Oncothyreon Inc. (Nasdaq:ONTY), a clinical-stage biopharmaceutical
company dedicated to the development of therapeutic products that
can improve the lives and outcomes of patients with cancer, today
announced updated data from the company’s ongoing trials of
ONT-380, an orally active, reversible and selective small-molecule
HER2 inhibitor being developed for the treatment of HER2-positive
metastatic breast cancer. The data will be the subject of two
presentations at the San Antonio Breast Cancer Symposium (SABCS)
being held December 8-12, 2015 in San Antonio, TX.
The first presentation (Abstract P4-14-20) highlights data from
a Phase 1b trial of ONT-380 in combination with Kadcyla®
(ado-trastuzumab emtansine or T-DM1) in patients who have
previously failed treatment with Herceptin® (trastuzumab) and a
taxane for HER2-positive breast cancer (ClinicalTrials.gov
Identifier NCT01983501). The data demonstrate an overall
response rate of 41% and a clinical benefit rate (CBR) of 59% in an
advanced stage patient population, 60% of whom have a history of
central nervous system (CNS) metastases. The CNS CBR for patients
with response assessable CNS metastases was 64%. The second
presentation (Abstract P4-14-19) combines data for patients with
response assessable brain metastases from two trials, the Phase 1b
trial in combination with Kadcyla and a Phase 1b trial of ONT-380
in combination with Herceptin and/or Xeloda® (capecitabine)
(ClinicalTrials.gov Identifier NCT02025192). The analysis
includes patients with previously untreated CNS metastases as well
as patients with progressive or new CNS metastases after prior
treatment with radiation or surgery. Responses and clinical
benefit in the CNS were seen for both groups and in all
combinations tested.
“We are pleased by the response rate and clinical benefit rate
we have seen in the combination trial of ONT-380 and Kadcyla,
including in patients with brain metastases,” said Robert L.
Kirkman, M.D., President and CEO of Oncothyreon. “In addition, the
analysis of patients with response assessable brain metastases from
both our trials reinforce and expand upon our previously reported
results, increasing our commitment to exploring ONT-380 in this
indication. Our planned Phase 2 trial of ONT-380 in
combination with Xeloda and Herceptin includes significant
CNS-focused endpoints. We also plan to explore additional
options to develop ONT-380 in combination with Kadcyla in patients
with CNS metastases.”
“CNS metastases occur in up to 50 percent of women with
HER2-positive metastatic breast cancer, and these patients have
limited options for systemic treatment,” said Stacy Moulder, M.D.,
Associate Professor, Section Chief of Clinical Research, Breast
Medical Oncology, University of Texas MD Anderson Cancer Center.
“The level of clinical activity seen in the expanded data set for
ONT-380 in these advanced stage patients is encouraging and worthy
of urgent further development.”
About the Clinical Results
The Phase 1b trial of ONT-380 in combination with Kadcyla is a
dose escalation trial in patients with HER2-positive metastatic
breast cancer who have been previously treated with Herceptin and a
taxane. Patients with a history of CNS metastases, including
patients with untreated asymptomatic metastases and patients with
progression following prior local therapy, were eligible for
enrollment in the trial. The trial enrolled a total of 57
patients. The maximally-tolerated dose (MTD) of ONT-380 in
this trial was determined to be 300 mg given twice per day, and the
detailed safety and efficacy results included here are for 50
patients treated at this dose. For this patient population,
the median number of prior non-hormonal systemic treatments was two
(range 0-6). Twenty-three (46%) of the patients had received
prior Perjeta® (pertuzumab) therapy and 10 (20%) had received prior
Tykerb® (lapatinib) therapy. Thirty (60%) of the patients had
CNS metastases, of whom 19 had prior therapy for those
metastases.
Best responses were measured using RECIST 1.1 criteria in 48
evaluable patients. In 34 patients with measurable disease, a
best response of a confirmed partial response (cPR) was seen in 14
(41%), stable disease (SD) in 15 (44%) and progressive disease (PD)
in 5 (15%). Fourteen patients had non-target lesions,
primarily bone metastases, none of whom had a best response of PD
(all were non-CR/non-PD by RECIST 1.1). The CBR, defined as
patients with a complete response (CR), a cPR, or either SD or
non-CR/non-PD for at least 6 months, was 59% (23/39).
Patients active on study at the time of the analysis with SD for
less than six months were excluded from the calculation of
CBR. Twenty patients had response assessable CNS
metastases. Of these patients twelve had measurable lesions
and a follow-up scan, with a best CNS response of one CR, three PRs
and eight SDs, for an overall response rate of 33%. One patient did
not have a follow-up CNS scan as a result of progressive systemic
disease. All seven patients with assessable non-target lesions had
non-CR/non-PD as a best response. The CNS CBR was 64%.
A calculation of progression free survival is not yet possible in
this trial, as 25 of the 50 patients enrolled at the MTD remained
active on the study at the time of the analysis.
Combination therapy with ONT-380 and Kadcyla was well-tolerated
in this trial. The most common clinical adverse events were
nausea, vomiting, diarrhea, vomiting and constipation, the majority
of which were Grade 1 in severity. The most common laboratory
abnormality was elevation in liver function tests (ALT/AST), the
majority of which were Grade 1 or 2. All elevations in
ALT/AST which were Grade 3 or greater were reversible with dose
interruption, except in the setting of progressive metastatic liver
disease, and most patients with Grade 3 or greater elevations were
able to resume treatment with reduced dose ONT-380 and/or
Kadcyla.
