Clear Cell Renal Cell CarcinomaPhase 2NCT07516366
Testing the Safety and Feasibility of Immunotherapy Drugs, Botensilimab and Balstilimab, Before Surgery for Clear Cell Renal Cell Carcinoma, NEO RoBOT Trial
A Phase 2 study testing Balstilimab, Biospecimen Collection and Botensilimab in people with Clear Cell Renal Cell Carcinoma and Stage II Renal Cell Cancer AJCC v8, run by National Cancer Institute (NCI) at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear Cell Renal Cell Carcinoma, Stage II Renal Cell Cancer AJCC v8, Stage III Renal Cell Cancer AJCC v8
- What is being tested?
- Balstilimab, Biospecimen Collection and Botensilimab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 5 sitesUnited States
- Study dates
- 17 May 2027to 31 Dec 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have biopsy-confirmed, non-metastatic, high-risk renal cell carcinoma (RCC) with a clear cell component, defined as clinical stage T2N0, T3N0, T4N0, or any T stage with N1 disease (i.e., T2a-T4NanyM0 or TanyN1M0), and no evidence of metastatic disease
- Participants with resectable RCC are eligible, including those who have previously undergone surgical resection for RCC and subsequently developed resectable recurrent disease. Patients must be candidates for further curative-intent surgical resection. Prior systemic therapy for RCC (including VEGF-targeted therapy, immune checkpoint inhibitors, HIF-2α inhibitors, or other systemic anticancer therapies) is not allowed
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab in combination with balstilimab in patients < 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
- Patients must be considered suitable for curative-intent surgical resection of RCC, including radical or partial nephrectomy, as determined by the urology team and the treating physician according to standard clinical guidelines
- Absolute neutrophil count ≥ 1,000/mcL
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- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN
- Glomerular filtration rate (GFR) 50 mL/min (calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- 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. Also including a prior history of renal cell carcinoma
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
- Patients must be scheduled to undergo either partial or radical nephrectomy as part of treatment plan
- The effects of botensilimab and balstilimab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of botensilimab and balstilimab administration. All patients of childbearing potential must undergo a blood or urine pregnancy test within 14 days prior to receiving the first dose of botensilimab and balstilimab to confirm they are not pregnant. If dosing is delayed beyond this window, the pregnancy test must be repeated to ensure results remain current
- Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
- Availability of pre-treatment archival slides or tissue blocks is required for inclusion in the study
Who cannot join
- Patients who have suspected or proven metastatic renal cell carcinoma
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to botensilimab or balstilimab
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because botensilimab and balstilimab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with botensilimab or balstilimab, breastfeeding should be discontinued if the mother is treated with botensilimab or balstilimab
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- Patients without a clear cell component in their baseline kidney biopsy or non-clear cell renal cell carcinoma (RCC) are excluded from this study
- Patients who have received prior treatment with an anti-PD-1, anti-programmed cell death protein ligand 1 (PD-L1), anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Patients who have undergone major surgery within 28 days prior to the start of the study
- Patients with any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications within 14 days prior to first dose of study drug; the exception would be for syndromes which would not be expected to recur in the absence of an external trigger. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- Patients with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
- Patients with a baseline corrected QT interval (Fridericia's corrected QT interval [QTcF]) > 480 ms on screening electrocardiogram (ECG), a history of congenital long QT syndrome, or clinically significant cardiac arrhythmias will be excluded
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu
Jack Masur
- Recruiting
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Site Public Contact, 352-273-8010
Daniel V. Araujo
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Michael Daneshvar
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Adanma Anji Ayanambakkam Attanathi
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Michael Daneshvar
About this study
Official title: Pilot Phase II Trial Evaluating Safety and Feasibility of Neoadjuvant Botensilimab and Balstilimab in Clear Cell Renal Cell Carcinoma (NEO RoBOT)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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.
- 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
- Being tested
- Balstilimab, Biospecimen Collection, Botensilimab, Computed Tomography, Nephrectomy
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BalstilimabBiological
Also called AGEN 2034, AGEN-2034, AGEN2034
Given IV
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
BotensilimabBiological
Also called AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
NephrectomyProcedure or surgery
Undergo nephrectomy
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (botensilimab, balstilimab) | Experimental | Patients receive botensilimab 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 CT throughout the study. Receives: Biological: Balstilimab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Procedure: Nephrectomy; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients successfully completing neoadjuvant treatment and undergoing planned definitive surgical resection of primary tumor (radical or partial nephrectomy) without significant treatment related delays
The intervention will be considered feasible if at least 80% of enrolled patients (13 out of 16) successfully undergo planned radical or partial nephrectomy following treatment.
Measured: Up to 1 year post-surgery
Incidence and severity of treatment-related adverse events
Will be analyzed descriptively using frequencies and proportions, stratified by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Measured: Up to 30 days after last dose of study treatment
Incidence and severity of surgical complications
Will be summarized using the Clavien-Dindo Classification.
Measured: Up to 30 days after surgery
Secondary outcomes (6)
Objective response rate (ORR)
Will be defined as the proportion of patients achieving a complete response or partial response of the primary tumor as defined by Response Evaluation Criteria for Solid Tumors 1.1 criteria. ORR will be summarized as a proportion with a 95% confidence interval (CI) using the Clopper-Pearson method (exact binomial CIs), and analyses conducted on both the intention-to-treat and per-protocol populations.
Measured: After neoadjuvant treatment, assessed up to 1 year post-nephrectomy
Major pathologic response (MPR) rate
Will be defined as the proportion of patients with < 10% viable tumor cells. MPR rate will be determined through centralized pathology review of the surgical specimen, summarized as proportions with 95% CIs using Clopper-Pearson method, and a descriptive comparison between response categories will be presented.
Measured: Up to 1 year post-surgery
Partial pathologic rate (PPR) rate
Will be defined as the proportion of patients with < 50% viable tumor cells in the tumor bed of the resected specimen, will be assessed. PPR rate will be determined through centralized pathology review of the surgical specimen, summarized as proportions with 95% CIs using Clopper-Pearson method, and a descriptive comparison between response categories will be presented.
Measured: Up to 1 year post-surgery
Rates of distant metastasis
Will be defined as proportion of patients experiencing distant metastatic disease. Will be summarized as proportions with 95% CIs.
Measured: Up to 1 year post-surgery
Rates of local recurrence
Will be defined as proportion of patients experiencing local recurrence after treatment. Will be summarized as proportions with 95% CIs.
Measured: Up to 1 year post-surgery
Disease-free survival (DFS)
DFS will be analyzed using the Kaplan-Meier method for medians and survival curves, with subgroup comparisons by log-rank tests and hazard ratios estimated using Cox proportional hazards models.
Measured: From surgery to the first documented evidence of disease recurrence (local, regional, or distant metastasis) or death from any cause, assessed up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2026
- Study start17 May 2027 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Adanma Anji Ayanambakkam Attanathi, Principal investigator, Yale University Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07516366
- Sponsor's protocol ID
- NCI-2026-02194
- Other IDs
- NCI-2026-02194, 10743, 10743, UM1CA186689
- Status last verified
- Oct 2026
- First submitted
- 7 Apr 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.