UP-NEXT study tests ovarian cancer treatment

“While we’ve made great strides in improving care, the overall survival rate is still only about 45% for ovarian cancer,” said the University of Cincinnati’s Amanda Jackson, MD. 

Jackson is the site principal investigator at UC for the UP-NEXT trial that is testing a new treatment for a subset of ovarian cancer patients.

Jackson said the trial is testing the effectiveness of an antibody-drug conjugate (upifitamab rilsodotin) that is part of a class of therapeutics that have proven to be successful treatments for other types of cancer. The drug works as a kind of Trojan horse, binding to a specific antigen often found on the surface of ovarian cancer cells. 

“Imagine the cancer cell as a circle. Then imagine it having little tiny bumps on the surface, those bumps would be the antigens,” said Jackson, University of Cincinnati Cancer Center physician-researcher and associate professor, division chief and vice chair in the UC College of Medicine’s Department of Obstetrics & Gynecology. “In patients that have this specific antigen on their ovarian cancer cells, the drug binds to that antigen. It basically tricks the cell into letting it bind, and when it does that, it releases a payload of drug into the cell that kills it.” 

Eligible patients will be randomly assigned to either receive the study drug or a placebo in the phase 3 trial. The drug is delivered through an IV every four weeks about a month after finishing a round of standard chemotherapy treatment. 

“This drug is considered a maintenance medication,” Jackson said. “We’re looking to see how well this drug works and is it going to change outcomes. Specifically it’s looking to see how long we can keep people’s cancer at bay without it coming back.” 

The study is scheduled to enroll 350 patients at all trial locations, and Jackson said she hopes to enroll at least five patients per year at UC while the study is open.

When ovarian cancer returns following initial treatment with platinum-based chemotherapy treatments, Jackson explained patients are divided into two groups, platinum-resistant and platinum sensitive. Patients whose cancer recurs more than six months past their chemotherapy are designated as platinum sensitive, while those whose cancer returns before six months are platinum-resistant. 

Jackson said platinum-resistant ovarian cancers tend to be less responsive to chemotherapy and are more difficult to treat. Because of this, most ovarian cancer research focuses on platinum-resistant patients. 

“We usually start with the platinum-resistant group, and if you can prove that platinum-resistant patients can get benefit from this drug, then we keep moving it up further and further up the list to see if we can get a better impact,” Jackson said.

The UP-NEXT study drug has shown positive results in patients with platinum-resistant ovarian cancer, so the trial is testing the effectiveness in those patients. 

“This is our only platinum-sensitive study open. It tends to be an area where we don’t have a lot of clinical trials because it takes a lot of work to get to this level,” Jackson said. “When we get a drug at this level, we’re really excited about it because there’s a really good chance that it could change how we treat patients in the future.” 

Jackson said there have been significant recent treatment breakthroughs for ovarian cancer patients with a specific mutation called BRCA, but there is still an unmet need for the majority of patients without the mutation. 

“We’re looking for a drug to be that next big thing that will help another group of patients have a better outcome,” she said. “This study is so important because it provides a unique treatment opportunity for patients who have access to very few clinical trials. We’re excited about the chance to introduce a new maintenance drug that could potentially offer a significant benefit to another group of patients.” 

The UP-NEXT trial is sponsored by Mersana Therapeutics. For more information on eligibility and enrollment, contact Margan Harris (harri3mm@ucmail.uc.edu) or Jessica Mullins (mullij3@ucmail.uc.edu).

Featured photo at top: ovarian cancer tumor in animal model. Photo/National Cancer Institute.