The role of ONT-380 in the treatment of CNS metastases from
HER2-positive breast cancer was further evaluated in a combined
analysis of 34 patients with response-assessable CNS metastases
from both the Phase 1b trial of ONT-380 in combination with Kadcyla
and the Phase 1b trial of ONT-380 in combination with Herceptin
and/or Xeloda. CNS metastases were considered response
assessable if they were either untreated with radiation or surgery,
or were new or progressive lesions following prior radiation or
surgery. Of 14 patients with previously untreated lesions,
eight had measurable disease, with a best CNS response of one CR,
two cPRs and four SDs. One patient did not have a follow up
CNS scan secondary to progressive systemic disease. Six
patients with previously untreated lesions had non-target lesions
only, of whom five were non-CR/non-PD and one was not
evaluable. The CNS CBR for the previously untreated CNS
metastases was 44%. Of 20 patients with new or progressive
lesions following prior therapy, 17 had measurable disease, with a
best CNS response of five cPRs, nine SDs, and one PD. Two
patients remain too early to evaluate. Three patients with
non-target lesions only had non-CR/non-PD. The CNS CBR for
patients with new or progressive lesions following prior therapy
was 59%. Of note, responses and clinical benefit were seen
when ONT-380 was combined with each of Kadcyla, or Herceptin and/or
Xeloda.
About the Planned ONT-380 Clinical Development
Program
Oncothyreon plans to initiate a Phase 2 randomized,
double-blind, controlled study of ONT-380 versus placebo in
combination with capecitabine and trastuzumab in patients with
unresectable locally advanced or metastatic HER2-positive breast
cancer (ClinicalTrials.gov Identifier: NCT02614794). The
trial is expected to enroll approximately 180 patients in multiple
centers located in the United States, Canada and Western
Europe. Eligible patients must have centrally confirmed
HER2-positive breast cancer and must have been previously treated
with a taxane, trastuzumab, pertuzumab and TDM-1. The primary
endpoint of the trial is bi-compartmental progression free
survival, both CNS and non-CNS, as assessed by independent review
using both RECIST 1.1 and Response Assessment in Neuro-Oncology -
Brain Metastases (RANO-BM) criteria. Secondary endpoints
include time to CNS progression, objective response rate, CBR rates
for both CNS and non-CNS metastatic disease and overall
survival. Oncothyreon currently expects to initiate the first
clinical sites for the Phase 2 trial before the end of 2015 and to
treat the first patient in early 2016.
Based on the results of the Phase 1b trial of ONT-380 in
combination with Kadcyla discussed above, Oncothyreon is
considering an additional Phase 2 or Phase 3 trial of this
combination potentially focused on patients with CNS
metastases. Oncothyreon plans to discuss potential designs
for this trial, together with the overall registration strategy for
ONT-380, with regulatory authorities, including the United States
Food and Drug Administration, in the first part of 2016.
Conference Call Information
To participate in the call being held at 4:30 p.m. Eastern Time
(1:30 p.m. Pacific) to discuss new clinical data from ongoing
clinical trials of ONT-380, please dial (877) 280-7291 (United
States) or (707) 287-9361 (International). In addition, the
call will be webcast live and can be accessed on the "Events" page
of the "News & Events" section of Oncothyreon’s website at
www.oncothyreon.com. An archive of the webcast will be available
after completion of the discussion and will be posted on the
Oncothyreon website.
About Oncothyreon
Oncothyreon is a clinical-stage biopharmaceutical company
specializing in the development of innovative therapeutic products
for the treatment of cancer. Our goal is to discover, develop and
commercialize novel compounds that have the potential to improve
the lives and outcomes of cancer patients. Our most advanced
product candidate is ONT-380, an orally active and selective small
molecule HER2 inhibitor. We are developing preclinical product
candidates in oncology and immune-oncology using our protocell
technology. For more information, visit www.oncothyreon.com.
Forward-Looking Statements
In order to provide Oncothyreon's investors with an
understanding of its current results and future prospects, this
release contains statements that are forward-looking. Any
statements contained in this press release that are not statements
of historical fact may be deemed to be forward-looking statements.
Words such as "believes," "anticipates," "plans," "expects,"
"will," "intends," "potential," "possible" and similar expressions
are intended to identify forward-looking statements. These
forward-looking statements include Oncothyreon's expectations
regarding clinical development activities.
Forward-looking statements involve risks and uncertainties
related to Oncothyreon's business and the general economic
environment, many of which are beyond its control. These risks,
uncertainties and other factors could cause Oncothyreon's actual
results to differ materially from those projected in
forward-looking statements, including those predicting the timing,
duration and results of clinical trials, the timing and results of
regulatory reviews, the safety and efficacy of our product
candidates, and the indications for which our product candidates
might be developed. There can be no guarantee that the results of
preclinical studies or clinical trials will be predictive of either
safety or efficacy in future clinical trials. Although Oncothyreon
believes that the forward-looking statements contained herein are
reasonable, it can give no assurance that its expectations are
correct. All forward-looking statements are expressly qualified in
their entirety by this cautionary statement. For a detailed
description of Oncothyreon's risks and uncertainties, you are
encouraged to review the documents filed with the securities
regulators in the United States on EDGAR and in Canada on SEDAR.
Oncothyreon does not undertake any obligation to publicly update
its forward-looking statements based on events or circumstances
after the date hereof.
CONTACT:
Investor Relations:
Julie Rathbun
Rathbun Communications
206-769-9219
ir@oncothyreon.com
Media Relations:
Kelly France, Ph.D.
BrewLife
415-946-1076
kfrance@brewlife.com
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