Desmoid Tumors:
An Overview

What is a desmoid tumor?

Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are rare, locally invasive and often debilitating and disfiguring soft-tissue tumors. While they can arise in any part of the body, the most common sites are the upper extremities (arm, forearm, and hand), lower extremities (hips, thigh, leg, and foot), abdominal wall, head and neck. Desmoid tumors can cause significant morbidities, including severe pain, internal bleeding, incapacitating loss of range of motion, and, in rare cases, death.

CLINICAL REPRESENTATION OF
DESMOID TUMORS

HEAD& NECK

Head and neck with desmoid tumorHead and neck with desmoid tumor

UPPER
EXTREMITIES

Forearm and hand with desmoid tumorForearm and hand with desmoid tumor

LOWER
EXTREMITIES

Thigh and leg with desmoid tumorThigh and leg with desmoid tumor

X-ray of abdominal wall with desmoid tumorX-ray of abdominal wall with desmoid tumor

THORACIC

X-ray of abdominal wall with desmoid tumorX-ray of abdominal wall with desmoid tumor

INTRA-ABDOMINAL / ABDOMINAL WALL

What causes desmoid tumors?

While the cause of most desmoid tumors is unknown, most desmoid tumors have mutations in a gene called catenin beta-1, which controls activity of other genes; promotes growth, activity, and division of cells; and helps cells stick together to form tissues. Other desmoid tumors are caused by mutations in a gene called APC that causes Familial Adenomatous Polyposis (FAP). People with FAP are at high risk of developing abdominal desmoid tumors.

Who is at risk for desmoid tumors?

While desmoid tumors can occur in people between 15 and 60 years of age, they are more commonly diagnosed in young adults between 30-40 years of age. Women are also 2 to 3 times more likely to develop them than men. It is estimated that there are 1,000 to 1,500 new cases diagnosed each year in the United States.

How are desmoid tumors treated?

There are currently no medicines approved for the treatment of desmoid tumors. Historically, desmoid tumors were treated with surgical resection, but this approach has become less favored due to a high recurrence rate after surgery. Doctors may also use systemic therapies, including chemotherapies, off-label to treat desmoid tumors. SpringWorks is testing a gamma secretase inhibitor called nirogacestat in a Phase 3 clinical trial known as the DeFi trial.

DeFi Trial Overview

What is the DeFi trial?

The DeFi (Desmoid/Fibromatosis) trial is a Phase 3 clinical trial designed to evaluate the safety, efficacy, and tolerability of an investigational medicine called nirogacestat in people over the age of 18 with progressing desmoid tumors. Nirogacestat is an oral, small molecule inhibitor of gamma secretase – in other words, a pill that is designed to inhibit a protein in the body that is known to contribute to desmoid tumor growth.

The DeFi trial is a double-blind, placebo-controlled study, meaning that people are sepa­rated into two groups: one that receives nirogacestat, and one that receives a placebo, a pill or substance with no active ingredients that is not expected to have any medical effect on a study participant. Neither the study participant nor the doctor knows the group to which the person is assigned.

How long the study lasts:

The double-blind phase of the DeFi trial will run for approximately 2 years. If a desmoid tumor is progressing while participating in the double-blind phase or the double-blind phase has completed, there is an optional open-label extension phase of the study. Those who qualify for the open-label extension will receive treatment with nirogacestat.

How often you need to be seen as part of the trial:

The clinical trial site will go over the details of the study, but following initial evaluation and visits to record your health at the start, most participants will begin taking a pill and be asked to return to the clinic for study visits on days 8, 15 and 22 of the first month, day 28 of the second month, day 1 of the fourth month, and then every 3 months after that.

What happens at each clinic visit:

Each visit will include a routine evaluation such as a physical exam and a check of your vital signs.

As part of the study, participants will also be asked to complete questionnaires, have scans (CT or MRI) to measure their tumor(s), and have blood drawn.

How Do I Know if I Qualify for the DeFi Trial?

People who have been diagnosed with a desmoid tumor and are interested in participating in this study should discuss it with their doctor. Only your doctor can determine if you meet the eligibility requirements, some of which include:

Eligibility requirements1/4

How to Get Involved in the DeFi Trial

If you or a loved one is interested in participating in the DeFi trial, please talk to your doctor to determine if you are eligible for the study.

For medical professionals seeking additional information about the DeFi trial, please email clinical@springworks.com.

The DeFi trial will be conducted in approximately 60 sites in the U.S., Canada and Europe. Details of the trial locations can be found here.