A Potential New Benchmark in Platinum‑Resistant Ovarian Cancer Treatment
- Early data show the cancer drug mocertatug rezetecan (Mo‑Rez) delivering response rates above 60% in patients with ovarian and endometrial cancers that have returned after earlier treatment (recurrence).
- While Mo-Rez is still early in its development, the Phase 1 BEHOLD-1 clinical trial data is a major step forward, considering the standard treatment, a single-agent chemotherapy, for recurrent ovarian and endometrial cancer yields an objective response rate of only “5 to 15%,” says Dr. Sarah Taylor, Director of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh and Magee-Womens Hospital of UPMC.
- BEHOLD‑1 trial is evaluating Mo‑Rez, a B7‑H4–targeted antibody‑drug conjugate, meaning it works by delivering chemotherapy directly to cancer cells.
- The low response rate of standard treatments is what makes the promise of Mo-Rez “truly inspiring to see,” says Dr. Amy Armstrong, Division Chief, Gynecologic Oncology at UH Seidman Cancer Center.
- Experts say early results from BEHOLD-1 offer real hope for patients with high unmet need, leading Dr. Bhavana Pothuri, director of Gynecologic Oncology Clinical Trials at NYU Langone Health, to eagerly await “the phase 3 trials in both ovarian and endometrial cancer in hopes of bringing Mo‑Rez quickly to patients across the world.”
The promising results Mo-Rez has shown in recurrent ovarian and endometrial cancers are generating rare optimism among experts, who tell SurvivorNet that these cancers have long been defined by limited treatment options and may finally be gaining real momentum.
Read More“The study target applies to about 95 percent of these patient types (tumor agnostic/all comers), which is encouraging news for patients,” said Dr. Premal Thaker, a gynecologic oncologist and surgeon at Siteman Cancer Center at WashU Medicine.
Although Mo-Rez’s journey toward approval is only in phase one, there is a lot of optimism among clinicians.
Dr. Sarah Taylor, Director of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh and Magee-Womens Hospital of UPMC, notes that antibody drug conjugate development is accelerating due to “well‑characterized cell surface antigens, high unmet need in recurrent or treatment‑resistant disease, and an increasing emphasis on biomarker‑directed therapy.”
She explains that B7‑H4, a co‑inhibitory immune checkpoint ligand, is highly expressed across gynecologic cancers, especially ovarian and endometrial tumors, while showing minimal expression in normal tissues, making it an appealing therapeutic target.
Mo‑Rez pairs an anti–B7‑H4 antibody with a topoisomerase I inhibitor payload, a design intended to deliver potent chemotherapy directly to cancer cells.
WATCH: Chemotherapy for Ovarian Cancer
Strong Early Signals In a Difficult‑to‑Treat Population
According to data presented at the Society of Gynecologic Oncology (SGO) Annual Meeting, the drug manufacturer of mocertatug rezetecan, GSK, highlighted clinical trial progress in Puerto Rico this year.
In the phase 1 BEHOLD‑1 trial, Mo‑Rez demonstrated notably high response rates in heavily pretreated patients.
According to data presented at SGO, GSK reported that at the highest doses tested:
- 62% of patients with platinum‑resistant ovarian cancer achieved confirmed objective responses, which means study participants who have a partial response or complete response to the treatment within a certain period of time.
- 67% of patients with recurrent or advanced endometrial cancer responded to treatment
These cancers typically have very limited treatment options, and response rates to existing later‑line therapies are modest.
“Platinum‑resistant ovarian cancer and advanced endometrial cancer can be difficult to treat with overall low response rates to later‑line therapies,” Dr. Parker said.
“This trial found an over 60% response rate in both cancer types with this medication, with manageable side effects,” Dr. Parker said.
The most common side effect reported was nausea, and overall toxicity was described as manageable.
“The toxicities reported were not meaningfully different from active agents in the same space,” says Dr. Whitfield Growdon, a Gynecologic Oncologist at NYU Langone, who tells SurvivorNet.
Dr. Bhavana Pothuri, director of Gynecologic Oncology Clinical Trials at NYU Langone Health, emphasizes that these responses occurred in patients who had already received a median of two prior lines of therapy, adding that Mo‑Rez “appears well‑tolerated with a low discontinuation rate.”
