BMN 673 for Breast Cancer and Ovarian Cancer

Chicago—The initial study in humans of the investigational agent BMN 673 found that the oral drug has substantial anti-tumor activity in deleterious germline BRCA ovarian and breast cancer, according to a phase 1/2 trial. The authors noted that BMN 673 was also well tolerated, and the recommended maximum tolerated dose should be 1 mg per day.

Results were presented during a poster session at the ASCO meeting. The poster was titled First-In-Human Trial of Novel Oral PARP Inhibitor BMN 673 In Patients with Solid Tumors.

This study had a 3 by 3 dose escalation design, in which patients took BMN 673 daily in 28-day cycles. The starting dose was 25 μg per day. Results from preclinical studies, as well as the drug’s clinical profile, suggested the once-daily administration would be best, according to the authors.

Patients were included in the study if they were at least 18 years of age and had an Eastern Cooperative Oncology Group performance status score of 0 or 1 and adequate organ function. They had escalation tumor types (n=39) or expansion tumor types (n=31).

Of the 70 patients enrolled, 60 were female. The median age was 58 years in the escalation tumor group and 45 years in the expansion tumor group. The majority of patients had ovarian or breast cancer. The authors presented results for 28 ovarian cancer patients and 18 breast cancer patients. Twelve of the breast cancer patients are still receiving treatment.

The authors said that no patients discontinued treatment due to an adverse event, although 11 patients had their dose reduced for myelosuppression. The most common serious adverse events were anemia, thrombocytopenia, and neutropenia, but all, except for one adverse event, were grade 3 or lower. Approximately 20% to 30% of patients had fatigue, nausea, or alopecia.

The germline BRCA ovarian cancer response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 44%, while the CA-125 response rate was 70% and the clinical benefit response rate was 82%. Of the 30 patients with ovarian cancer who responded to treatment, 27 were platinum sensitive, according to the authors.

For germline BRCA breast cancer, the response rate as measured by RECIST criteria was 39%, while the clinical benefit response rate was 67%. The authors noted that it was too early to evaluate a clinical benefit at 24 weeks of treatment for patients with breast cancer. They added that both patients who previously responded to platinum therapy responded to treatment with BMN 673. In addition, none of the 4 patients who did not respond to prior platinum therapy responded to BMN 673, and 5 of the 12 patients without any prior platinum exposure responded to BMN 673.

BioMarin Pharmaceutical Inc., the drug’s manufacturer, said in a news release that further data will be released at the European Society for Medical Oncology’s European Cancer Congress in September in Amsterdam, Netherlands. The study is currently enrolling patients with small-cell lung cancer as well as Ewing Sarcoma Family Tumors.

The company also announced it expects to begin enrolling patients with breast cancer for a study beginning in the fourth quarter of 2013.

BioMarin Pharmaceutical Inc. supported this study.