CA125 becomes a Target for Destruction of Ovarian Cancer by Phase I Drug
The Clearity Foundation
Dr. Cory Bentley, PhD
Most ovarian cancer patients have become familiar with CA125 blood level monitoring, but trial drug DMUC5754A from Genentech puts a new twist on this familiar blood marker of advanced ovarian cancer. CA125 (cancer antigen 125) also goes by the name mucin 16, Muc16 for short. Muc16 is overexpressed on the cell surface of most ovarian cancers compared to normal tissue. So while Muc16 in the blood may be a biomarker for ovarian cancer, on the tumor cell surface it targets the cell for destruction by DMUC5754A.
DMUC5754A is a so-called therapeutic antibody that specifically binds to Muc16. It is much like the antibodies that one’s body naturally makes to fight off infection and invaders. DMUC5754A is also an armed antibody by its linkage to a highly toxic drug, MMAE (monomethyl auristatin E). An armed antibody is known as an ADC – antibody drug conjugate.
Phase I clinical trial data for ADC DMUC5754A were presented at this year’s American Association for Cancer Research (AACR) Annual Meeting in April. This phase I study evaluated several aspects of this drug in advanced recurrent platinum-resistant ovarian cancer, including safety and activity. This phase 1 trial had two parts; first, dose escalation to determine the maximum tolerated dose (MTD) and then expansion for further analysis at the MTD. Dose escalation design starts patients on a very low dose of the drug. These patients are closely monitored for side effects. If side effects are mild, the next group of patients receives a higher dose of the drug. Dose escalation continues in successive groups of patients until strong side effects are observed in greater than 30% of patients, establishing the MTD for DMUC5754A. The expansion part of the trial involved 22 more patients at this highest dose to test for potential efficacy and confirm the safety.
Of the 29 patients treated at the MTD, one complete response was observed (no evidence of cancer after treatment) and 4 partial responses were observed (decreased tumor size). All responses were seen in patients whose tumors expressed moderate to high levels of the targeted protein Muc16, suggesting that using Muc-16 expression on tumor cells will help to identify responsive patients in the future. Dr. Joyce Liu, who presented the phase I study, concluded that DMUC5754A “has an encouraging safety profile and evidence of anti-tumor activity in MUC16-expressing ovarian cancer.”
Finding responders in this group of patients is not a small feat. Patients in this study were heavily pre-treated, averaging 4 prior therapies, and platinum-resistant. This study exemplifies why clinical trials bring true hope to ovarian cancer patients. Although DMUC5754A must still prove its value in phase II and III trials, results from this phase I trial are hopeful.
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