Merrimack Pharmaceuticals, MACK today announced Phase 1 clinical trial results for MM-302,
a novel HER2-targeted liposomal doxorubicin for the treatment of advanced
HER2-positive breast cancer. Primary objectives for the trial are to assess
the safety of MM-302 as a monotherapy and in combination with trastuzumab, as
well as to determine the Phase 2 dose for MM-302. Data were presented at the
2013 San Antonio Breast Cancer Symposium, Dec. 10-14, 2013 in San Antonio,
Texas.
Anthracyclines, particularly doxorubicin, have been an effective component of
breast cancer treatment for decades, though their use is ultimately limited by
cardiac toxicity. These cardiotoxic effects limit the use of traditional
anthracyclines in combination with targeted therapies, such as trastuzumab,
for treatment of HER2-positive breast cancer. MM-302 is specifically designed
to address this issue by delivering doxorubicin to tumor cells overexpressing
HER2, while minimizing uptake into normal cells, including those of the heart.
In this ongoing Phase 1 study, patients treated with MM-302 showed no signs of
clinical decline in cardiac function. The most common adverse events were
fatigue, nausea and decreased appetite; the rates of these events were
consistent across MM-302 as a monotherapy and in combination with trastuzumab.
Results from the trial also showed that patients treated with MM-302 as a
monotherapy at doses of 30, 40 and 50 mg/m^2 had an estimated progression free
survival (PFS) of 5.6 months (95% CI: 2.8-10.9 months) and a clinical benefit
response rate of 37%. Of note, 5 of 9 patients who had not been previously
treated with anthracyclines had a PFS of greater than 9 months.
"We are pleased with the data for this trial and the preliminary safety
profile for MM-302, particularly in regards to cardiac toxicity," said Ulrik
Nielsen, Chief Scientific Officer at Merrimack. "These results are encouraging
for the development of our nanoliposomal technology platform, and an important
step towards successfully establishing the safety and activity profile of
MM-302 in the HER2-positive breast cancer population."
A Phase 2 study for MM-302 is being planned in patients with HER2-positive
breast cancer.
METHODOLOGY AND RESULTS
Assessment of Safety and Activity in an Expanded Phase 1 Study of MM-302, a
HER2-targeted Liposomal Doxorubicin, in Patients with Advanced HER2-positive
(HER2+) Breast Cancer (Abstract #P4-12-29)
Safety of MM-302
* To evaluate the safety and tolerability of MM-302 both as a monotherapy
and in combination with trastuzumab, 47 patients with histologically
confirmed HER2-positive metastatic breast cancer were included in the
analysis. Patients received a median of 4 prior therapies for metastatic
disease.
* The study first used a standard 3 + 3 dose escalation design for the
monotherapy to determine a potential Phase 2 dose of MM-302. Patients were
enrolled across 5 dose levels ranging from 8 mg/m^2 to 50 mg/m^2 given
every 4 weeks. Expansion cohorts were performed at 40 and 50 mg/m^2 for a
total of 12 patients at each dose. Additional patients were then enrolled
in arms receiving MM-302 plus trastuzumab.
* Overall, MM-302 was well tolerated. As a monotherapy, the most frequent
all-grade adverse events were fatigue (65%), nausea (59%) and decreased
appetite (41%). The addition of trastuzumab did not appear to increase the
incidence of adverse events observed with the monotherapy alone.
* Neutropenia was the most common Grade 3/4 adverse event occurring in 7
patients (6 in the monotherapy arms and 1 in the combination arm). One
dose limiting toxicity was observed (febrile neutropenia) and the dose was
subsequently withheld; the patient went on to continue study treatment for
3 additional cycles.
* No clinically significant declines in left ventricle ejection fraction
(LVEF) were observed in patients treated with MM-302 or MM-302 plus
trastuzumab, including 8 patients who had been treated with lifetime
cumulative doxorubicin in excess of 500 mg/m^2.
Activity data
* Data was presented on 47 patients treated in the ongoing Phase 1 trial. Of
the 27 evaluable patients who were treated with 30, 40 and 50 mg/m^2 of
MM-302 as a monotherapy, 1 patient achieved a complete response (CR), 3
patients achieved a partial response (PR), and 6 patients experienced
stable disease (SD), resulting in a clinical benefit rate of 37%.
Estimated progression free survival (PFS) was 5.6 months (95% CI: 2.8-10.9
months).
* In anthracycline-naïve patients treated with MM-302 as a monotherapy, 4 of
the 9 patients achieved a CR or PR and 5 of the 9 patients had a PFS of 9
months or more.
* Of the 13 evaluable patients who were treated with MM-302 and trastuzumab,
4 were anthracycline-naïve. Of the 4 anthracycline-naïve patients, 2
achieved a PR and 1 experienced SD.
Imaging
* Tumor deposition and biodistribution of MM-302 was assessed in a subset of
patients using ^64Cu-labeled MM-302 and positron emission tomography
(PET)/computed tomography (CT).
* Accumulation of ^64Cu-labeled MM-302 was observed in metastatic lesions,
including in the brain and bone.
About Merrimack
Merrimack is a biopharmaceutical company discovering, developing and preparing
to commercialize innovative medicines paired with companion diagnostics for
the treatment of cancer. Merrimack applies its systems biology-based approach
to biomedical research throughout the research and development process.
Merrimack currently has six targeted therapeutic oncology therapeutics in
clinical development. For more information, please visit Merrimack's website
at www.merrimackpharma.com.
Forward-Looking Statement
To the extent that statements contained in this press release are not
descriptions of historical facts, they are forward-looking statements
reflecting the current beliefs and expectations of management made pursuant to
the safe harbor provisions of the Private Securities Litigation Reform Act of
1995, as amended. Forward-looking statements include any statements about
Merrimack's strategy, future operations, future financial position and future
expectations and plans and prospects for Merrimack, and any other statements
containing the words "anticipate," "believe," "estimate," "expect," "intend,"
"may," "plan," "predict," "project," "target," "potential," "will," "would,"
"could," "should," "continue," and similar expressions. In this press release,
Merrimack's forward-looking statements include statements about the potential
effectiveness and tolerability of MM-302 as a monotherapy and in combination
with trastuzumab in certain patient populations or subpopulations, its ability
to develop a predictive diagnostic or imaging agent and its ability to
translate clinical data into future clinical success. Such forward-looking
statements involve substantial risks and uncertainties that could cause
Merrimack's clinical development programs, future results, performance or
achievements to differ significantly from those expressed or implied by the
forward-looking statements. Such risks and uncertainties include, among
others, the uncertainties inherent in the initiation of future clinical
trials, availability of data from ongoing clinical trials, expectations for
regulatory approvals and other matters that could affect the availability or
commercial potential of Merrimack's drug candidates or companion diagnostics.
Merrimack undertakes no obligation to update or revise any forward-looking
statements. Forward-looking statements should not be relied upon as
representing Merrimack's views as of any date subsequent to the date hereof.
For a further description of the risks and uncertainties that could cause
actual results to differ from those expressed in these forward-looking
statements, as well as risks relating to Merrimack's business in general, see
the "Risk Factors" section of Merrimack's Quarterly Report on Form 10-Q filed
with the Securities and Exchange Commission (SEC) on November 8, 2013 and
other reports Merrimack files with the SEC.
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