NCT07516366

Testing the Safety and Feasibility of Immunotherapy Drugs, Botensilimab and Balstilimab, Before Surgery for Clear Cell Renal Cell Carcinoma, NEO RoBOT Trial

Pilot Phase II Trial Evaluating Safety and Feasibility of Neoadjuvant Botensilimab and Balstilimab in Clear Cell Renal Cell Carcinoma (NEO RoBOT)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests the effect of botensilimab and balstilimab before surgery (neoadjuvant) in treating patients with high-risk clear cell renal cell cancer that has not spread from where it first started to other areas of the body (non-metastatic). The current standard treatment for patients with non-metastatic clear cell renal cell cancer may include surgery to completely remove the tumor. This typically involves removing the kidney or part of the kidney (nephrectomy). Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant botensilimab and balstilimab may be safe, tolerable, and/or effective in treating patients with high-risk non-metastatic clear cell renal cell cancer before undergoing a nephrectomy.

Detailed description

PRIMARY OBJECTIVE: I. To investigate the safety and feasibility of neoadjuvant botensilimab and balstilimab in high-risk (T2a-T4Nany M0 or Tany N1M0) non-metastatic clear cell renal cell carcinoma via assessment of ability to undergo timely nephrectomy. SECONDARY OBJECTIVES: I. To investigate the safety of neoadjuvant botensilimab and balstilimab in high-risk (T2a-T4Nany M0 or Tany N1M0) non-metastatic clear cell renal cell carcinoma via assessment of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. II. To investigate the surgical morbidity of neoadjuvant botensilimab and balstilimab in high-risk (T2a-T4Nany M0 or Tany N1M0) non-metastatic clear cell renal cell carcinoma via assessment of Clavien-Dindo classification of surgical morbidity, respectively. III. To evaluate the objective response rate (ORR) of the primary tumor following neoadjuvant botensilimab and balstilimab per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, defined as complete response (CR) or partial response (PR), any time after starting treatment. IV. To evaluate the proportion of patients achieving a major pathologic response (defined as \< 10% of viable tumor in the tumor bed) and a partial pathologic response (defined as less than 50% of the viable tumor in tumor bed), through centralized pathology review. V. To evaluate disease-free survival (DFS), rates of distant metastasis and local recurrence following neoadjuvant botensilimab and balstilimab in high-risk clear cell renal cell carcinoma. EXPLORATORY OBJECTIVES: I. To investigate the relationship between tumor cell programmed death ligand 1 (PD-L1) expression, CD8+ T-cell infiltration in the tumor microenvironment, and clinical outcomes. II. To examine the association of specific genetic alterations (Braun et al., 2020) identified through whole-exome sequencing (WES) and transcriptional clusters (Motzer et al., 2020) identified via ribonucleic acid (RNA) sequencing, in relation to clinical outcomes. III. To characterize the phenotypes of circulating T cells, cytokines, chemokines, and angiokines at baseline and after neoadjuvant therapy to evaluate their association with therapeutic efficacy and clinical response. IV. To assess circulating tumor deoxyribonucleic acid (DNA) (ctDNA) to detect minimal residual disease (MRD) as a marker of therapeutic response and post-nephrectomy clinical outcomes. V. To investigate the correlation between circulating levels of soluble KIM-1 and clinical outcomes, including therapeutic response and post-nephrectomy clinical outcomes. OUTLINE: Patients receive botensilimab intravenously (IV) over 30 minutes on day 1 of weeks 1 and 7 and balstilimab IV over 30 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Patients undergo nephrectomy 12-16 weeks from the initiation of neoadjuvant therapy. Additionally, patients undergo blood sample collection and computed tomography (CT) throughout the study. After completion of study treatment, patients are followed every 3 months for up to 1 year post-nephrectomy.

Conditions

• Clear Cell Renal Cell Carcinoma
• Stage II Renal Cell Cancer AJCC v8
• Stage III Renal Cell Cancer AJCC v8
• Stage IV Renal Cell Cancer AJCC v8

Interventions

Type	Name	Description
BIOLOGICAL	Balstilimab	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
BIOLOGICAL	Botensilimab	Given IV
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Nephrectomy	Undergo nephrectomy
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2026-06-04
• Primary completion: 2027-08-30
• Completion: 2027-08-30
• First posted: 2026-04-08
• Last updated: 2026-04-13

Regulatory

• FDA-regulated drug study