New Breakthroughs and Emerging Treatments for FR-Alpha–Positive Ovarian Cancer
Published on June 3, 2026
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Ovarian cancer treatment usually starts with surgery followed by chemotherapy. While chemotherapy is an important part of treatment, researchers are developing more targeted ways to treat ovarian cancer.
Platinum-based chemotherapy is often used to treat ovarian cancer, but over time — especially if the cancer has recurred — the tumor sometimes becomes resistant to treatment. This is when targeted treatments come into play for more personalized treatment. One target that researchers have focused on is a protein called folate receptor-alpha (FR-alpha or FR-α), which can be found at high levels on some cancer cells.
What Is FR-Alpha–Positive Ovarian Cancer?
FR-alpha–positive ovarian cancer means the tumor cells have high levels of the FR-alpha protein (called a biomarker) on their surface. This protein helps cells absorb folate, a vitamin they use to grow and divide.
While healthy cells have some FR-alpha on their surface, many ovarian cancer cells have much higher levels, says Sharyn N. Lewin, MD, the director of the division of gynecologic oncology at Holy Name Medical Center in Teaneck, New Jersey, and an assistant clinical professor in the Icahn School of Medicine at Mount Sinai Hospital in New York. This is particularly common in epithelial ovarian cancers, which make up the majority of ovarian cancer cases, and especially in high-grade serous ovarian cancer, the most frequently diagnosed subtype, she says.
How Doctors Test for FR-Alpha
To determine if a tumor is FR-alpha–positive, healthcare professionals test a sample of the cancer tissue using a method called immunohistochemistry (IHC). One IHC test approved by the U.S. Food and Drug Administration (FDA) uses special stains to highlight proteins in cancer cells under a microscope. A lab then looks at how many cells show the FR-alpha protein and how strong that signal appears.
FR-alpha testing can be done from tissue that was already collected, such as during surgery, though a new biopsy may sometimes be needed, says Colleen McCormick, MD, a board-certified gynecologic oncologist and assistant professor in the department of gynecology and obstetrics at Johns Hopkins Medicine in Baltimore.
What FR-Alpha Test Results Mean
The results are based on both the percentage of tumor cells that show the FR-alpha protein and how intense the staining appears under the microscope, says Dr. Lewin. When FR-alpha is present on 75 percent or more of tumor cells with moderate to strong staining intensity, it’s known as high expression, and the tumor is considered FR-alpha positive, she says. When fewer than 75 percent of tumor cells show the protein at that level of intensity, the result is considered negative.
The level of FR-alpha expression helps guide treatment decisions, especially if the cancer becomes resistant to platinum, meaning it stops responding to platinum-based chemotherapy like carboplatin (Paraplatin), or returns within six months after treatment.
People with platinum-resistant ovarian cancer and high FR-alpha expression may be candidates for newer targeted therapies, and testing for this protein is the first step in finding out whether these treatments may be an option.
Many cancer centers perform FR-alpha testing when you’re first diagnosed, says Lewin, so if the cancer becomes platinum resistant later, those results are already available to help plan the next step in treatment.
Antibody-Drug Conjugates
One of the most significant breakthroughs in treating FR-alpha-positive ovarian cancer is a class of drugs called antibody-drug conjugates (ADCs). These treatments combine a lab-made antibody (a protein that the immune system uses to identify and latch onto specific targets) with a chemotherapy drug.
Once the antibody part of the ADC finds its target on the cancer cell — in this case, the FR-alpha biomarker — it attaches to it, like a lock and key, says Dr. McCormick. The chemotherapy drug in the ADC is then released inside the cell directly to damage or destroy it.
“This way, we can give treatments that are more targeted, with more toxicity on cancer cells and often less toxicity on the body,” McCormick says.
Together, they help deliver chemotherapy more precisely to cancer cells, says Joshua G. Cohen, MD, medical director of the gynecologic cancer program at City of Hope Orange County in Irvine, California.
FDA-Approved ADC
The only FDA-approved ADC for FR-alpha–positive platinum-resistant ovarian cancer is mirvetuximab soravtansine-gynx (MIRV), sold as the brand name Elahere. You may be eligible for this treatment if you’ve received one to three prior treatments.
In a clinical trial involving 453 people with platinum-resistant FR-alpha–positive ovarian cancer, MIRV helped shrink the cancer in about 42 percent of people, compared with 16 percent of those receiving standard chemotherapy. Those treated with MIRV also lived longer, a median of about 17 months, compared with 13 months for those receiving standard chemotherapy.
Side Effects
Many of the side effects caused by MIRV are manageable, says Dr. Cohen. Some common side effects include:
- Eye symptoms, such as blurry vision, dry eyes, and light sensitivity
- Lung inflammation (pneumonitis), which can cause cough, shortness of breath, and low oxygen levels
- Nerve-related symptoms (peripheral neuropathy), such as tingling, numbness, and burning sensations in the hands or feet
- Nausea and diarrhea
Eye-related side effects are the most common, occurring in more than half of people receiving this treatment. “The blurry vision is temporary and will almost always resolve within two weeks of the therapy being stopped,” Cohen says. Patients are monitored closely during treatment, so any changes can be caught and addressed early. Some eye-related side effects may become serious, in which case the drug may need to be discontinued.
Emerging Treatments
MIRV is changing the outlook for many people with FR-alpha–positive ovarian cancer, and researchers are working on even more ways to treat this condition. These options are being tested in clinical trials, which are regulated studies in people that help determine whether a treatment is safe and how well it works before approval.