How Mo‑Rez Compares to Current Benchmarks
Dr. Taylor notes that standard single‑agent chemotherapy in these settings typically yields objective response rates of only 5–15%. The low response rate of standard treatments is what makes the promise of Mo-Rez “truly inspiring to see,” says Dr. Amy Armstrong, Division Chief, Gynecologic Oncology at UH Seidman Cancer Center.
Recent advances have raised the bar:
- Mirvetuximab soravtansine (Elahere) achieved a 42.3% response rate in FRα‑high platinum‑resistant ovarian cancer in the phase III MIRASOL trial.
- In endometrial cancer, lenvatinib + pembrolizumab, a current standard, produced 30–35% response rates in previously treated advanced disease (KEYNOTE‑775).
Against that backdrop, the early Mo‑Rez data stand out.
“Treatment of platinum-resistant ovarian cancer is one of our most difficult scenarios,” and the early results are giving oncologists “a sense of hope for the future,” Dr. Armstrong added.
WATCH: Genetic Testing for Ovarian Cancer
What Comes Next
“These results represent exceptionally encouraging phase I data and suggest that B7‑H4–targeted ADCs may define a new efficacy benchmark for heavily pretreated gynecologic cancers,” Dr. Taylor says.
Clinicians across institutions echo the optimism while stressing the need for continued follow‑up.
“I am excited about the phase 3 trials in both ovarian and endometrial cancer in hopes of bringing Mo‑Rez quickly to patients across the world,” says Dr. Pothuri.
“Further studies are in progress, which will hopefully lead to FDA approval of this new antibody-drug conjugate and give clinicians another effective option for our patients who suffer from these diseases,” says Dr. Ronald Alvarez, Chairman of Obstetrics & Gynecology, Vanderbilt-Ingram Cancer Center.
Expert Resources to Help Ovarian Cancer Patients Facing Recurrence
The Standard of Care for Ovarian Cancer
The standard of care for ovarian cancer patients is chemotherapy, which helps many patients reach remission when signs of cancer are no longer detected.
WATCH: How to Manage Recurrence of Ovarian Cancer.
With recurrence a strong possibility for this disease, especially in the later stages of ovarian cancer, certain drug treatments to deal with it are giving many women hope.
Maintenance therapy is continued treatment after the patient finishes their initial treatment. After an ovarian cancer patient completes a round of treatments, such as surgery and chemotherapy, her doctor may recommend some form of maintenance therapy to try to delay possible recurrence.
Maintenance therapy can involve taking an oral pill called a PARP inhibitor every day after chemotherapy and can keep cancer in remission longer.
The type of treatment recommended for recurrence can depend on several factors:
- The period within which the cancer recurred
- The kind of chemotherapy the woman underwent in the past
- Side effects that came as a result of past treatments
- The length of time between the last treatment the woman underwent and the recurrence
- The specific mutations and molecular features of your cancer
What’s the Standard of Care for Ovarian Cancer Recurrence?
Ovarian cancer recurrence happens in “almost 25 percent of cases with early-stage diseases and in more than 80 percent with more advanced stages,” according to research published in the Gland Surgery medical journal.
In many cases, platinum-based chemotherapy is an effective starting point for multiple cycles. As the cancer cells develop resistance, a different approach is explored between the patient and her care team.
Platinum Sensitivity vs. Resistance: What It Means for Treatment
- Platinum Sensitive: If a patient remains cancer-free for more than six months after platinum therapy, they’re considered platinum sensitive. This signals that the cancer is still responding, and doctors may continue using platinum-based drugs.
- Platinum Resistant: If recurrence occurs within six months, the cancer is classified as platinum resistant. In these cases, oncologists typically shift to alternative therapies tailored to overcome resistance.
Adjusting Chemotherapy Strategies
- Taxol (Paclitaxel): Commonly paired with platinum in initial treatment. For platinum-resistant patients, doctors may increase its frequency—administering it weekly instead of every three weeks.
- Other Options: Drugs like Gemzar (gemcitabine), Topotecan, and Doxil (liposomal doxorubicin) are often introduced, sometimes alongside Avastin (bevacizumab).
Better Understand Endometrial Cancer
Endometrial cancer begins when cancerous cells form in the tissues of the endometrium, the inner lining of the uterus.
