Nirogacestat for Ovarian Cancer

Not currently recruiting at 51 trial locations

Overseen By SpringWorks Clinical

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: SpringWorks Therapeutics, Inc.

Must not be taking: Bevacizumab, Monoclonal antibodies

Disqualifiers: Bowel obstruction, Cardiac event, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called nirogacestat for ovarian granulosa cell tumors, a specific type of ovarian cancer. Researchers believe nirogacestat slows the growth and activity of these tumors. The trial is open to individuals with a confirmed diagnosis of this cancer type who have relapsed after previous treatments that cannot be addressed with surgery or radiation. Participants will receive nirogacestat to evaluate its effectiveness in treating their condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain treatments for ovarian granulosa cell tumors, such as hormonal therapy, chemotherapy, immunotherapy, targeted therapy, or any investigational treatment, at least 28 days before starting the study treatment.

Is there any evidence suggesting that nirogacestat is likely to be safe for humans?

Research has shown that nirogacestat has been tested in people for other conditions, generally resulting in manageable side effects. While some side effects occurred, they were not severe for most individuals. For instance, one study found that nirogacestat was linked to ovarian harm in about 75% of women, but this did not necessarily indicate danger. The treatment's effects were monitored and managed over time.

Additionally, nirogacestat has been studied for desmoid tumors, where it demonstrated consistent safety over longer periods. This provides some reassurance about its safety, although it might differ in ovarian granulosa cell tumors. It is important to note that this trial is in Phase 2, which remains early in testing for safety and effectiveness in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Unlike the standard treatments for ovarian cancer, which often include chemotherapy, surgery, and targeted therapies like PARP inhibitors, nirogacestat offers a unique approach by targeting the Notch signaling pathway. Researchers are excited about nirogacestat because this pathway plays a crucial role in cell differentiation and proliferation, which is often dysregulated in cancers. By focusing on this novel mechanism of action, nirogacestat has the potential to inhibit tumor growth more effectively and with potentially fewer side effects compared to traditional chemotherapy. This innovative targeting gives hope for improved outcomes for patients who may not respond well to existing treatments.

What evidence suggests that nirogacestat might be an effective treatment for ovarian granulosa cell tumors?

Research has shown that nirogacestat may help treat certain tumors. In earlier studies on desmoid tumors, nirogacestat helped patients live longer without tumor progression and reduced tumor size in many cases. Specifically, one study found that 45.7% of patients experienced tumor shrinkage, with some even achieving complete tumor disappearance. Nirogacestat blocks an enzyme called gamma secretase, which is believed to aid tumor growth. This trial will evaluate nirogacestat for ovarian granulosa cell tumors, aiming to possibly slow their growth and activity. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with recurrent ovarian granulosa cell tumors who've had at least one systemic therapy and can't have surgery or radiation. They must have measurable tumor growth, no major heart events or abnormal QT intervals recently, and not be on certain treatments like monoclonal antibodies within the last 28 days.

Inclusion Criteria

My ovarian cancer is a confirmed adult-type granulosa cell tumor.

My cancer returned after treatment and can't be removed by surgery or treated with radiation, but it can be measured.

My blood, kidney, and liver tests are within normal ranges.

Exclusion Criteria

I have a bowel blockage or a condition that affects how my body absorbs medication.

I have a history of liver disease or liver/bile duct issues.

I have not had treatments like chemotherapy for my ovarian germ cell tumor in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label nirogacestat until disease progression or unacceptable toxicity

Up to 2.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Nirogacestat

Trial Overview The trial is testing Nirogacestat, a drug thought to slow down the growth of ovarian granulosa cell tumors. It's a phase 2 study which means it focuses on the effectiveness of this treatment for patients who meet specific criteria.

How Is the Trial Designed?

Group I: Nirogacestat Open-Label Experimental Treatment 1 Intervention

All participants will receive open-label nirogacestat

Who Is Running the Clinical Trial?

SpringWorks Therapeutics, Inc.

Lead Sponsor

Trials

14

Recruited

900+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00582

Efficacy and Safety of Long-Term Continuous Nirogacestat ... The ORR with up to 4 years of nirogacestat treatment was 45.7% (32 of 70), with three additional partial and three additional complete responses ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2210140

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning ...

3. targetedonc.com targetedonc.com/view/nirogacestat-yields-clinical-improvement-in-patients-with-desmoid-tumors

Nirogacestat Yields Clinical Improvement in Patients With ... Nirogacestat significantly improved progression-free survival and objective response rates in desmoid tumor patients compared to placebo. · Long- ...

4. onclive.com onclive.com/view/long-term-defi-data-confirm-durable-efficacy-and-consistent-safety-of-nirogacestat-in-desmoid-tumors

Long-Term DeFi Data Confirm Durable Efficacy and ... Nirogacestat demonstrated sustained efficacy and safety in treating progressing desmoid tumors, with improved objective response rates over time ...

5. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(23)00990-3/fulltext

A phase two trial of nirogacestat, a gamma-secretase ... Secondary endpoints include estimated 6-month progression-free survival and 2-year overall survival, change from baseline in the Functional Assessment of Cancer ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38703010/

Onset and resolution of ovarian toxicity with nirogacestat ... Results: Of 92 randomized females, 73 in the safety population were FORP (n = 36 nirogacestat, n = 37 placebo). OT was identified in 75% (27 of ...

7. ir.springworkstx.com ir.springworkstx.com/news-releases/news-release-details/springworks-therapeutics-announces-publication-long-term/

Press Release Details SpringWorks Therapeutics Announces Publication of Long-Term Efficacy and Safety Data from the Phase 3 DeFi Trial of OGSIVEO® (nirogacestat) in ...