Unpacking the Complexities of a Rare Ovarian Cancer

Unpacking the Complexities of a Rare Ovarian Cancer

By Dan Paterson, President & CEO, Verastem Oncology

Ovarian cancer has long been a challenge to treat, as the disease is often diagnosed late due to its varied progression patterns and symptoms that can be hard to recognize initially. However, needed clarity came when the disease was recognized not as a single entity, but as different cancers with distinct biological and molecular characteristics, leading to the separation of low-grade serous ovarian cancer (LGSOC) from its high-grade counterpart (HGSOC). 

This distinction was an essential first step towards tailoring the right solutions for these patients. However, defining the problem was just the beginning. 

The Unique Challenges of LGSOC

While LGSOC accounts for less than 10% of ovarian cancer cases, its impact is profound, particularly on younger women who frequently confront added challenges, such as fertility concerns and early menopause.

Treating patients with LGSOC is challenging, as it is typically resistant to chemotherapy and has a high recurrence rate. But there is now renewed hope for development of better targeted therapies with the recognition that LGSOC is mainly driven by alterations in the RAS pathway, a key regulator of cancer cell proliferation that can turn malignant and evade therapeutic targeting.

Diagnosing LGSOC is also difficult, as its symptoms are often mistaken for other conditions, which can lead to a frustrating and drawn-out journey for patients to even obtain a diagnosis. Further, the fact that LGSOC can occur in younger women than its high-grade counterpart adds to the challenge of accurate diagnosis. So, with thousands of new cases emerging annually in the United States and a community mobilized for change, there’s a pressing need for earlier recognition and diagnosis and tailored treatment options for these patients.

Now, it is our mission to turn potential into new therapeutic options for these patients.

Unique Complexities Require Unique Solutions

At Verastem Oncology, we are deeply committed to overcoming the challenges of LGSOC and proud of the significant progress we have made. Notably, our combination of avutometinib with defactinib has shown promising clinical results and received a Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for recurrent LGSOC. This combination is designed to work together to inhibit multiple components of the malignant RAS pathway and surrounding signaling pathways to combat drug resistance and halt cancer growth. 

In our RAMP 201 Phase 2 trial, the combination of avutometinib with defactinib showed an encouraging objective response rate for patients with recurrent LGSOC, suggesting that this combination could be a viable treatment option for women with this hard-to-treat cancer and potentially the first therapy ever approved specifically for patients with LGSOC.

Based on these findings, we are preparing for the upcoming global confirmatory RAMP 301 Phase 3 trial, an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT), which will further evaluate the efficacy and safety of avutometinib and defactinib against standard-of-care chemotherapy and hormonal therapy in patients with recurrent LGSOC.

We’re Stronger Together

Addressing the complexities of ovarian cancer also requires cultivating deep, meaningful connections and providing unwavering support to the ovarian cancer community.

Too often we would hear from the LGSOC community that more education and discussion need to happen about the disease and that LGSOC patients frequently have to do their own research to better understand their diagnosis. In an effort to better serve patients with LGSOC, as well as their families and caregivers, Verastem Oncology launched the “Let’s Talk About LGSOC initiative in March. Developed in close collaboration with clinicians, patients, and advocacy leaders, this initiative provides comprehensive resources that cover the complexities of LGSOC, its symptoms, how it differs from HGSOC, and ways to connect with others in the LGSOC community. And we are looking forward to making a physician-directed initiative available before the end of the year to support those interactions between patients and their oncologists around this rare ovarian cancer for which they might not have had a deep level of first-hand experience.

In alignment with these efforts, we prioritize incorporating voices from the LGSOC community into the design of our clinical trials. Most recently, we sought feedback from patient advocates to shape the design of our upcoming RAMP 301 trial.

We’re further amplifying the voices of those impacted by LGSOC with a first-of-its-kind, multi-national LGSOC Patient Impact Survey among people diagnosed with LGSOC. Created with leaders from the medical and advocacy communities, including STAAR Ovarian Cancer Foundation, Cure Our Ovarian Cancer, and World Ovarian Cancer Coalition, this global survey reveals the particular challenges with diagnosis, disease management and mental, physical, and emotional well-being experienced by people living with LGSOC. By hearing directly from the people affected by this rare and difficult-to-treat disease, we hope these findings will help drive action and important dialogue to better serve and support patients throughout their journey.

So, whether it’s through our progressing clinical trials or our extensive LGSOC community engagement initiatives, we are proud to continue serving the LGSOC community on every level. I firmly believe that by bridging innovative research with robust community engagement, we create an empowering environment where those impacted by LGSOC feel heard, understood and supported. 

It is in this space that we can truly unpack the complexities of a rare ovarian cancer and work to finally turn potential into desperately needed new therapies for those affected by this disease.