Since she enrolled in a clinical trial at MSK to treat her low-grade serous ovarian cancer, Ellen Coopersmith has a new outlook on life.
The first drug for a rare and difficult-to-treat type of ovarian cancer has been granted accelerated approval by the Food and Drug Administration (FDA). The treatment, called avutometinib plus defactinib (Avmapki Fakzynja Co-pack), was developed to treat low-grade serous ovarian cancer (LGSOC).
The phase 2 clinical trial that resulted in the approval was led in the United States by gynecologic medical oncologist Rachel Grisham, MD, of Memorial Sloan Kettering Cancer Center (MSK). Dr. Grisham is also leading the global randomized confirmatory phase 3 trial that is currently ongoing.
“This new treatment, which combines two different targeted therapies, is based on research that was done in MSK labs about a decade ago,” Dr. Grisham says. “The story of how this treatment came about illustrates the importance of continuing to do lab-based research.”
What Is Low-Grade Serous Ovarian Cancer?
LGSOC accounts for less than 10% of all cases of ovarian cancer. It is more common in younger women. The average age at the time of diagnosis is about 55, but unlike more common types of ovarian cancer, many women are diagnosed in their 20s or 30s.
As the words low grade suggest, LGSOG is considered less aggressive than other types of ovarian cancer. That’s mainly because it grows more slowly. Patients diagnosed with this cancer tend to live longer, even when the cancer has spread.
However, it is also less likely to respond to chemotherapy. In fact, chemotherapy is effective in fewer than one in 20 patients with LGSOC.
One Patient’s Dramatic Response
Ellen Coopersmith, a 62-year-old retired kindergarten teacher from the Philadelphia area, is participating in the phase 3 trial of the therapy. Since she began taking the drug in January 2025, her cancer has shrunk by 70%. Tests show her tumor marker has normalized, and she feels great.
“Compared to how I felt after chemotherapy and surgery, this is a walk in the park,” Ellen says. “It’s really amazing. Other than feeling a little tired, I really don’t have any side effects.”
Results of the Phase 2 Trial for Avutometinib-Defactinib Combination
Ellen is not the only patient to respond well to the treatment. Overall, 44% of patients with a KRAS mutation in the phase 2 trial saw their tumors shrink, according to findings Dr. Grisham presented at the Society of Gynecologic Oncology Annual Meeting in March 2025.
All the patients in the study had previously been treated with at least one line of chemotherapy and had recurrent, measurable disease.
“This treatment has shown unprecedented response rates for patients who currently have few good options,” says Dr. Rachel Grisham, who is leading clinical trials on avutometinib plus defactinib.
The highest response rates were seen in patients who tumors harbored a mutation in the gene KRAS — a mutation found in about one-third of LGSOC cases — and the new treatment was FDA approved specifically for patients whose cancers have that mutation. But there were still responses in patients without KRAS mutation, just at a lower rate. This group is being further studied in the ongoing phase 3 study. Ellen does not have the KRAS mutation, but her cancer has defects in a related gene.
“This treatment has shown unprecedented response rates for patients who currently have few good options,” Dr. Grisham says. “The combination works much better than the current standard treatments for this disease, which are either chemotherapy or endocrine [hormone] therapy.”
Some patients in the trial had side effects. Some of the most common ones were:
- Fatigue
- Gastrointestinal problems
- Rash
- Changes in blood counts
Avutometinib and defactinib are taken as pills. Avutometinib is taken twice a week and defactinib is taken twice a day. Patients take them for three weeks, then pause for a week before resuming that schedule.
A Targeted Therapy Approach Based on MSK Lab Research
Both drugs are targeted therapies. Avutometinib blocks two pathways responsible for cancer growth — called MEK and RAF; defactinib blocks FAK.
The lab of MSK physician-scientist David Solit, MD, was the one of the first to make the connection between MEK mutations and ovarian cancer. In 2015, the team published a paper in the Journal of Clinical Oncology that showed how defects in the MEK protein drive the growth of LGSOC. Dr. Grisham was first author, and Dr. Solit and MSK genitourinary medical oncologist and early drug development specialist Gopa Iyer, who was then a member of Dr. Solit’s lab, were senior authors.
Since then, drugs that block MEK have been used to treat LGSOC with some success, but none have been FDA approved for that purpose. Later studies from other labs found that blocking FAK as well as MEK made this approach more effective and longer-lasting.
The MEK and FAK pathways act “downstream” from KRAS — a class of proteins that are responsible for many types of cancer. Because the KRAS protein is difficult to block, Dr. Grisham, Dr. Solit, and their colleagues believe this combination approach is likely to be more effective.
A Clinical Trial Gives Ellen a New Outlook on Life
Ellen was first diagnosed with stage 3 LGSOC in 2016. Her husband had recently died, and her three children were in high school. She had surgery at a hospital near her home, but when she learned she would need more treatment, she went to MSK.
“I needed to go to where I could get the best doctor with the best care,” she says. “I couldn’t die — I knew I had to beat this. I feel very fortunate that I became Dr. Grisham’s patient.”
In between her first surgery and her enrollment in the trial, Ellen had other treatments, including several additional operations, which were done by MSK gynecologic surgeon Yukio Sonoda, MD, FACOG, FACS.
“Cancer is brutal, and some of the surgeries for ovarian cancer can really prevent you from living your life,” Ellen says. “What I love the most about my doctors at MSK is that they care about not only the quantity of life, but the quality of life that you have. Dr. Sonoda is a wonderful surgeon. He was always mindful of how important it was for me to stay mobile and active.”
Ellen appreciates that her MSK doctors have focused on maintaining her quality of life throughout her treatments.
In 2022, Ellen began receiving chemotherapy, which was not effective. Then she learned about the clinical trial. “I was very excited when I found out I could get into this trial,” Ellen says. ”Dr. Grisham knows me, she understands the genetics of my disease, and she knows what my body needs in order to fight this. And she was involved in the research from the very beginning, so I felt confident that she would be able to help me with any side effects that came up.”
“This FDA approval means that patients with LGSOC now have a really good option for treating their cancer,” Dr. Grisham says. “We expect this therapy will become the new standard of care for LGSOC patients with KRAS mutations.”
For Ellen, who will continue participating in the phase 3 trial, the treatment has given her a new outlook on life.
“When you’re first diagnosed with cancer, you just stop and think, OK, how many years do I have left, and what do I need to get done in those years?” Ellen says. “I never thought my life would be extended like this. I could not be any luckier. Now it’s exciting to think, maybe I’ll get to meet my grandkids.”
