 2019, from 8:00 – 11:00 a.m. CDT (Abstract 9070).
The FDA recently granted Priority Review for entrectinib for both the
treatment of pediatric and adult patients with NTRK fusion-positive,
locally advanced or metastatic solid tumors 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. 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 August 18, 2019.
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 tumors or primary CNS tumors,
with or without NTRK, ROS1 or ALK fusions. 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 tumors, Response Evaluation
Criteria in Solid Tumors (RECIST), and Curie score (CS) for
neuroblastoma. The study enrolled 29 children and adolescents aged 4.9
months through 20 years (median age of 7 years) who had recurrent or
refractory solid tumors, and 28 were evaluated for response. Of the 28
children and adolescents evaluated, 11 children were identified to have
tumors with NTRK, ROS1 or ALK fusions and one with ALK F1174L-mutated
neuroblastoma. A summary of the results are included below.
-
Complete responses were observed in two patients with tumors harboring
NTRK and ALK fusions: one with an NTRK fusion-positive primary CNS
tumor and one with an ALK fusion-positive inflammatory myofibroblastic
tumor. Another complete response was observed in one neuroblastoma
patient with an ALK F1174L mutation. -
Partial responses were observed in nine patients, three 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 tumors. -
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). -
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 (CTCAE) Grade 1 or 2, leading to discontinuation in
6.9 percent of patients.
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 tumor-agnostic, meaning they are present in tumors
irrespective of site of origin. These fusions have been identified in a
broad range of solid tumor types, including breast, cholangiocarcinoma,
colorectal, gynecological, neuroendocrine, non-small cell lung, salivary
gland, pancreatic, sarcoma and thyroid cancers.
About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in
development for the treatment of locally advanced or metastatic solid
tumors that harbor 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. Entrectinib can block ROS1 and
NTRK kinase activity and may result in the death of cancer cells with
ROS1 or NTRK gene fusions. Entrectinib is being investigated across a
range of solid tumor types, including breast, cholangiocarcinoma,
colorectal, gynecological, neuroendocrine, non-small cell lung, salivary
gland, pancreatic, sarcoma and thyroid cancers.
About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology
company that discovers, develops, manufactures and commercializes
medicines to treat patients with serious and life-threatening medical
conditions. The company, a member of the Roche Group, has headquarters
in South San Francisco, California. For additional information about the
company, please visit http://www.gene.com.
Contacts
Media Contact:
Meghan Cox, (650) 467-6800
Advocacy Contact:
Stephanie Bryant, (312) 505-9789
Investor Contacts:
Loren Kalm, (650) 225-3217
Karl Mahler, 011
41 61 687 8503