A phase I study of MM-302, an antibody-drug conjugated human epidermal growth factor receptor 2 (HER2)-targeted liposomal doxorubicin, as a monotherapy or in combination with trastuzumab or trastuzumab and cyclophosphamide had a manageable safety profile and encouraging efficacy results in a group of heavily pretreated women with HER2-positive metastatic breast cancer.
The results of the study were presented by Patricia LoRusso, DO, professor of medicine in the division of oncology at Yale University in New Haven, Connecticut, at the American Association for Cancer Research (AACR) Annual Meeting.
Patients in the study who received at least 30 mg/m2 of MM-302 plus trastuzumab had a median progression-free survival of 7.6 months (95% confidence interval [CI], 3.6–10.9); those treated with the addition of cyclophosphamide had a median progression-free survival of 10.6 months (95% CI, 1.8–10.6).
“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,” said LoRusso in a prepared statement.
The trial included 69 patients with HER2-positive metastatic breast cancer who had a median of four prior treatment regimens for their disease. They were assigned to one of four treatment arms:
1) MM-302 alone at 8, 16, 30, 40, and 50 mg/m2 every 4 weeks,
2) MM-302 at 30 and 40 mg/m2 every 4 weeks plus trastuzumab at 4 mg/kg every 2 weeks,
3) MM-302 at 30 mg/m2 every 3 weeks plus trastuzumab at 6 mg/kg every 3 weeks, or
4) MM-302 at 30 mg/m2 every 3 weeks plus trastuzumab at 6 mg/kg every 3 weeks and cyclophosphamide at 450 mg/m2 every 3 weeks.
Twelve percent of patients responded to treatment with at least 30 mg/m2 of MM-302 alone or in combination with trastuzumab.
Only one patient had a dose-limiting toxicity of febrile neutropenia and the maximum tolerated dose was not reached. MM-302 at a 30 mg/m2 every 3 weeks dosage in combination with trastuzumab is under investigation in a phase II trial.
The most common grade 3/4 adverse event was neutropenia, which occurred in eight patients. Adverse events occurring in more than 20% of patients included constipation, cough, decreased appetite, diarrhea, dyspnea, fatigue, nausea, neutropenia, stomatitis, and vomiting.
Looking at cardiac effects, the researchers found that left ventricular ejection fraction reductions below 50% or a greater than 10 percentage point drop from baseline occurred in six patients (9%). One patient had grade 1 cardiac failure resulting in treatment discontinuation.