Antibody drug conjugates make strides in ovarian cancer with recent FDA approval

BYLINE: Denise Heady

Newswise — Ovarian cancer can be a very difficult disease to treat, and until recently, had not benefited from new treatments for more than 40 years.

Most cases of ovarian cancer are diagnosed at more advanced stages, when the disease has already spread throughout the body, and survival rates are not great: Just about 50% of patients survive five or more years.

The UCLA Health women’s cancer research team in OBGYN is trying to change that by working toward finding new and better ways to treat this often-deadly disease and other gynecologic malignancies.

Most recently, the team played a pivotal role in a clinical trial that led to the FDA granting accelerated approval of the first antibody drug conjugate (ADC), mirvetuximab soravtansine, for the treatment of platinum-resistant ovarian cancer.

Antibody drug conjugates are a type of targeted cancer therapy designed to deliver anti-cancer drugs directly to cancer cells while minimizing damage to healthy cells.

“This type of therapy allows us to give chemotherapy in a targeted way,” said Gottfried Konecny, MD, professor of hematology/oncology at the David Geffen School of Medicine at UCLA and member of the UCLA Health Jonsson Comprehensive Cancer Center. “It’s an antibody that binds to a tumor-specific protein, and it’s attached to a payload that only delivers the drug to the cancer cells, potentially reducing harmful side effects in healthy tissues.” 

While ADCs have been developed and approved for the treatment of other cancer types, it wasn’t until recently that use of these drugs for one of the hardest cancers to treat was explored.

Clinical trial results show significantly longer overall survival

Known as the MIRASOL trial, the clinical trial evaluated mirvetuximab soravtansine, an ADC designed to target folate receptor alpha, to treat platinum-resistant ovarian cancer, the deadliest gynecologic cancer. 

The trial included 453 participants from 253 clinical locations in 21 countries. The UCLA Health team enrolled 17 patients, making them the top enrolling center in the United States. 

“Being a top accruing site is not an easy feat,” said Jenny Lester, MPH, CCRP, director of clinical trials in obstetrics and gynecology, urology and surgery at the David Geffen School of Medicine. “Our clinical trial coordinators worked with multiple hospitals throughout the country to collect specimens and lab results to see whether a particular patient was even qualified to be in the study. The team was able to create a pipeline to get patients through that process as quickly as they could so that they could be treated, which contributed to the overall success of the clinical trial.”

The patients in the trial were randomly divided into two groups, with 227 receiving the ADC and 226 receiving regular chemotherapy.

The researchers found that 42% of people given the ADC saw their tumors shrink, whereas only 16% of people on chemotherapy saw tumor shrinkage.

People given the ADC also lived longer, with a median survival of nearly 17 months, compared to nearly 13 months for those on chemotherapy. The ADC group also experienced fewer and less serious and serious side effects.

The results were published in the New England Journal of Medicine in December 2023.

“Platinum-resistant ovarian cancer is just a terrible disease,” said Dr. Konecny, who was an author on the study. “We found that this drug improves survival in patients with this disease and was wonderfully well tolerated with less toxicity and no hair loss. We saw very little fatigue in patients and no nausea. Patients are excited because they can continue to have a good quality of life, and being able to extend someone’s quality of life is significant.”

What’s next?

The team is now working on developing this drug further with a companion study looking at platinum-sensitive disease and the first combination study of ADCs with carboplatin, another type of platinum-based chemotherapy.

In addition, the women’s cancer research team in OBGYN is actively recruiting participants in more than 60 clinical trials that are exploring new treatments to improve outcomes in ovarian cancer.