In a related presentation at the AACR Annual Meeting,1 the antibody-drug conjugate DMUC5754A showed encouraging activity in women with ovarian cancer, particularly those with platinum-resistant disease, which currently lacks effective treatment options. The first-in-human phase I study included 44 patients with advanced, recurrent, platinum-resistant ovarian cancer. Of these difficult-to-treat patients, one achieved a complete response and four achieved partial responses.
Results of the phase I study were reported at a press conference by Joyce F. Liu, MD, MPH, Instructor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School in Boston.
Mechanism of Action
DMUC5754A consists of an antibody linked to a highly potent antimitotic toxin called MMAE. The antibody is targeted to the MUC16 protein expressed in ovarian cancers and releases the toxin with relative selectivity to the MUC16-positive cancer cells, which are expressed in 80% of patients with ovarian cancer. All five confirmed responses occurred in patients with high expression levels of MUC16 in their cancer cells, at the maximum tolerated dose of 2.4 mk/kg.
Dr. Liu explained that although chemotherapy and surgery are initially effective in the treatment of ovarian cancer, most patients will experience a recurrence, and platinum-resistant patients are challenging to treat, with limited therapeutic options.
The novel agent had tolerable safety, with fatigue as the most common grade 3 adverse event. Peripheral neuropathy was also reported but was manageable and reversible with dose adjustments.
“This is the first study of an antibody-drug conjugate in ovarian cancer. If the encouraging activity is confirmed in future studies, this would represent a real step forward in identifying new, effective treatments for a type of ovarian cancer that is difficult to treat,” Dr. Liu told listeners. Further trials evaluating DMUC5754A in advanced ovarian cancer are being planned. ■
Disclosure: Dr. Liu reported no potential conflicts of interest.
Reference
1. Liu J, Moore K, Birrer M, et al: Targeting MUC16 with the antibody-drug conjugate DMUC5754A in patients with platinum-resistant ovarian cancer: A phase I study of safety and pharmacokinetics. AACR Annual Meeting. Abstract LB-290. Presented April 9, 2013.
