Advanced Renal Cell Cancer Combination ImmunoThErapy Clinical Trial

NCT ID: NCT05928806

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-25

Study Completion Date

2026-10-12

Brief Summary

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This study is a randomized, open label, multicenter Phase II trial to evaluate the efficacy and safety of botensilimab (a novel Fc enhanced Tree depleting anti-CTLA4) and balstilimab (a novel anti-PD1) relative to ipilimumab and nivolumab in treatment naïve patients with metastatic ccRCC. The study will plan to enroll 120 eligible patients randomized in a 2:1 fashion to Arm A and Arm B. Patients in all IMDC Risk Groups are included. This study utilizes a Simon's two stage design which is described in the protocol. Patients randomized to Arm A will receive botensilimab in combination with balstilimab. Patients randomized to Arm B will receive ipilimumab in combination with nivolumab. Study treatment on both arms will continue until toxicity, disease progression or a maximum of 96 total weeks (12 weeks induction, 84 weeks maintenance).

Detailed Description

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Conditions

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Advanced Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (botensilimab and balstilimab)

Arm A subjects will receive 2 cycles of induction treatment with each cycle lasting 6 weeks. Cycle 1 will consist of botensilimab 75mg IV in combination with balstilimab 450mg IV on Day 1 and Day 22. Cycle 2 will consist of balstilimab 450mg IV ONLY on Day 1 and Day 22. Botensilimab will NOT be given in Cycle 2. Subjects will receive 7 cycles of maintenance treatment with each cycle lasting 12 weeks. Cycles 3 and 4 will consist of botensilimab 75mg IV on Day 1 in combination with balstilimab 450mg IV on Day 1, 22, 43 and 64. Cycles 5-9 will consist of balstilimab alone 450 mg IV on Day 1, 22, 43 and 64.

Group Type EXPERIMENTAL

Botensilimab

Intervention Type DRUG

Botensilimab 75mg IV

Balstilimab

Intervention Type DRUG

Balstilimab 450mg IV

Arm B (ipilimumab and nivolumab)

Arm B subjects will receive 2 cycles of induction treatment with each cycle lasting 6 weeks. Cycle 1 and 2 will consist of ipilimumab 1 mg/kg IV and nivolumab 3 mg/kg on Day 1 and 22. Subjects will receive 7 cycles of maintenance treatment with each cycle lasting 12 weeks. Nivolumab 480mg IV will be given on Day 1, 29 and 57 of each cycle (every 4 weeks).

Group Type ACTIVE_COMPARATOR

Ipilimumab

Intervention Type DRUG

Ipilimumab 1mg/kg IV

Nivolumab

Intervention Type DRUG

Nivolumab at induction: 3mg/kg IV Nivolumab at maintenance: 480mg IV

Interventions

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Botensilimab

Botensilimab 75mg IV

Intervention Type DRUG

Balstilimab

Balstilimab 450mg IV

Intervention Type DRUG

Ipilimumab

Ipilimumab 1mg/kg IV

Intervention Type DRUG

Nivolumab

Nivolumab at induction: 3mg/kg IV Nivolumab at maintenance: 480mg IV

Intervention Type DRUG

Other Intervention Names

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AGEN1181 AGEN2034 Yervoy Opdivo

Eligibility Criteria

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Inclusion Criteria

1. Patient must have ECOG PS of ≤ 2 within 28 days of C1D1.
2. Age ≥ 18 years old at the time of informed consent.
3. Patient must have histological confirmation of renal carcinoma with clear cell component including advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC.
4. Patient must have measurable disease by CT or MRI per RECIST 1.1 criteria. Radiated lesions cannot be used as measurable lesions unless there is clear evidence of progression.
5. Patient must have defined IMDC risk categorization of either favorable, intermediate or poor based on clinical variables of increased risk (below).

* No risk factors (0) = favorable risk
* 1-2 risk factors = intermediate risk
* ≥ 3 risk factors = poor risk

NOTE: Patients with all IMDC risk factors are eligible, but will be stratified according to IMDC risk, and initial analysis will be based on the IMDC intermediate and poor risk patients. IMDC Risks:
* KPS less than 80%
* Less than 1 year from diagnosis including original localized disease to randomization(if applicable)
* Hemoglobin less than the lower limit of normal
* Corrected calcium concentration greater than 10 mg/dL
* ANC greater than the ULN
* Platelet count greater than the ULN
6. Patient must have either a formalin-fixed, paraffin-embedded (FFPE) tissue block or at least 10 (preferably 20) unstained tumor tissue sections, obtained from a metastatic lesion, preferably within 3 months or no more than 12 months with an associated pathology report. This tissue must be identified prior to registration. Confirmation of sufficient archival tissue must be obtained after informed consent and the tissue must be shipped to the appropriate lab by end of Cycle 2. Biopsies should be excisional, incisional, or core needle. Fine needle aspiration is unacceptable for submission. Biopsies of bone lesions that do not have a soft tissue component are also unacceptable for submission. This sample is required to be eligible for the trial. If a patient is having a standard of care biopsy, part of that sample may be utilized for eligibility.
7. Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.

