Despite treatment, the survival rates for women with ovarian cancer remain poor, and the chance of the cancer returning is high. But there could be hope for women whose cancer has returned following chemotherapy in the form of a promising cancer-fighting drug that is currently undergoing clinical trials in the US.
The drug, called upifitamab rilsodotin, is an antibody-drug conjugate, a class of drugs designed as targeted therapy for disease treatment. Upifitamab rilsodotin acts like a Trojan horse, tricking its way into ovarian cancer cells to deliver its cancer-destroying treatment. It has been used to successfully treat other types of cancer.
“Imagine the cancer cell as a circle,” said Dr Amanda Jackson, a physician-researcher at the University of Cincinnati and the principal investigator for the UP-NEXT trial. “Then imagine it having tiny bumps on the surface, those bumps would be the antigens. 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.”
Ovarian cancer has a reputation for being a “silent killer” because symptoms develop only after the disease is at an advanced stage and is largely incurable. Despite intervention with treatments like chemotherapy, the disease has a low survival rate and is prone to recur. According to the Ovarian Cancer Research Alliance, around 70% of women diagnosed with ovarian cancer will have a recurrence.
“While we’ve made great strides in improving care, the overall survival rate is still only about 45% for ovarian cancer,” Jackson said.
Phase 3 trials use two groups of patients to test the safety and effectiveness of new treatments compared to standard treatments. For example, a phase 3 trial can determine which group of patients has better survival rates or fewer side effects.
The UP-NEXT trial is a multi-center randomized trial that hopes to enroll 350 patients across all locations. Eligible patients will either receive intravenous upifitamab rilsodotin or a placebo every four weeks after completing a round of chemotherapy treatment.
“The 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 trial is targeting patients whose ovarian cancer has returned following treatment with platinum-based chemotherapy drugs. Platinum-based drugs such as cisplatin, carboplatin, and oxaliplatin are widely used to treat cancer. However, their clinical application can be limited by side effects such as toxicity and drug resistance.
Women whose cancer returns less than six months after platinum-based chemotherapy are deemed to be platinum-resistant. If it returns more than six months post-chemotherapy, they are regarded as platinum sensitive.
Platinum-resistant ovarian cancers tend to be less responsive to chemotherapeutic treatment. However, given that upifitamab rilsodotin has already shown positive results in patients with platinum-resistant ovarian cancer, the UP-NEXT trial is testing the drug's effectiveness in platinum-sensitive 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. “This is our only platinum-sensitive study open. 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.”
The discovery of the BRCA gene mutation and its link to cancer has led to breakthroughs in treating ovarian cancer. But, not many trials focus on women without the BRCA mutation. Hence the importance of the UP-NEXT trial.
“This study is so important because it provides a unique treatment opportunity for patients who have access to very few clinical trials,” Jackson said. “We’re excited about the chance to introduce a new maintenance drug that could potentially offer a significant benefit to another group of patients.”
Source: University of Cincinnati
