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

Trial Summary

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.

How is the drug Belzutifan unique for treating ovarian cancer?

Belzutifan is unique because it targets a specific pathway involved in cancer cell survival by inhibiting HIF-2α (a protein that helps cancer cells survive in low oxygen conditions), which is different from other treatments like olaparib that target DNA repair mechanisms. This novel approach may offer a new option for patients with ovarian cancer, especially those who do not respond to existing therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this research study is to see if the study drug Belzutifan is effective and safe for participants with ovarian cancer. The name of the study drug involved in this study is: - Belzutifan (a type of Hypoxia-Inducible Factor-2 alpha (HIF-2a) inhibitor)

Research Team

Panagiotis Konstantinopoulos, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. England 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]

4. United States 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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