What side effects are associated with this type of intervention?

Common treatments for Renal Cell Carcinoma (RCC) include tyrosine kinase inhibitors (TKIs) like sunitinib, pazopanib, and axitinib, as well as immune checkpoint inhibitors such as nivolumab and ipilimumab. The side effects of TKIs often include hypertension, diarrhea, fatigue, hand-foot syndrome, and liver toxicity. Immune checkpoint inhibitors can cause immune-related adverse events such as colitis, hepatitis, pneumonitis, and endocrinopathies. Belzutifan, a HIF-2α inhibitor, is being studied for its safety and tolerability, and its side effect profile may include similar adverse events.

What prior FDA approvals exist?

The FDA has approved several treatments for Renal Cell Carcinoma (RCC), including tyrosine kinase inhibitors (TKIs) like sunitinib and pazopanib, which target vascular endothelial growth factor receptors (VEGFR). Additionally, immune checkpoint inhibitors such as nivolumab and pembrolizumab, which target PD-1, have been approved for RCC. Belzutifan, a HIF-2α inhibitor, is being studied for its efficacy in RCC, representing a novel approach by targeting hypoxia-inducible factors. These treatments aim to inhibit tumor growth and improve survival outcomes in patients with advanced RCC.

What other types of research exist?

Promising novel alternatives to Belzutifan for RCC patients include: 1) Lenvatinib plus Pembrolizumab, which has shown improved progression-free survival and overall response rates in clinical trials. 2) Cabozantinib, which has demonstrated efficacy in both treatment-naïve and previously treated RCC patients. 3) Atezolizumab plus Bevacizumab, which has shown potential benefits in specific patient subgroups with advanced RCC. These alternatives offer different mechanisms of action and have shown promising results in recent studies.

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HIF-2alpha Inhibitor

Belzutifan for Kidney Cancer

Phase 1

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has a histologically-confirmed diagnosis of unresectable, locally advanced/metastatic RCC with clear cell component (with or without sarcomatoid features) (may include participants with a diagnosis of von Hippel-Lindau [VHL] associated ccRCC)

Has experienced disease progression on or after having received at least one previous systemic treatment for advanced ccRCC

Must not have

Has received prior treatment with belzutifan

Has a history or current evidence of a gastrointestinal (GI) condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to ~49.5 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing belzutifan, a medication for patients with advanced kidney cancer that hasn't responded to previous treatments. The drug works by blocking a protein that cancer cells need to grow. Researchers aim to find out if it is safe and effective for these patients. Belzutifan has received FDA approval for treating von Hippel-Lindau-associated renal cell carcinoma and has shown significant efficacy in related tumors.

Who is the study for?

This trial is for adults with advanced clear cell renal cell carcinoma who've had disease progression after at least one systemic treatment. They must have good organ function, agree to use contraception, and not be pregnant or breastfeeding. Exclusions include those with hypoxia, other active cancers within 3 years (except certain skin/in situ cancers), HIV/hepatitis infections, prior belzutifan treatment, recent anticancer antibodies or radiotherapy, major surgery within 3 weeks, brain metastasis, severe heart/liver conditions or infections.

What is being tested?

The study tests the safety and effects of different doses of Belzutifan in patients with advanced kidney cancer as a second-line treatment. It aims to understand how the body handles the drug (pharmacokinetics) and its tolerability when given after another therapy has failed.

What are the potential side effects?

While specific side effects for Belzutifan are not listed here, similar drugs may cause fatigue, nausea, liver issues like increased enzymes indicating damage or inflammation; anemia; decreased appetite; changes in taste; coughing; shortness of breath.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney cancer cannot be surgically removed and has spread.

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My kidney cancer has worsened after at least one treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with belzutifan before.

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I have a history of GI issues or liver problems.

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My liver is not working well.

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I need extra oxygen sometimes or all the time.

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I am currently being treated for an active infection.

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I have had or currently have cancer spread to my brain or its coverings.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to ~49.5 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to ~49.5 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to ~49.5 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants Who Discontinue Study Treatment Due to an AE

Percentage of Participants Who Experience at Least One Adverse Event (AE)

Percentage of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)

+1 more

Secondary study objectives

Area Under the Plasma Concentration Time Curve (AUC) of Belzutifan

Maximum Observed Plasma Concentration (Cmax) of Belzutifan

Minimum Observed Plasma Concentration (Cmin) of Belzutifan

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Belzutifan 200 mg TIDExperimental Treatment1 Intervention

Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation.

Group II: Belzutifan 160 mg TIDExperimental Treatment1 Intervention

Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation.

Group III: Belzutifan 160 mg BIDExperimental Treatment1 Intervention

Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation.

Group IV: Belzutifan 120 mg QDExperimental Treatment1 Intervention

Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease or discontinuation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Belzutifan

2018

Completed Phase 1

~50

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Renal Cell Carcinoma (RCC) include tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and HIF-2α inhibitors like Belzutifan. TKIs, such as sunitinib and pazopanib, block signals that promote tumor growth and angiogenesis by inhibiting vascular endothelial growth factor (VEGF) pathways. Immune checkpoint inhibitors, like nivolumab, enhance the immune system's ability to recognize and destroy cancer cells by targeting proteins such as PD-1/PD-L1. HIF-2α inhibitors, including Belzutifan, specifically target the hypoxia-inducible factor pathway, which is crucial in RCC due to its role in promoting tumor survival and growth under low oxygen conditions. Understanding these mechanisms is vital for RCC patients as it helps tailor treatments that can effectively target the specific pathways driving their cancer, potentially improving outcomes and minimizing side effects.

The future of tyrosine kinase inhibitors: single agent or combination?