Belzutifan + Cabozantinib for Kidney Cancer

Recruiting at 9 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Peloton Therapeutics, Inc.

Must not be taking: Anticoagulants, HIF2α inhibitors

Disqualifiers: Brain metastases, Hypertension, Cardiovascular, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 2 years

118 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anticoagulant therapy, you may not be eligible to participate.

What data supports the effectiveness of the drug combination Belzutifan and Cabozantinib for kidney cancer?

Research shows that the combination of Belzutifan and Cabozantinib has antitumor activity in patients with advanced kidney cancer who have already received immunotherapy. Cabozantinib alone has also shown effectiveness in kidney cancer, with a significant response rate and ability to stabilize the disease. ^{1 2 3 4 5}

What safety data exists for the combination of Belzutifan and Cabozantinib in treating kidney cancer?

The combination of Belzutifan and Cabozantinib has been studied for safety in patients with advanced kidney cancer. Common side effects include fatigue and diarrhea, which are manageable with medical intervention or dosage adjustments. ^{1 2 3 5 6}

How is the drug combination of Belzutifan and Cabozantinib unique for treating kidney cancer?

The combination of Belzutifan and Cabozantinib is unique because it targets kidney cancer in patients who have already been treated with immunotherapy. Belzutifan works by inhibiting HIF-2α, which is involved in cancer growth, while Cabozantinib blocks multiple pathways that help tumors grow, potentially offering more effective treatment than using either drug alone. ^{1 2 3 5 7}

What is the purpose of this trial?

This is an open-label Phase 2 study which will evaluate the efficacy and safety of belzutifan in combination with cabozantinib in participants with advanced ccRCC. Belzutifan and cabozantinib will be administered orally once daily.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced clear cell renal cell carcinoma (ccRCC). Participants should have measurable tumors, good performance status, and proper organ function. Some can't join if they've had certain treatments for ccRCC or major surgery recently, uncontrolled hypertension, active infections needing treatment, or are in another clinical trial.

Inclusion Criteria

Your AST and ALT levels in your blood are not more than 3 times the normal limit.

My kidney cancer is advanced or has spread and is mainly clear cell type.

You have at least one tumor that can be measured according to specific guidelines.

Exclusion Criteria

Is participating in another therapeutic clinical trial

I do not have any major health or mental conditions that could affect my trial participation.

I still have side effects from previous cancer treatments that haven't gone away.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belzutifan and cabozantinib orally once daily

Up to approximately 2 years

Regular visits for monitoring and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Belzutifan
• Cabozantinib

Trial Overview The study tests the effectiveness and safety of combining two oral drugs: Belzutifan and Cabozantinib. It's an open-label Phase 2 study where all participants know which treatment they're getting and take the medications daily to treat advanced kidney cancer.

Participant Groups

Group I: Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1) Experimental Treatment 2 Interventions

Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.

Group II: Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2) Experimental Treatment 2 Interventions

Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.

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?

Peloton Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

460+

Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Lead Sponsor

Trials

8

Recruited

460+

Findings from Research

The combination of belzutifan and cabozantinib shows promising antitumor activity in patients with advanced clear cell renal cell carcinoma who have already undergone previous treatments.

This study highlights the potential of this drug combination as a new therapeutic option for patients with this challenging form of kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan Plus Cabozantinib Is Effective in Immunotherapy-Treated Renal Cell Carcinoma. [2023]

In a phase 2 study involving 52 patients with advanced clear cell renal cell carcinoma who had previously received immunotherapy, the combination of belzutifan and cabozantinib showed promising antitumour activity, with 30.8% of patients achieving a confirmed objective response, including one complete response.

The treatment was associated with manageable safety concerns, primarily hypertension (27% of patients), and serious treatment-related adverse events occurred in 29% of patients, indicating that while the combination therapy is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. Choueiri, TK., McDermott, DF., Merchan, J., et al.[2023]

Cabozantinib has shown significant efficacy in treating advanced kidney cancer, with a 28% objective response rate and a median progression-free survival of 14.7 months based on a phase II trial involving patients with renal cancer.

The drug also demonstrated notable effectiveness in managing bone metastases, which is crucial for improving quality of life in patients, and further studies are planned to compare its effectiveness against standard VEGF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib as a novel therapy for renal cell carcinoma. Vaishampayan, U.[2022]

Cabozantinib shows promising anti-tumor activity in patients with metastatic clear cell renal cell carcinoma (RCC), with a partial response observed in 28% of the 25 heavily pretreated participants.

The treatment demonstrated a median progression-free survival of 12.9 months and a median overall survival of 15.0 months, with a safety profile consistent with other similar therapies, indicating its potential as a viable option for advanced RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Choueiri, TK., Pal, SK., McDermott, DF., et al.[2021]

Belzutifan, a first-in-class HIF-2α inhibitor, shows promising antitumor activity in patients with clear cell renal cell carcinoma (RCC) who have previously been treated, indicating its potential as a new treatment option.

The ongoing phase III study is comparing the combination of belzutifan with lenvatinib against cabozantinib in patients with advanced RCC who have progressed after anti-PD-1/PD-L1 therapy, addressing a significant need for effective treatments in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. Motzer, RJ., Schmidinger, M., Eto, M., et al.[2023]

Cabozantinib (Cabometyx®) is now approved as a first-line treatment for advanced renal cell carcinoma (RCC) in treatment-naïve adults, expanding its use beyond patients who have already received VEGF-targeted therapy.

In a phase 2 trial, cabozantinib significantly improved median progression-free survival and objective response rates compared to the standard treatment sunitinib, while its side effects are manageable, similar to other tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use. Lyseng-Williamson, KA.[2020]

Belzutifan (Welireg™) is an oral medication that inhibits HIF-2α and has been approved in the USA for treating patients with von Hippel-Lindau (VHL) disease who have associated renal cell carcinoma (RCC) and other tumors, marking a significant advancement in targeted cancer therapy.

Clinical studies are ongoing to evaluate the efficacy of belzutifan in treating other solid tumors, including clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine tumors (pNET), indicating its potential for broader applications in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan: First Approval. Deeks, ED.[2022]

References

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

Belzutifan Plus Cabozantinib Is Effective in Immunotherapy-Treated Renal Cell Carcinoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. [2023]

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

Cabozantinib as a novel therapy for renal cell carcinoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. [2021]

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

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Belzutifan: First Approval. [2022]