RECRUITING

Advanced Renal Cell Cancer Combination ImmunoThErapy Clinical Trial

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

Phase 2 Advanced Renal Cell Cancer Combination ImmunoThErapy Clinical Trial

Quick Facts

Study Start:2023-09-25

Study Completion:2026-10-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05928806

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 * 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 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.	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.

Inclusion Criteria

Exclusion 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
* 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 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.

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.

Contacts and Locations

Study Contact

Michael B Atkins, MD

CONTACT

202-687-2795

mba41@georgetown.edu

Rebecca Mottier

CONTACT

317-634-5842

rmottier@hoosiercancer.org

Principal Investigator

Michael B Atkins, MD

PRINCIPAL_INVESTIGATOR

Georgetown University

Study Locations (Sites)

University of California San Diego

La Jolla, California, 92093

United States

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520

United States

Georgetown University

Washington, District of Columbia, 20057

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322

United States

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

United States

Dana-Farber - Partners Cancer Care, Inc

Boston, Massachusetts, 02215

United States

John Theurer Cancer Center

Hackensack, New Jersey, 07601

United States

Columbia University Irving Medical Center

New York, New York, 10032

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: Michael B. Atkins, MD

Michael B Atkins, MD, PRINCIPAL_INVESTIGATOR, Georgetown University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-25

Study Completion Date2026-10-12

Study Record Updates

Study Start Date2023-09-25

Study Completion Date2026-10-12

Terms related to this study

Additional Relevant MeSH Terms

Advanced Renal Cell Carcinoma