Belzutifan + Pembrolizumab for Renal Cell Carcinoma

Overseen By Eric Jonasch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-PD1, PD-L1, CTLA-4

Disqualifiers: Immunodeficiency, Autoimmune, HIV, 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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, belzutifan (a new potential drug) and pembrolizumab (an immunotherapy drug), to determine their effectiveness in controlling clear cell renal cell carcinoma (ccRCC), a type of kidney cancer, before kidney removal surgery. Researchers will evaluate each drug individually and in combination to identify the most effective approach. The trial suits individuals with locally advanced ccRCC who are candidates for kidney surgery and do not have distant metastases that cannot be surgically removed. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial requires that you stop taking strong or moderate inducers of CYP3A4 (a liver enzyme) for the duration of the study. If you are on any of these medications, you will need to discuss with your doctor about stopping them before joining the trial.

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

Research has shown that belzutifan and pembrolizumab, both used to treat kidney cancer, have specific safety profiles based on recent studies.

For belzutifan, research indicates it is generally well-tolerated. Some patients experienced mild anemia (low red blood cell levels), while a few had more serious anemia and low oxygen levels. Despite these effects, belzutifan is already approved for other conditions, suggesting confidence in its safety.

Pembrolizumab has been widely studied and used for various cancers. It is considered safe to manage, though some patients experience side effects related to the treatment. Studies suggest it is generally well-tolerated, but more serious side effects can occur.

When used together, belzutifan and pembrolizumab have shown good tolerability in patients with advanced kidney cancer. This suggests that using both drugs does not significantly increase the risk of serious side effects compared to using each drug alone. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for renal cell carcinoma because they bring a fresh approach to managing this cancer type. Belzutifan, one of the study drugs, targets a protein called HIF-2α, which plays a key role in tumor growth, offering a novel mechanism compared to standard treatments like tyrosine kinase inhibitors and immune checkpoint inhibitors. Pembrolizumab, an immune checkpoint inhibitor, is already used in cancer therapy, but its combination with Belzutifan could enhance its effectiveness by tackling the cancer from multiple angles. By combining these therapies, researchers hope to improve outcomes and offer new hope for patients with this challenging condition.

What evidence suggests that this trial's treatments could be effective for renal cell carcinoma?

This trial will evaluate different treatment options for renal cell carcinoma (RCC). Studies have shown that combining belzutifan and pembrolizumab can significantly extend the time patients with RCC live without disease progression. This combination has outperformed treatments like cabozantinib in trials. In this trial, some participants will receive the combination of belzutifan and pembrolizumab. Others will receive pembrolizumab alone, which has been shown to help patients live longer and remain disease-free after kidney removal. Another group will receive belzutifan by itself, which has also shown promise in controlling the disease and delaying its progression. Overall, each treatment option—whether used alone or together—has proven effective in managing RCC. ^{1 2 5 6 7}

Who Is on the Research Team?

Eric Jonasch, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with locally advanced clear cell renal cell carcinoma (ccRCC) who are candidates for kidney removal surgery. Specific eligibility details aren't provided, but typically participants must be adults in good general health and meet certain lab criteria.

Inclusion Criteria

Screening laboratory criteria including ANC, PLT, and Hgb levels

Ability to understand and willingness to sign a written informed consent document

I am 18 years or older and agree to participate.

Exclusion Criteria

History of allergic reactions to study compounds

My liver is not working well.

I am currently being treated for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive either belzutifan alone, pembrolizumab alone, or a combination of both as neoadjuvant therapy

12 weeks

Evaluations at baseline, 3 weeks, 6 weeks, 9 weeks, and 12 weeks

Surgery

Participants undergo total or partial nephrectomy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belzutifan
• Pembrolizumab

Trial Overview The BLAZE study is testing whether taking belzutifan alone, pembrolizumab alone, or both drugs together before kidney surgery can help control ccRCC better than current treatments.

How Is the Trial Designed?

Group I: Mono-P: Phase II Mono Neoadjuvant Treatment with Pembrolizumab (IV Q3W) Experimental Treatment 1 Intervention

Participants will undergo evaluations at baseline, 3 weeks, 6 weeks, 9 weeks, and 12 weeks after initiation of treatment

Group II: Mono-B: Phase II Mono Neoadjuvant Treatment with Belzutifan (PO/QD) Experimental Treatment 1 Intervention

Participants will undergo evaluations at baseline, 3 weeks, 6 weeks, 9 weeks, and 12 weeks after initiation of treatment

Group III: Combo-B+P: Phase II Combo Neoadjuvant Treatment with Belzutifan (PO/QD) and Pembrolizumab (IV Q3W) Experimental Treatment 2 Interventions

Participants will undergo evaluations at baseline, 3 weeks, 6 weeks, 9 weeks, and 12 weeks after initiation of treatment

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12509838/

59: Real-World efficacy and safety of belzutifan in sporadic ... The disease control rate was 64%. The median OS was 6.93 months (95% CI: 3.75-12.58). The median PFS was 3.09 months (95% CI 2.53-5.72). AEs of ...

2. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.70023

Belzutifan's role in the treatment landscape of clear cell ... The major efficacy outcome measures were progression-free survival (PFS) and OS. Significant improvement in PFS was demonstrated for belzutifan ...

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

Belzutifan-Based Combinations Meet DFS, PFS End ... LITESPARK-011 and LITESPARK-022 trials showed significant PFS and DFS improvements in RCC with belzutifan combinations, surpassing cabozantinib ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.549

Updated results from the phase 2 LITESPARK-003 study of ... Belzutifan plus cabozantinib showed durable antitumor activity in both frontline and subsequent-line treatment of patients with RCC and a safety profile ...

5. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-kidney-cancer/158330-asco-gu-2025-updated-results-from-the-phase-2-litespark-003-study-of-belzutifan-plus-cabozantinib-in-patients-with-advanced-clear-cell-renal-cell-carcinoma.html

Updated Results From the Phase 2 LITESPARK-003 Study ... In the initial analysis, the primary end point of objective response rate (ORR) was 57% in cohort 1 (n = 35) and 31% in cohort 2 (n = 52) after a median follow- ...

6. academic.oup.com academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyaf274/8249253?searchresult=1

The safety profile of belzutifan in renal tumors: real-world data ... While low-grade anemia remained common (82.8%), higher rates of grade ≥ 3 anemia and grade ≥ 3 hypoxia were observed in spRCC patients in LITESPARK-005,11 ...

7. urotoday.com urotoday.com/conference-highlights/suo-2024/suo-2024-kidney-cancer/156697-suo-2024-in-depth-characterization-of-the-safety-profile-of-belzutifan-monotherapy-in-patients-with-renal-cell-carcinoma-a-pooled-analysis-of-four-clinical-trials.html

In-Depth Characterization of the Safety Profile of Belzutifan ... Dr. Eric Jonasch presented a post hoc pooled analysis of four clinical trials evaluating the safety of belzutifan in patients with renal cell carcinoma (RCC).