Merrimack Pharmaceuticals,
Inc. MACK announced updated and final clinical results for the Phase
1 study of MM-302, a novel HER2-targeted liposomal doxorubicin, in
HER2-positive metastatic breast cancer. The results were presented today by
Patricia LoRusso, D.O., in a clinical trials plenary oral session at the 2015
American Association for Cancer Research (AACR) Annual Meeting in
Philadelphia, PA. Data described the safety and promising clinical activity of
MM-302 in patients with advanced HER2-positive metastatic breast cancer.
Results from the trial showed that the group of patients (n=62) treated with
30 mg/m^2 or more of MM-302 alone, in combination with trastuzumab or with
trastuzumab and cyclophosphamide, had a median progression free survival
(mPFS) of 7.6 months (95% CI: 3.6-10.9 months) and an overall response rate
(ORR) of 11%. Of note, 25 patients who had not been previously treated with
anthracyclines had an mPFS of 11 months (95% CI: 1.8-13.1 months) and an ORR
of 24%.
"HER2-positive breast cancer affects approximately 20% of all breast cancer
patients and represents a particularly aggressive form of breast cancer.
Despite recent advancements in treatment, the vast majority of metastatic
breast cancer patients will progress and have a high need for additional
therapies," said Patricia LoRusso, D.O., professor of medicine in the Division
of Oncology at Yale University. "We are encouraged by these data on the safety
and promising clinical activity of MM-302 in patients who have exhausted many
therapeutic options for their disease. Our results support the further
evaluation of MM-302 in an anthracycline-naive population in the HERMIONE
trial."
The most frequent adverse events occurring in greater than 20% of the
population in this Phase 1 study were constipation, cough, decreased appetite,
diarrhea, dyspnea, fatigue, nausea, neutropenia, stomatitis and vomiting. The
most common Grade 3/4 adverse event was neutropenia observed in 8 patients.
Six out of 69 patients (9%) had protocol-defined asymptomatic declines in left
ventricular ejection fraction (LVEF). In 1 of the 6 patients, this was
reported as a Grade 1 cardiac failure that was possibly related to study
treatment.
"As an antibody-drug conjugate, MM-302 is designed to maximize targeted
delivery to the tumor while trying to reduce the cardiotoxic effects of
traditional anthracycline chemotherapies," said Thomas Wickham, Ph.D., Vice
President of Development and MM-302 Project Team Leader. "The study population
in this Phase 1 trial is heavily pre-treated, as the majority of patients have
already progressed on a median of four prior therapies. We are encouraged by
the 7.6 month median progression-free survival in this patient population and
are looking forward to our next steps for the MM-302 clinical development
program."
Merrimack is currently enrolling the HERMIONE study that is designed to
support a potential application for accelerated approval in the U.S. and
conditional marketing authorization in the E.U. The HERMIONE study is for
HER2-positive, metastatic breast cancer patients who are anthracycline-naive
and have not been previously treated with pertuzumab and T-DM1-containing
regimens.
METHODOLOGY AND RESULTS
A Phase 1 study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in
patients with HER2-positive metastatic breast cancer (mBC) Safety of MM-302
Data were presented on 69 patients treated in this Phase 1 trial. Patients
received a median of 4 prior therapies for metastatic disease.
Safety of MM-302
o Neutropenia was the most common Grade 3/4 adverse event occurring in 8
patients with 1 patient experiencing febrile neutropenia. The most
frequent all-grade adverse events occurring in >20% of the population were
constipation, cough, decreased appetite, diarrhea, dyspnea, fatigue,
nausea, neutropenia, stomatitis and vomiting.
o Protocol defined asymptomatic declines in left ventricle ejection fraction
(LVEF) were observed in six patients; four of these patients had
reversible declines consistent with trastuzumab-induced changes. One
patient experienced two reversible asymptomatic LVEF declines (classified
as a Grade 1 cardiac failure) that resulted in treatment discontinuation
after receiving 11 cycles of MM-302 in combination with trastuzumab.
o Patients treated with MM-302 as a monotherapy showed no signs of
protocol-defined decline in cardiac function.
o 11 of 69 patients received greater than 550 mg/m^2 of cumulative
doxorubicin dose.
Activity Data
o Seven of the 62 patients treated with 30 mg/m^2 or more MM-302 alone, in
combination with trastuzumab or with trastuzumab and cyclophosphamide had
a clinical response to treatment resulting in an overall response rate
(ORR) of 11%.
o Overall, the median progression-free survival (mPFS) in patients treated
with 30 mg/m^2 or more of MM-302 was 7.6 months (95% CI: 3.6-10.9 months).
o An ORR of 24% and an 11 month mPFS (95% CI: 1.8-13.1 months) was observed
in anthracycline-naive patients (n=25).
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