Belzutifan + Pembrolizumab for Kidney Cancer

Recruiting at 298 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Steroids, Immunosuppressive drugs

Disqualifiers: Cardiovascular disease, Brain metastases, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 9

Duration: 54 weeks

1800 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment in patients who have had kidney cancer surgery. The goal is to see if this treatment can prevent the cancer from coming back. One part of the treatment stops cancer cells from surviving in low oxygen, and the other part helps the immune system attack the cancer. This approach has shown improved survival rates in treating advanced kidney cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive drugs, you may need to discuss this with the trial team, as these are mentioned in the exclusion criteria.

What data supports the effectiveness of the drug Belzutifan + Pembrolizumab for kidney cancer?

Research shows that Belzutifan combined with another drug, cabozantinib, has been effective in treating advanced kidney cancer. Additionally, Pembrolizumab, when used with axitinib, has improved survival rates in patients with metastatic kidney cancer. ^{1 2 3 4 5}

Is the combination of Belzutifan and Pembrolizumab safe for humans?

Pembrolizumab has shown acceptable safety in patients with urothelial carcinoma, and Belzutifan has been studied for safety in combination with other drugs for renal cell carcinoma. While specific safety data for the combination of Belzutifan and Pembrolizumab is not provided, both drugs have been evaluated for safety in other contexts. ^{1 2 6 7 8}

What makes the drug combination of Belzutifan and Pembrolizumab unique for kidney cancer?

The combination of Belzutifan and Pembrolizumab is unique for kidney cancer because it pairs an innovative drug, Belzutifan, which targets a specific pathway involved in cancer growth, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the effectiveness of treatment by using two different mechanisms to combat the cancer. ^{1 2 9 10 11}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults who've had kidney cancer surgery within the last 12 weeks. They should have a certain level of risk for their cancer returning but no current evidence of disease spread, and must be in good physical condition (ECOG 0-1). Participants need proper organ function and can't join if they've had major recent surgeries, severe heart issues, active infections or autoimmune diseases, other cancers within 3 years, or specific lung conditions.

Inclusion Criteria

I will continue using birth control for at least 7 days after my last dose.

I am fully active or restricted in physically strenuous activity but can do light work.

My organs are functioning well.

Exclusion Criteria

I have received treatment for kidney cancer before.

I need extra oxygen sometimes or all the time.

My cancer has spread to my brain or bones.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belzutifan or placebo orally once daily for up to approximately 54 weeks, plus pembrolizumab via IV infusion every 6 weeks for up to 9 administrations

54 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term Follow-up

Participants are monitored for disease-free survival and overall survival

Up to approximately 89 months

Treatment Details

Interventions

• Belzutifan
• Pembrolizumab

Trial Overview The study tests if taking belzutifan pills with pembrolizumab injections works better than placebo pills with pembrolizumab for preventing kidney cancer from coming back after surgery. The main goal is to see which combination leads to longer periods without the disease returning.

Participant Groups

Group I: Placebo + Pembrolizumab Experimental Treatment 2 Interventions

Participants receive placebo orally QD for up to approximately 54 weeks PLUS pembrolizumab 400 mg via IV infusion once Q6W for up to 9 administrations (up to approximately 54 weeks).

Group II: Belzutifan + Pembrolizumab Experimental Treatment 2 Interventions

Participants receive belzutifan 120 mg orally once daily (QD) for up to approximately 54 weeks PLUS pembrolizumab 400 mg via intravenous (IV) infusion once every 6 weeks (Q6W) for up to 9 administrations (up to approximately 54 weeks).

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?

Merck Sharp & Dohme LLC

Lead 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

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 II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a subgroup analysis of 94 Japanese patients with metastatic renal cell carcinoma, the combination of pembrolizumab and axitinib showed improved overall survival and progression-free survival compared to sunitinib, consistent with results from the larger global study.

The safety profile was also favorable, with fewer grade ≥3 treatment-related adverse events in the pembrolizumab-axitinib group (70%) compared to sunitinib (78%), and no deaths from treatment-related adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. Tamada, S., Kondoh, C., Matsubara, N., et al.[2022]

In a study of 52 treatment-naïve patients with advanced renal cell carcinoma receiving axitinib and pembrolizumab, higher baseline levels of immune-related biomarkers like CD8 and CXCL10 were associated with longer progression-free survival and better response rates.

The presence of IL6 at baseline was linked to shorter progression-free survival, suggesting that certain biomarkers could help predict treatment outcomes and warrant further investigation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma. Martini, JF., Plimack, ER., Choueiri, TK., et al.[2023]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[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]

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]

Atezolizumab, a PD-L1 antibody, showed a manageable safety profile in 70 patients with metastatic renal cell carcinoma (RCC), with only 17% experiencing grade 3 treatment-related adverse events and no severe (grade 4 or 5) events reported.

The treatment demonstrated promising clinical activity, with a median overall survival of 28.9 months and an objective response rate of 15%, particularly higher in patients with specific tumor characteristics, suggesting potential biomarkers for predicting response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. McDermott, DF., Sosman, JA., Sznol, M., et al.[2022]

This study presents the first known case of a patient with metastatic melanoma who was successfully treated with pembrolizumab while undergoing hemodialysis, highlighting its potential efficacy in patients with end-stage renal disease.

Pembrolizumab, an FDA-approved monoclonal antibody for metastatic melanoma and non-small cell lung cancer, shows promise for use in patients with renal complications, although specific dosing guidelines for such patients are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. Chang, R., Shirai, K.[2019]

References

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

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

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. [2022]

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

Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma. [2023]

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

Cost-effectiveness of Adjuvant Pembrolizumab After Nephrectomy for High-risk Renal Cell Carcinoma: Insights for Patient Selection From a Markov Model. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. [2023]

7. 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]

8. 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]

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

Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Pembrolizumab outperforms tyrosine kinase inhibitors as adjuvant treatment in patients with high-risk renal cell carcinoma after nephrectomy. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. [2019]