Belzutifan for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Panagiotis Konstantinopoulos, MD, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inducers, Herbal supplements

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: Up to 3 years

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Belzutifan (also known as Welireg or MK-6482), a new drug targeting certain gynecologic cancers, such as ovarian cancer and those related to endometriosis. The main goal is to determine if Belzutifan is effective and safe for individuals with these specific cancers. The trial seeks participants diagnosed with clear cell carcinoma of the ovary or similar conditions who have already undergone at least one platinum-based chemotherapy treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use herbal supplements or certain medications that interact with the study drug. It's best to discuss your current medications with the study team to see if any changes are needed.

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

A previous study tested Belzutifan in patients with advanced cancers. The study found that Belzutifan was generally well-tolerated, with most participants experiencing mild to moderate side effects such as tiredness, nausea, and low red blood cell counts. Serious side effects were less common.

Belzutifan blocks a protein called Hypoxia-Inducible Factor-2 alpha (HIF-2a), which can promote tumor growth. By blocking this protein, Belzutifan aims to slow tumor growth.

Currently, Belzutifan is in a Phase 2 trial for ovarian cancer, having already passed earlier safety tests. These tests help ensure the drug is safe enough for broader use. While Belzutifan shows promise, individual reactions may vary. Discuss potential risks and benefits with a doctor.

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

Belzutifan is unique because it targets the hypoxia-inducible factor (HIF) pathway, which plays a key role in how cancer cells adapt to low oxygen environments—a common trait in tumors. Unlike standard chemotherapy or radiation treatments for ovarian cancer, which target rapidly dividing cells in a more general sense, Belzutifan specifically interrupts this pathway, potentially leading to more targeted and effective treatment. Researchers are excited about Belzutifan because its novel mechanism could offer new hope for patients whose cancer is resistant to existing therapies.

What evidence suggests that Belzutifan might be an effective treatment for ovarian cancer?

Studies have shown that Belzutifan effectively blocks a protein called HIF-2a, which aids cancer cell survival in low-oxygen conditions. By blocking this protein, Belzutifan may slow or stop the growth of certain cancer cells. Previous research on Belzutifan for other tumors has shown promising results, with some patients experiencing tumor shrinkage or disease stabilization. Although limited data exists specifically for ovarian cancer, the drug's mechanism suggests potential benefits for gynecologic cancers, including ovarian cancer. Early findings in other cancer types provide hope for similar effectiveness here. Participants in this trial will receive Belzutifan to evaluate its effectiveness for ovarian cancer.

Who Is on the Research Team?

Panagiotis Konstantinopoulos, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent clear cell ovarian carcinoma, a type of ovarian cancer. Participants should have experienced the return of their cancer after treatment. Specific eligibility criteria are not provided, but typically include factors like age, overall health status, and previous treatments.

Inclusion Criteria

My ovarian cancer is mainly clear cell type.

I can take pills by mouth.

I have another cancer that won't affect this study's treatment.

Exclusion Criteria

I have a digestive condition that affects how medicines work in my body.

I have a serious heart condition.

I have previously used Belzutifan or another HIF-2a inhibitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Belzutifan daily for 28-day cycles with in-clinic visits and imaging every 2 cycles

Up to 3 years

In-clinic visits on Day 1 and Day 15 of each cycle, imaging every 2 cycles

End of Treatment

End of treatment visit with ECG, blood tests, and imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Belzutifan

Trial Overview The study is testing Belzutifan's effectiveness and safety in treating ovarian cancer. Belzutifan is an inhibitor targeting Hypoxia-Inducible Factor-2 alpha (HIF-2a), which may play a role in tumor growth and survival.

How Is the Trial Designed?

Group I: Belzutifan Experimental Treatment 1 Intervention

15 participants will be enrolled for Stage 1 and will complete: * Baseline in-clinic visit * Imaging every 2 cycles * ECG on Day 1 of each cycle * Cycle 1 through End of Treatment: * Day 1 through 28 of 28 day cycle: Predetermined dose of Belzutifan 1x daily. * Day 15 of 28 day cycle: in-clinic visit * Cycle 2 Day 15 of 28 day cycle: in-clinic visit * End of treatment visit with ECG, blood tests, and imaging. * 30 Day post-treatment visit * Long-term follow up: every 6 months for 3 years * If 3 or more participants have objective response OR 2 or more participants are progression-free at 6 months, the study will enroll an additional 14 participants for Stage 2. Otherwise, enrollment will stop if there are less than 3 participants with objective response AND less than 2 participants are progression-free at 6 months.

Belzutifan is already approved in United States for the following indications:

Approved in United States as Welireg for:

• Advanced renal cell carcinoma (RCC) following a PD-1 or PD-L1 inhibitor and a VEGF TKI
• Von Hippel-Lindau disease-associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In the SOLO2 trial, patients with platinum-sensitive relapsed ovarian cancer who received maintenance olaparib had a significantly shorter time to second progression (TTSP) after disease progression compared to those who received a placebo, indicating reduced efficacy of subsequent chemotherapy after olaparib treatment.

Specifically, patients treated with platinum-based chemotherapy after olaparib had a TTSP of only 7.0 months compared to 14.3 months for those who had not received olaparib, suggesting that prior treatment with PARP inhibitors may diminish the effectiveness of later platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial. Frenel, JS., Kim, JW., Aryal, N., et al.[2022]

In a phase II trial involving 12 women with recurrent ovarian cancer, vandetanib at a dose of 300 mg daily showed no significant clinical benefit, as there was a lack of response or disease stabilization beyond 6 months.

While vandetanib effectively reduced phosphorylation of the epidermal growth factor receptor (EGFR) in tumor biopsies, it did not consistently affect vascular endothelial growth factor (VEGF) receptor-2 or significantly change plasma VEGF levels, indicating limited efficacy in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2. Annunziata, CM., Walker, AJ., Minasian, L., et al.[2022]

In the gBRCAm expansion cohort, the combination of olaparib and durvalumab showed a high objective response rate of 92.2%, indicating strong efficacy in treating platinum-sensitive relapsed ovarian cancer.

The combination of olaparib, durvalumab, and bevacizumab in non-gBRCAm patients also demonstrated promising clinical activity, with a disease control rate of 74.2%, while safety profiles remained consistent with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study. Drew, Y., Kim, JW., Penson, RT., et al.[2023]

Olaparib (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.

In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. Vanderstichele, A., Loverix, L., Busschaert, P., et al.[2022]

Angiogenesis inhibitors significantly improve progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with recurrent ovarian cancer, based on a review of 13 studies involving 3953 patients.

However, these treatments are associated with a higher risk of severe adverse events (grade ≥ 3), indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of angiogenesis inhibitors for recurrent ovarian cancer: a meta‑analysis. Zhang, C., Zhao, W.[2022]

Citations