Belzutifan + Pembrolizumab for Kidney Cancer

Not currently recruiting at 379 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for kidney cancer to determine if it can help people remain cancer-free longer after surgery. Participants will receive either the new treatment, belzutifan (also known as Welireg, an experimental treatment), with the existing drug, pembrolizumab (also known as KEYTRUDA, an immunotherapy drug), or a placebo with pembrolizumab. The trial targets individuals who have recently undergone surgery to remove clear cell renal cell carcinoma (a type of kidney cancer) and may still be at risk of recurrence. Those who have had a complete removal of their kidney tumor and any isolated metastatic lesions (spread of cancer) and have not received prior systemic treatment for this cancer may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of belzutifan and pembrolizumab is generally safe. In earlier studies, patients taking these drugs together experienced manageable side effects, with no surprising or severe reactions.

Pembrolizumab is already approved for treating other types of cancer, confirming its safety. Belzutifan is being tested in different combinations and has demonstrated a good balance of benefits and risks in other studies. Overall, patients handle the combination well, with side effects similar to those of other cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about belzutifan plus pembrolizumab for kidney cancer because this combination targets the disease in a new way. Unlike traditional treatments such as tyrosine kinase inhibitors or mTOR inhibitors, belzutifan works by inhibiting HIF-2α, a protein that plays a crucial role in how cancer cells survive and grow under low-oxygen conditions. When combined with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, this treatment offers a potentially powerful one-two punch against kidney cancer. The innovative approach of targeting both the tumor environment and the immune system is what sets these treatments apart.

What evidence suggests that belzutifan plus pembrolizumab could be an effective treatment for kidney cancer?

Research has shown that using belzutifan with pembrolizumab may improve outcomes for patients with clear cell renal cell carcinoma (ccRCC). In this trial, one group of participants will receive the combination of belzutifan and pembrolizumab. Studies have found that this combination significantly increases the time patients remain cancer-free after surgery compared to using pembrolizumab alone. Pembrolizumab helps the immune system fight cancer, while belzutifan stops a protein that aids cancer cell growth. Together, these treatments offer a promising way to prevent cancer recurrence after tumor removal. Another group in this trial will receive a placebo with pembrolizumab to compare outcomes. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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 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]

Citations

1. merck.com merck.com/news/merck-announces-keytruda-pembrolizumab-plus-welireg-belzutifan-met-primary-endpoint-of-disease-free-survival-dfs-in-certain-patients-with-clear-cell-renal-cell-carcinoma-rcc-follow/

Merck Announces KEYTRUDA® (pembrolizumab) Plus ... First combination regimen to demonstrate improvement in DFS compared to KEYTRUDA monotherapy for these patients in the adjuvant setting.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05239728

NCT05239728 | A Study of Belzutifan (MK-6482) Plus ... The purpose of this study is to assess the efficacy and safety of oral belzutifan (MK-6482) plus intravenous (IV) pembrolizumab (MK-3475) compared to placebo ...

3. merck.com merck.com/news/merck-and-eisai-announce-welireg-belzutifan-plus-lenvima-lenvatinib-met-primary-endpoint-of-progression-free-survival-pfs-in-certain-previously-treated-patients-with-advanced-renal-c/

Merck and Eisai Announce WELIREG® (belzutifan) Plus ... First treatment regimen to demonstrate a statistically significant improvement in PFS for patients whose disease progressed following anti-PD-1/L1 therapy ...

4. onclive.com onclive.com/view/belzutifan-based-combinations-meet-dfs-pfs-end-points-in-renal-cell-carcinoma

Belzutifan-Based Combinations Meet DFS, PFS End Points ... These results mark belzutifan plus lenvatinib as the first treatment regimen to signfiicantly improved PFS vs cabozantinib following anti-PD-1/ ...

5. targetedonc.com targetedonc.com/view/interim-efficacy-data-favor-belzutifan-lenvatinib-in-advanced-rcc

Interim Efficacy Data Favor Belzutifan/Lenvatinib in ... A new trial shows that the combination of belzutifan and lenvatinib improves progression-free survival in advanced renal cell carcinoma patients ...

6. biospace.com biospace.com/press-releases/merck-announces-keytruda-pembrolizumab-plus-welireg-belzutifan-met-primary-endpoint-of-disease-free-survival-dfs-in-certain-patients-with-clear-cell-renal-cell-carcinoma-rcc-following-nephrectomy

Merck Announces KEYTRUDA® (pembrolizumab) Plus ... Merck Announces KEYTRUDA® (pembrolizumab) Plus WELIREG® (belzutifan) Met Primary Endpoint of Disease-Free Survival (DFS) in Certain Patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11567780/

Belzutifan for Patients with Advanced Renal Cell Carcinoma Higher ORR and longer DoR, favorable safety results, and descriptive PRO data in the belzutifan arm also supported a favorable benefit-risk profile of ...