974PD - A Phase 1 Study of the Anti-Erbb3 Antibody Mm-121 in Combination with Weekly Paclitaxel in Patients with Advanced Gynecological and Breast Cancers

Abstract

ABSTRACT Background MM-121 is a fully human monoclonal antibody targeting the epidermal growth factor receptor family member ErbB3. ErbB3 has been widely implicated in driving cancer growth and in the development of resistance to conventional chemotherapies and targeted agents across multiple malignancies. Single agent weekly paclitaxel is a standard regimen for patients with advanced gynecological and metastatic breast cancers. Here we present results from an ongoing Phase 1 study evaluating the combination of MM-121 and weekly paclitaxel. Methods A total of 24 patients with either platinum resistant ovarian cancer, metastatic endometrial cancer, or HER2 negative metastatic breast cancer, were treated in a dose escalation (12 pts) or expansion cohort (12 pts). Patients were treated until disease progression or intolerable toxicity. Response was assessed every eight (8) weeks according to RECIST 1.1. In the dose-expansion cohorts, pre- and post-treatment fresh tumor biopsies were obtained from 12 patients to assess ErbB3 signaling status and its potential as a predictive marker for MM-121 response. Results To date, 24 patients have been treated with a median follow up of 5.5 months (range 0.8 – 13.1). The median age was 58 years (range 38 – 72), and patients had received a median of four (range 1 – 11) prior lines of therapy. Common (>20%) adverse events of any grade included fatigue (62%), peripheral neuropathy (58%), diarrhea (46%), neutropenia (46%) and rash (38%). Grade 3/4 toxicities included fatigue (17%), peripheral neuropathy (8%), diarrhea (12%), neutropenia (16%), anemia (4%), abdominal pain (8%), and hypokalemia (4%). 17 (71%) patients were evaluable for response and the overall clinical benefit rate, defined as PR or SD lasting for >4 months, was 71%. 47% achieved a PR and 35% a confirmed PR with a median duration of response of 4.6 months (range1.7 – 9.6) and 24% had SD >4 months with a median duration of SD of 5.6 months (range 4.2-12.6). 17% patients had PD at first assessment and 38% remain on study with a median on-study time of 10.2 months (range 1.4 – 13.1). Translational analyses exploiting tissue analysis in combination with in silico modeling are ongoing. Conclusion The combination of MM121 and paclitaxel showed activity in metastatic ovarian and breast cancers. Disclosure J. Liu: Joyce Liu is an investigator participating in the corporate-sponsored study which is the subject of the abstract. R. Patel: Ravi Patel is an investigator participating in the corporate-sponsored study which is the subject of the abstract. G. Kato: Giraldo Kato is an investigator participating in the corporate-sponsored study which is the subject of the abstract. U. Matulonis: Ursula Matulonis is an investigator participating in the corporate-sponsored study which is the subject of the abstract. V. Moyo: Victor Moyo is employed by and owns stock in the corporate sponsor of this reserach. K. Riahi: Kaveh Riahi is employed by and owns stock in the corporate sponsor of this research. J. Pearlberg: Joseph Pearlberg is employed by and owns stock in a corporate sponsor of this research. A. Czibere: Akos Czibere is employed by and owns stock in the corporate sponsor of this research. S. Isakoff: Steven Isakoff is an investigator participating in the corporate-sponsored study which is the subject of the abstract. He has also served as a consulant to Merrimack Pharmaceuticals.