On October 30, 2013 Merrimack reported results of a global, Phase 2, open-label, randomized study of MM-121 in combination with paclitaxel versus paclitaxel alone in patients with platinum-resistant or platinum-refractory advanced ovarian cancers (Press release Merrimack, OCT 30, 2013, View Source [SID:1234500597]).

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This study did not meet the primary endpoint of progression free survival in the overall population. The hazard ratio (HR) for progression free survival (PFS) was 1.0 [95% CI 0.74 – 1.4].

Ongoing analysis of a pre-specified set of biomarkers mechanistically linked to ErbB3 signaling identified a potential subpopulation of patients benefiting from MM-121 treatment in combination with paclitaxel. When using a combination of two biomarkers, the hazard ratio for PFS was 0.37 [95% CI 0.2 – 0.8] in the 34% of patients who were biomarker positive. The hazard ratio for PFS in the biomarker negative population was 1.54 [95% CI 1.0 – 2.4].

An overall increase in all grades of gastrointestinal toxicities, including diarrhea (73.6% vs. 42.5%), vomiting (31.4% vs. 18.8%) and other mucosal toxicities such as rhinitis (7.1% vs. 1.3%), epistaxis (23.6% vs. 17.5%), stomatitis (22.1% vs. 10.0%) and mucosal inflammation (22.1% vs. 1.3%), were observed in the combination as compared to paclitaxel alone, the majority of which were mild to moderate in severity. An increase in the pulmonary embolism rate was observed with the combination of MM-121 and paclitaxel (5.0% vs. 1.2%). No enhancement of paclitaxel-related peripheral neuropathy was reported with the combination.

"This unique study design lays the groundwork for future translational studies in ovarian cancer. The rapid enrollment into this study was a testament to the commitment of patients and physicians to advance our knowledge and improve upon available therapies in advanced ovarian cancers," said Dr. Akos Czibere, Clinical Director of the MM-121 program at Merrimack. "These data are a step forward for women with ovarian cancer."

"Research at Merrimack and elsewhere has shown that ligand-driven signaling through ErbB3 is one way in which cancer cells become resistant to therapy," said Gavin MacBeath, Ph.D., Co-Founder and Vice President of Translational Research at Merrimack. "MM-121 was designed to block this pathway. We are particularly encouraged by the biomarker findings in this trial, which are consistent with our preclinical hypotheses. This gives us increased confidence in our network biology platform and in our translational program at Merrimack."

This study was designed to evaluate whether MM-121 in combination with paclitaxel is more effective than paclitaxel alone, based on progression free survival. Patients were randomized at a 2:1 ratio for MM-121 in combination with paclitaxel versus paclitaxel alone. The study was conducted in the United Stated and Europe, and 223 patients were randomized. Patients enrolled in this study had locally advanced/metastatic or recurrent epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer, had received at least one prior platinum-based chemotherapy regimen, and were platinum-resistant or refractory. The full data from the study will be presented at a future conference.