Trials are looking at using MIRV earlier in treatment, including before the cancer becomes platinum-resistant, says Lewin. Others are investigating new drug combinations and targeted therapies that may make more treatment options available, she adds. Some of these treatments are in the earlier phases of clinical trials that focus on safety and finding the right dose (phase 1 or 2). Others are in a later phase, phase 3, which compares new treatments with existing ones in larger groups of participants. The treatments being studied have not been approved by the FDA.
Sofetabart Mipitecan
Sofetabart mipitecan (LY4170156) is an ADC being studied for FR-alpha–positive ovarian cancer. Like MIRV, it targets the FR-alpha protein, but it uses a different chemotherapy drug.
So far, this medication appears to work in people with platinum-resistant ovarian cancer with all levels of FR-alpha expression. This may make it an option for people with lower FR-alpha expression who may not qualify for MIRV.
In January 2026, sofetabart mipitecan received the FDA's Breakthrough Therapy designation for certain people with platinum-resistant ovarian cancer, which can help speed up the development and review process. A large phase 3 trial is underway to compare it with current treatments.
MIRV Plus Bevacizumab
MIRV is approved for certain platinum-resistant cancers. But researchers are studying whether it could also help people with platinum-sensitive recurrent disease, says Lewin, meaning the cancer returned more than six months after platinum-based treatment.
One approach is a combination of MIRV and bevacizumab (Avastin), a drug that helps block the blood supply that tumors need to grow, says Cohen.
A phase 3 study is evaluating this combination in people with high FR-alpha expression and recurrent platinum-sensitive ovarian cancer.
The goal is to see whether continuing treatment with this combination after the initial therapy, known as maintenance therapy, can keep the cancer under control longer and delay it from coming back.
MIRV Plus Carboplatin
Another combination approach is MIRV and carboplatin. A phase 2 study is looking at this combination, followed by MIRV alone, for people with platinum-sensitive ovarian cancer. This combination could be another way to improve outcomes, and larger studies are needed for final results.
A separate phase 2 trial is studying this same combination in people who are newly diagnosed with advanced FR-alpha–positive ovarian cancer and are candidates for chemotherapy before surgery. This trial is looking at whether giving this combination treatment before and after surgery could improve outcomes for these patients.
Farletuzumab Ecteribulin
Farletuzumab ecteribulin (MORAb-202) is an ADC in clinical trials for platinum-resistant ovarian cancer. It uses an FR-alpha–targeting antibody but with a different chemotherapy drug than MIRV, says McCormick.
Phase 1 findings showed that depending on the dose, this treatment may help shrink tumors in some people with various levels of FR-alpha expression. With this therapy, lung inflammation has been a side effect that researchers are watching closely. Studies are ongoing to evaluate appropriate doses and treatment effectiveness.
ZW191
ZW191 is an FR-alpha–targeting ADC currently being studied in people with all levels of FR-alpha expression.
This treatment is designed to kill not just the targeted cancer cells but also nearby cells that may have little to no FR-alpha on their surface. This could help target more of the tumor, since not all cancer cells express the same amount of FR-alpha.
In March 2026, the FDA granted this treatment its Fast Track designation for platinum-resistant ovarian cancer. This program is meant to speed up the development and review of treatments that show promise for serious conditions, though it does not mean the drug is approved. ZW191 is in a phase 1 trial to evaluate safety and how well it works.
FR-Alpha Targeted Vaccines
Researchers are exploring vaccines that train the immune system to recognize and attack cancer cells carrying FR-alpha. These are called dendritic cell vaccines; they are made from a patient’s own white blood cells that are then processed in a lab.
When these cells are reintroduced into the body as vaccines, they help guide the immune system to target and attack cancer cells carrying FR-alpha.
Some clinical trials are testing this vaccine in people with ovarian cancer, including after initial treatment and when cancer has come back. Other studies are combining the vaccine with immunotherapy drugs like pembrolizumab (Keytruda) to help strengthen the immune response. These are in phase 1 and 2 trials.
Talking to Your Doctor
The growing number of clinical trials underway for FR-alpha-positive ovarian cancer is encouraging. Talk with your cancer care team about whether you may be a candidate for a clinical trial and how to enroll.
You can also search for studies through ClinicalTrials.gov, the National Cancer Institute, and major cancer centers like Memorial Sloan Kettering, Mayo Clinic and Johns Hopkins.
While many of these trials are in early phases, more research is happening in FR-alpha–positive ovarian cancer than ever before, which may help expand future treatment options.
The Takeaway
- Folate receptor-alpha–positive ovarian cancer means that the tumor cells have high levels of the FR-alpha protein on their surface, and testing for it can help guide treatment decisions.
- A class of treatments called antibody-drug conjugates helps treat FR-alpha–positive ovarian cancer by delivering chemotherapy directly into these cancer cells, with potentially fewer side effects than traditional chemotherapy.
- Mirvetuximab soravtansine-gynx is the only FDA-approved treatment for people with FR-alpha–positive platinum-resistant ovarian cancer.
- New FR-alpha targeted drugs, combinations, and immune-based treatments that may expand options for ovarian cancer care are being studied. Talk to your care team about whether you might be eligible for a clinical trial.
Resources We Trust
- Cleveland Clinic: Antibody-Drug Conjugates (ADCs)
- Mayo Clinic: Ovarian Cancer: New Treatments and Research
- American Cancer Society: Targeted Therapy for Ovarian Cancer
- National Ovarian Cancer Coalition: Breakthroughs in Ovarian Cancer Treatment and Clinical Trials
- National Cancer Institute: Clinical Trials Using Mirvetuximab Soravtansine
EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
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