Oncothyreon Inc. (Nasdaq:ONTY) today announced that positive
preliminary data from two ongoing Phase 1b trials of ONT-380
(ARRY-380), an orally active, reversible and selective small
molecule HER2 inhibitor, will be presented at the San Antonio
Breast Cancer Symposium.
The first trial (ClinicalTrials.gov Identifier NCT02025192) is a
parallel dose-escalation study of ONT-380 in combination with
Xeloda® (capecitabine) and/or Herceptin® (trastuzumab) in patients
previously treated with Herceptin and Kadcyla® (ado-trastuzumab
emtansine or TDM-1) for metastatic breast cancer. Interim data will
be presented for 21 patients, including seven in the ONT-380 plus
Xeloda cohort, eight in the ONT-380 plus Herceptin cohort, four in
the ONT-380 plus Xeloda and Herceptin cohort, and two in an ongoing
expansion cohort in patients with untreated or progressive central
nervous system (CNS) metastases, both treated with ONT-380 plus
Herceptin.
Seventeen of the patients were evaluable for best overall
response using RECIST 1.1 criteria. In the ONT-380 plus Xeloda
cohort, four patients had a partial response (PR) and three
patients had stable disease (SD), for an overall clinical benefit
rate of 100 percent (defined as either PR/CR or stable disease for
>6 months). In the ONT-380 plus Herceptin cohort, best response
has been a complete response (CR) in one patient, PR in two
patients, SD in four patients, and progressive disease (PD) in one
patient. Two patients in the ONT-380 plus Xeloda and Herceptin
cohort are currently evaluable, one of whom had a PR and one
PD. One patient in the CNS expansion cohort had a PR and the
other SD.
Fourteen of the 21 patients in this trial had a history of CNS
metastases, of whom six had evaluable target lesions per modified
RECIST 1.1 at the time of entry into the trial. Of these, best
initial response has been SD, with decreases in CNS target lesions
in four patients. Five of these six patients remain active on
study.
The second trial (ClinicalTrials.gov Identifier NCT01983501) is
a dose-escalation study of ONT-380 in combination with Kadcyla in
patients who have been previously treated with Herceptin and a
taxane for metastatic breast cancer. Data will be presented for 17
patients, of whom 16 were evaluable for response. Patients in this
trial were heavily pre-treated, having received a median of two
prior systemic treatments for metastatic disease, including prior
pertuzumab in six, and prior lapatinib in five. Best overall
response has been PR in five patients, SD in seven patients, and PD
in four patients. Nine patients in this trial had a history of
CNS metastases, of whom four had measurable disease per modified
RECIST 1.1 at the time of entry into the trial. Three of these
four patients have SD in the CNS and remain active on the study,
including two with decreases in measurable target lesions.
ONT-380 was well-tolerated in both studies and in all
combinations tested. The most common adverse events included
nausea and vomiting, diarrhea, fatigue and elevated liver function
tests. Most adverse events were grade 1 or 2 in severity.
Elevated liver function tests were more common in patients also
receiving Kadcyla. No grade 3 diarrhea was seen in either trial;
anti-diarrheal prophylaxis was not a study requirement.
A maximally tolerated dose (MTD) for ONT-380 has not been
identified to date in any of the combinations tested in either
trial. An improved tablet formulation of ONT-380 with
increased absorption was used in these trials compared to the
powder in capsule formulation used in the previously reported Phase
1 trial. All patients in both current trials received an
initial dose of 300 mg twice per day. At that dose, measured
drug levels were similar to those seen with 600 mg twice per day
(the single agent MTD) of the prior formulation. Drug exposure
in the current trials was well above the level needed for 90
percent inhibition of HER2.
"The preliminary signs of efficacy in both of these trials are
encouraging for the further development of ONT-380," said Stacy
Moulder, M.D., Associate Professor, Breast Medical Oncology,
University of Texas MD Anderson Cancer Center. "These patients were
heavily pre-treated, with the majority already having a history of
CNS metastases. Nevertheless, meaningful responses and
prolonged stable disease have been observed and many patients
currently remain on study. Importantly, ONT-380 has been
well-tolerated, with a toxicity profile that facilitates its
combination with other agents."
"We are continuing to enroll patients in both of these Phase 1b
trials," said Diana Hausman, M.D., Chief Medical Officer of
Oncothyreon. "We are currently testing an increased dose level
of ONT-380 of 350 mg twice daily in both trials. We are also
enrolling cohorts of patients in both trials with CNS metastases
from HER2+ breast cancer that are either asymptomatic and untreated
or progressive following treatment to better define the potential
role of ONT-380 in treating patients with this serious unmet
medical need."
About ONT-380
ONT-380 is an orally active, reversible and selective HER2
inhibitor invented at Array BioPharma Inc. In multiple preclinical
tumor models, ONT-380 was well tolerated and demonstrated
significant dose-related tumor growth inhibition that was superior
to Herceptin® (trastuzumab) and Tykerb® (lapatinib). Additionally,
in these models, ONT-380 demonstrated synergistic or additive tumor
growth inhibition when dosed in combination with the
standard-of-care therapeutics Herceptin or Taxotere® (docetaxel).
ONT-380 has also demonstrated superior activity, based on overall
survival, compared to Tykerb® and to the investigational drug,
neratinib, in an intracranial HER2 positive breast cancer xenograft
model.
A Phase 1 trial of ONT-380, with both dose-escalation and
expansion components, has been completed in 50 patients, 43 of whom
had HER2 positive metastatic breast cancer. All HER2 positive
breast cancer patients had progressed on a Herceptin-containing
regimen. In addition, over 80 percent had been treated with Tykerb,
with many having progressed on therapy. In this study, ONT-380
demonstrated an acceptable safety profile; treatment-related
adverse events were primarily Grade 1. Because ONT-380 is selective
for HER2 and does not inhibit EGFR, there was a low incidence and
severity of treatment-related diarrhea, rash and fatigue.
Additionally, there were no treatment-related cardiac events or
Grade 4 treatment-related adverse events reported. Twenty-two HER2
positive breast cancer patients with measurable disease were
treated with ONT-380 at doses greater than or equal to 600 mg BID.
In this heavily pretreated patient population, there was a clinical
benefit rate (partial response [n = 3] plus stable disease for at
least 6 months [n = 3]) of 27 percent.
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 current
clinical-stage product candidates include ONT-380, an orally active
and selective small molecule HER2 inhibitor, and ONT-10, a
therapeutic vaccine targeting MUC1. We are developing preclinical
product candidates in oncology, and potentially certain rare
diseases, using our recently acquired 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.
Additional Information
Additional information relating to Oncothyreon can be found on
EDGAR at www.sec.gov and on SEDAR at www.sedar.com.
CONTACT: Investor and Media Relations Contact:
Julie Rathbun
Rathbun Communications
206-769-9219
ir@oncothyreon.com
Cascadian Therapeutics, Inc. (NASDAQ:CASC)
Historical Stock Chart
From Aug 2024 to Sep 2024
Cascadian Therapeutics, Inc. (NASDAQ:CASC)
Historical Stock Chart
From Sep 2023 to Sep 2024