* Hematological
* White blood cell (WBC) ≥ 2,000/uL
* Absolute Neutrophil Count (ANC) ≥ 1,000/uL; without growth factor support
* Hemoglobin (Hgb) ≥ 8.0 g/dL; ≥ 7 days without PRBC transfusion.
* Platelets ≥ 75,000/uL; without platelet transfusion
* Renal
* Calculated creatinine clearance (CrCl)1 ≥ 40 mL/min
* Hepatic
* Total Bilirubin ≤ 1.5 × upper limit of normal (ULN) \*EXCEPT participants with Gilbert Syndrome who must have a Total Bilirubin level of \< 3.0 x ULN
* Aspartate aminotransferase (AST) ≤ 3.0 × ULN
* Alanine aminotransferase (ALT) ≤ 3.0 × ULN
8. HIV positive patients may be eligible if either:

* Patients with CD4 \> 200 cells/mm3 OR
* Patients with HIV viral load undetectable.
9. Active HBV or active HCV patients may be eligible if:

* Patients with HBV infection are eligible if hepatitis B surface antigen and HBV DNA are negative.
* Patients with HCV infection are eligible if HCV RNA is negative.
10. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 1 week prior to Cycle 1 Day 1.
11. WOCBP must agree to follow instructions for method(s) of contraception.
12. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception.

Exclusion Criteria

1. Prior adjuvant or systemic therapy for RCC.
2. Prior treatment with an anti-PD1 or anti-PDL1 agent, anti-CTLA4 antibody or a VEGFR TKI or anti-VEGF antibody including in the adjuvant setting.
3. Radiotherapy within 2 weeks prior to Cycle 1 Day 1.
4. Expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
5. Currently known active and definitive CNS metastases. Patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery (SRS)) may be eligible. Patients must not have taken any steroids ≤ 2 weeks prior to randomization for the purpose of managing their brain metastases. Repeat imaging after SRS or surgical resection is not required so long as baseline MRI is within 4 weeks of registration. Patients with multiple brain metastases treated with SRS (with or without WBRT), are not excluded. Patients with definitive CNS metastases treated with only WBRT are ineligible. Patients with potential CNS metastases that are too small for treatment with either SRS or surgery (e.g. 1-2 mm) and/or are of uncertain etiology are potentially eligible, but need to be discussed with and approved by the sponsor-investigator.
6. Persistent toxicity of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade \> 1 severity that is related to prior therapy. NOTE: Sensory neuropathy or alopecia of Grade ≤ 2 are acceptable.
7. Known severe (Grade ≥ 3) hypersensitivity reactions to fully human monoclonal antibodies, antibody, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with steroids; or has a history of interstitial lung disease, any history of anaphylaxis, or uncontrolled asthma.
8. Known condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \<10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. NOTE: Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed.
9. Active known or suspected autoimmune disease that required systemic treatment within 2 years of the start of study drug (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (e.g., celiac disease) are permitted to enroll.
10. Uncontrolled adrenal insufficiency based on investigator discretion.
11. Active infection requiring systemic therapy within 14 days of Cycle 1 Day 1.
12. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
13. Legally incapacitated or has limited legal capacity.
14. Pregnant or breastfeeding.
15. Prior allogeneic tissue/solid organ transplant, except for corneal transplants.
16. Major surgery (e.g., nephrectomy) less than 28 days prior to Cycle 1 Day 1.
17. Prior malignancy active within the previous 2 years from screening except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
18. Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator, would preclude the participant from adhering to the protocol or would increase the risk associated with study participation or study treatment administration or interfere with the interpretation of safety results.
19. Receipt of a live/attenuated vaccine within 30 days of first study treatment. The use of inactivated seasonal influenza vaccines (eg, Fluzone®) will be permitted on study without restriction.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Agenus Inc.

INDUSTRY

Sponsor Role collaborator

Georgetown University

OTHER

Sponsor Role collaborator

Michael B. Atkins, MD

OTHER

Sponsor Role lead

Responsible Party

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Michael B. Atkins, MD

Sponsor-Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Michael B Atkins, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University

Locations

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University of California San Diego

La Jolla, California, United States

Site Status RECRUITING

Yale University, Yale Cancer Center

New Haven, Connecticut, United States

Site Status RECRUITING

Georgetown University

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber - Partners Cancer Care, Inc

Boston, Massachusetts, United States

Site Status RECRUITING

John Theurer Cancer Center

Hackensack, New Jersey, United States

Site Status RECRUITING

Cornell University

Ithaca, New York, United States

Site Status RECRUITING

Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michael B Atkins, MD

Role: CONTACT

Phone: 202-687-2795

Email: [email protected]

Rebecca Mottier

Role: CONTACT

Phone: 317-634-5842

Email: [email protected]

Facility Contacts

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Abbey Kenaston

Role: primary

Jialing Zhang

Role: primary

Gayle Cramer

Role: primary

Emily Setser

Role: primary

Sherry Beeler

Role: primary

Kati Mack

Role: primary

Meredith Flynn

Role: primary

Oncology Clinical Research Referral Office Research Referral Office

Role: primary

Escarleth Fernandez

Role: primary

Jillian Gray

Role: primary

Rebecca Williams

Role: primary

Charu Gandhi

Role: primary

Amy Rowell

Role: primary

Other Identifiers

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HCRN GU22-587

Identifier Type: -

Identifier Source: org_study_id