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

Plain English Summary

Testing the Safety and Feasibility of Immunotherapy Drugs, Botensilimab and Balstilimab, Before Surgery for Clear Cell Renal Cell Carcinoma, NEO RoBOT Trial is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying 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. This trial tests if two immunotherapy drugs, botensilimab and balstilimab, can be safely given before surgery for a specific type of kidney cancer. It is for patients with high-risk, non-spreading clear cell renal cell carcinoma who are scheduled for surgery. Participation involves receiving the study drugs intravenously before surgery, with regular check-ups and tests. Standard treatment typically involves surgery alone; this trial explores adding immunotherapy beforehand. The trial aims to enroll 16 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients must have a confirmed diagnosis of clear cell renal cell carcinoma that has not spread. Must be 18 years or older and in good general health, able to undergo surgery. Certain pre-existing conditions or recent cancer treatments may exclude you. Requires availability of tumor tissue for study. This trial is studying 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, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measure how many patients can safely receive the study drugs before surgery and how many experience significant side effects or surgical complications, indicating the feasibility The specific primary outcome measures are: 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 (Up to 1 year post-surgery); Incidence and severity of treatment-related adverse events (Up to 30 days after last dose of study treatment); Incidence and severity of surgical complications (Up to 30 days after surgery). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for more effective treatments for high-risk kidney cancer before surgery, potentially improving outcomes by using the body's immune system to fight the cancer. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets 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, where improved treatment options are needed.

Investor Insight

This trial explores novel immunotherapy combinations in a significant cancer indication, representing a potential advancement in neoadjuvant cancer therapy and a competitive area for pharmaceutical in Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you, considering your specific cancer stage and overall health. Understand that you will receive study drugs before your planned surgery, and will have regular monitoring. Be prepared for potential side effects of immunotherapy and surgery. The trial is being conducted at multiple sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 16 participants

Interventions

• BIOLOGICAL: Balstilimab — Given IV
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• BIOLOGICAL: Botensilimab — Given IV
• PROCEDURE: Computed Tomography — Undergo CT
• PROCEDURE: Nephrectomy — Undergo nephrectomy

Primary Outcomes

• 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 (Up to 1 year post-surgery)
• Incidence and severity of treatment-related adverse events (Up to 30 days after last dose of study treatment)
• Incidence and severity of surgical complications (Up to 30 days after surgery)

Secondary Outcomes

• Objective response rate (ORR) (After neoadjuvant treatment, assessed up to 1 year post-nephrectomy)
• Major pathologic response (MPR) rate (Up to 1 year post-surgery)
• Partial pathologic rate (PPR) rate (Up to 1 year post-surgery)
• Rates of distant metastasis (Up to 1 year post-surgery)
• Rates of local recurrence (Up to 1 year post-surgery)

Full Eligibility Criteria

Inclusion Criteria:

* 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
* 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
* 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/1.73 m\^2
* 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

Exclusion Criteria:

* 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
* 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 for RCC, inc

Frequently Asked Questions

Related Conditions

• Kidney Cancer
• Renal Cell Carcinoma
• Clear Cell Renal Cell Carcinoma
• Urothelial Carcinoma
• Bladder Cancer
• Prostate Cancer
• Oncology
• Immunotherapy
• Neoadjuvant Therapy
• Targeted Therapy

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