Phase II Trial of Single Agent Belzutifan or Pembrolizumab Versus Combination as Neoadjuvant Therapy in Clear Cell Renal Cell Carcinoma (BLAZE)

NCT07187778 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2024-1884NCI-2025-06635
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if belzutifan alone, pembrolizumab alone, or belzutifan and pembrolizumab in combination given before a total or partial nephrectomy (surgery to remove all or part of a kidney) can help to control locally advanced ccRCC.

Conditions

Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 1. Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (3)

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

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: Belzutifan

Mono-B: Phase II Mono Neoadjuvant Treatment with Belzutifan (PO/QD)

EXPERIMENTAL

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

Drug: Belzutifan

Mono-P: Phase II Mono Neoadjuvant Treatment with Pembrolizumab (IV Q3W)

EXPERIMENTAL

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

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Oral administration

Also known as: Keytruda

Combo-B+P: Phase II Combo Neoadjuvant Treatment with Belzutifan (PO/QD) and Pembrolizumab (IV Q3W); Mono-P: Phase II Mono Neoadjuvant Treatment with Pembrolizumab (IV Q3W)

Belzutifan DRUG

Oral administration

Also known as: Welireg

Combo-B+P: Phase II Combo Neoadjuvant Treatment with Belzutifan (PO/QD) and Pembrolizumab (IV Q3W); Mono-B: Phase II Mono Neoadjuvant Treatment with Belzutifan (PO/QD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy proven clear cell renal cell carcinoma (ccRCC).
• a. Extra tissue should be submitted if available for correlative analysis. Formalin-fixed paraffinembedded (FFPE) tissue blocks are preferred to slides. Details pertaining to tumor tissue submission can be found in the Lab Procedures Manual.
• Has intermediate-high risk, high risk, or M1 ccRCC as defined by the following pathological tumor-node metastasis and tumor grading:
• Intermediate-high risk ccRCC\*
• pT2 (by radiographic/size criteria), Grade 4 or with sarcomatoid/rhabdoid features (on biopsy), N0, M0
• pT3 (presence of tumor thrombus, perinephric and/or sinus fat invastion by imaging), any grade, N0, M0 High-risk ccRCC\*
• pT4, any g.rade, N0, M0
• pT, any stage, any grade, N+, M0 M1 RCC participants who present with the primary kidney tumor, but also solid, isolated, soft tissue metastases that are planned to be completely resected at the time of nephrectomy are eligible (e.g. metastasis to ipsilateral adrenal gland).
• NOTE: Fuhrman Tumor Grade and/or WHO/ISUP Tumor Grade are required for all subjects entering the study.
• Evaluated by urology and approved as candidates for nephrectomy.
• Age ≥18 years and consent to participation.
• Performance status of 0-1 per Zubrod/Eastern Cooperative Oncology Group \[ECOG\] scale.
• Absence of distant metastases on imaging of chest, abdomen and pelvis within 42 days of enrollment (by CT, MRI, or PET imaging). Brain imaging is not required unless clinical suspicion per the treating provider.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Screening laboratory criteria include the following: a. ANC ≥1000, PLT ≥ 75, Hgb ≥9 (transfusion allowed if Hgb \< 1.5 or = to upper limit of normal

You may not qualify if:

• Has any of the following:
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• A pulse oximeter reading \<92% at rest, or
• Requires intermittent supplemental oxygen, or
• Requires chronic supplemental oxygen
• Patients who have had chemotherapy or radiotherapy for RCC prior to study.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to belzutifan, pembrolizumab, or other agents used in study.
• Prior systemic therapy with anti-PD1, PD-L1, PD-L2, or CTLA-4 or received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant EPO) ≤28 days prior to the first dose of study intervention.
• Diagnosis of immunodeficiency, active autoimmune disease (per Investigator's discretion), history of pneumonitis, active infection, or known additional malignancy other than RCC.
• Has a known history of HIV infection. Note: Testing for HIV at screening is only required if mandated by local health authority.
• Has a known history of HBV (defined as HBsAg reactive) or known active HCV (defined as HCV RNA \[qualitative\] is detected) infection.
• Note: Testing for HBV and HCV is only required if mandated by local health authority.
• Patients who cannot fulfill study requirements for any reason.
• Pregnant or breastfeeding women are excluded from this study because pembrolizumab is a Class-D agent with the potential for teratogenic or abortifacient effects and belzutifan has shown embryofetal toxicity in nonclinical studies

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pembrolizumab; belzutifan

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Eric Jonasch, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Jonasch, MD

CONTACT

(713) 563-7232; ejonasch@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2025
• First Posted: September 23, 2025
• Study Start: December 19, 2025
• Primary Completion (Estimated): July 19, 2027
• Study Completion (Estimated): July 19, 2029
• Last Updated: January 5, 2026

Record last verified: 2026-01

Locations

US (1)