WATCH: Different Types of Endometrial Cancer
Some common risk factors for endometrial cancer include:
- Obesity
- Taking estrogen-only hormone replacement therapy after menopause
- Having never given birth or started menstruation at an early age
- Having a family history of endometrial cancer
Common symptoms of endometrial cancer may include:
- Pelvic pain: Some women may experience pain or discomfort in the pelvic area.
- Pain during intercourse: This symptom is less common but can occur in some cases.
- Unusual vaginal discharge: Watery or blood-tinged discharge may be a sign of endometrial cancer.
- Weight loss: Unexplained weight loss can sometimes be associated with cancer.
- Urinary problems: Difficulty or pain when urinating.
Endometrial Cancer Treatment Options
Treatment for endometrial cancer includes surgery, radiation, chemotherapy, hormone therapy, and targeted therapy. Surgery is the most common treatment method.
“There are a lot of new exciting treatments for advanced endometrial cancer that we’ve just discovered over the last couple of years,” Dr. Dana Chase, gynecologic oncologist at the David Geffen School of Medicine at UCLA, says.
“So even if you’re diagnosed with an advanced stage, ask your treating doctor what the latest treatments are, or even potentially, is there a clinical trial I can participate in for my endometrial cancer? … There’s a lot of research on new treatments for endometrial cancer, which is very exciting,” Dr. Chase continued.
The most common procedure is a hysterectomy, where the surgeon removes the uterus. They often also remove both ovaries and fallopian tubes in bilateral salpingo-oophorectomy. This helps lower the risk of the cancer spreading or coming back.
WATCH: What to Know About Endometrial Cancer-Related Surgery
“Doctors usually treat early-stage endometrial cancer with surgery as the main approach,” Dr. Rimel explains. “During the surgery, doctors may also perform staging to see how far the cancer has spread. This involves taking out and examining nearby lymph nodes and tissues.”
Chemotherapy and radiation are options, particularly when the cancer is in more advanced stages.
Treating endometrial cancer with hormone therapy involves removing hormones or blocking their ability to help cancer cells grow. Targeted therapy treatment uses drugs designed to target specific cancer cells.
“Hormonal therapy commonly works because most endometrial cancers are estrogen receptor-positive,” Dr. Michael Toboni, an assistant professor in the division of gynecologic oncology at the University of Alabama at Birmingham, tells SurvivorNet.
“So if you give progesterone, it can counteract the estrogen feeding the cancer. This is commonly given with multiple anti-estrogen medications or an anti-estrogen medication in combination with another medication that inhibits a common pathway in endometrial cancer.”
Each treatment method can have side effects, and the impact on the body may vary by treatment type. If you are undergoing treatment for endometrial cancer, discussing potential side effects with your doctor and strategies to minimize their impact is crucial.
Existing Treatment Options for Advanced and Recurrent Endometrial Cancer Patients
The U.S. Food and Drug Administration (FDA) approved combination therapy for advanced or recurrent endometrial cancer to be used with traditional chemotherapy is dostarlimab-gxly (brand name Jemperli). It is an immune checkpoint inhibitor, a type of immunotherapy that helps reinvigorate the body’s immune system to fight cancer.
WATCH: Treatment for Advanced or Recurrent Endometrial Cancer
Dostarlimab-gxly was already approved for metastatic and recurrent endometrial cancer in cases where chemotherapy did not work. Dostarlimab-gxly is approved as a first-line treatment for patients with a specific set of genetic mutations known as mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). These genetic factors are associated with a much greater response to checkpoint inhibitor drugs. Patients should ask their doctor about genetic testing to learn if they carry any such mutations.
WATCH: A New Wave of Cancer Patients Using SurvivorNet’s My Health AI Tools For Support
Questions for Your Doctor
If you’ve been diagnosed with ovarian cancer and are looking for ways to better understand your disease and treatment options, here are some key questions to bring to your doctor.
You can also turn to SurvivorNet’s proprietary AI tool, “My Health Questions“, which helps patients and caregivers navigate a new diagnosis and prepare thoughtful, personalized questions for their care team.
- What type of ovarian cancer do I have?
- What stage is my cancer in?
- Do you recommend I get genetic testing for any gene mutations, such as the BRCA gene mutation?
- What initial treatment options do you recommend?
- What are the possible side effects of the recommended treatment, and how can they be coped with?
- Will insurance help cover my recommended treatment?
Learn more about SurvivorNet's rigorous medical review process.
