Advanced Renal Cell Cancer Combination ImmunoThErapy Clinical Trial

NCT05928806 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU22-587
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 13

Brief Summary

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).

Conditions

Advanced Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Determine the objective response rate (ORR) of botensilimab + balstilimab in patients with treatment naïve metastatic ccRCC relative to the ORR of patients treated with ipilimumab + nivolumab.

  ORR is defined as the proportion of the subjects in the analysis population who have a CR or PR per RECIST 1.1.

  5 years

Secondary Outcomes (4)

• Determine Duration of response (DOR) for patients who have a CR or PR

  5 years

• Determine the 12- & 24-month landmark progression free survival (PFS)

  5 years

• Determine treatment free survival (TFS)

  5 years

• Determine the safety of botensilimab + balstilimab relative to ipilimumab + nivolumab

  5 years

Study Arms (2)

Arm A (botensilimab and balstilimab)

EXPERIMENTAL

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.

Drug: Botensilimab; Drug: Balstilimab

Arm B (ipilimumab and nivolumab)

ACTIVE COMPARATOR

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).

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

Ipilimumab 1mg/kg IV

Also known as: Yervoy

Arm B (ipilimumab and nivolumab)

Nivolumab DRUG

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

Also known as: Opdivo

Arm B (ipilimumab and nivolumab)

Botensilimab DRUG

Botensilimab 75mg IV

Also known as: AGEN1181

Arm A (botensilimab and balstilimab)

Balstilimab DRUG

Balstilimab 450mg IV

Also known as: AGEN2034

Arm A (botensilimab and balstilimab)

Eligibility Criteria

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

You may qualify if:

• Patient must have ECOG PS of ≤ 2 within 28 days of C1D1.
• Age ≥ 18 years old at the time of informed consent.
• 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.
• 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.
• 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
• 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

You may not qualify if:

• Prior adjuvant or systemic therapy for RCC.
• 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.
• Radiotherapy within 2 weeks prior to Cycle 1 Day 1.
• 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).
• 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.
• 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.
• 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.
• 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.
• 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.
• Uncontrolled adrenal insufficiency based on investigator discretion.
• Active infection requiring systemic therapy within 14 days of Cycle 1 Day 1.
• 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.
• Legally incapacitated or has limited legal capacity.
• Pregnant or breastfeeding.
• Prior allogeneic tissue/solid organ transplant, except for corneal transplants.

Sponsors & Collaborators

• Michael B. Atkins, MD: lead
• Agenus Inc.: collaborator
• Georgetown University: collaborator

Study Sites (13)

University of California San Diego

La Jolla, California, 92093, United States

Location

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber - Partners Cancer Care, Inc

Boston, Massachusetts, 02215, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Cornell University

Ithaca, New York, 14850, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Interventions

balstilimab; Ipilimumab; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michael B Atkins, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: June 23, 2023
• First Posted: July 3, 2023
• Study Start: September 25, 2023
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): November 10, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

US (13)