Trial Title:
Advanced Renal Cell Cancer Combination ImmunoThErapy Clinical Trial
NCT ID:
NCT05928806
Condition:
Advanced Renal Cell Carcinoma
Conditions: Official terms:
Carcinoma, Renal Cell
Nivolumab
Ipilimumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Botensilimab
Description:
Botensilimab 75mg IV
Arm group label:
Arm A (botensilimab and balstilimab)
Other name:
AGEN1181
Intervention type:
Drug
Intervention name:
Balstilimab
Description:
Balstilimab 450mg IV
Arm group label:
Arm A (botensilimab and balstilimab)
Other name:
AGEN2034
Intervention type:
Drug
Intervention name:
Ipilimumab
Description:
Ipilimumab 1mg/kg IV
Arm group label:
Arm B (ipilimumab and nivolumab)
Other name:
Yervoy
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Nivolumab at induction: 3mg/kg IV Nivolumab at maintenance: 480mg IV
Arm group label:
Arm B (ipilimumab and nivolumab)
Other name:
Opdivo
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).
Criteria for eligibility:
Criteria:
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
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California San Diego
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Contact:
Last name:
Abbey Kenaston
Email:
akenaston@health.ucsd.edu
Investigator:
Last name:
Rana McKay, MD
Email:
Principal Investigator
Facility:
Name:
Yale University, Yale Cancer Center
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jialing Zhang
Email:
jialing.zhang@yale.edu
Investigator:
Last name:
David Braun, MD
Email:
Principal Investigator
Facility:
Name:
Georgetown University
Address:
City:
Washington
Zip:
20057
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gayle Cramer
Phone:
202-687-1116
Email:
gc604@georgetown.edu
Investigator:
Last name:
Michael Atkins, MD
Email:
Principal Investigator
Facility:
Name:
Winship Cancer Institute of Emory University
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Emily Setser
Email:
emily.jean.setser@emory.edu
Investigator:
Last name:
Mehmet Bilen, MD
Email:
Principal Investigator
Facility:
Name:
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Address:
City:
Indianapolis
Zip:
46202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sherry Beeler
Email:
srbeeler@iu.edu
Investigator:
Last name:
Jennifer King, MD
Email:
Principal Investigator
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kati Mack
Email:
kmack3@bidmc.harvard.edu
Investigator:
Last name:
David Einstein, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber - Partners Cancer Care, Inc
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Meredith Flynn
Email:
meredith_flynn@dfci.Harvard.edu
Investigator:
Last name:
Michael Serzan, MD
Email:
Principal Investigator
Facility:
Name:
John Theurer Cancer Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jane Hayes
Email:
Jane.Hayes@hmhn.org
Facility:
Name:
Columbia University Irving Medical Center
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jillian Gray
Email:
jg4400@cumc.columbia.edu
Investigator:
Last name:
Karie Runcie, MD
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rebecca Williams
Email:
Rebecca.Williams3@osumc.edu
Investigator:
Last name:
Yuanquan Aaron Yang, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Penn Medicine Abramson Cancer Center
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Charu Gandhi
Email:
charu.gandhi@pennmedicine.upenn.edu
Investigator:
Last name:
Naomi Balzar Haas, MD
Email:
Principal Investigator
Facility:
Name:
University of Texas Southwestern Medical Center
Address:
City:
Dallas
Zip:
75390
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amy Rowell
Email:
amy.rowell@utsouthwestern.edu
Investigator:
Last name:
Hans Hammers, MD, PhD
Email:
Principal Investigator
Start date:
September 25, 2023
Completion date:
October 12, 2026
Lead sponsor:
Agency:
Michael B. Atkins, MD
Agency class:
Other
Collaborator:
Agency:
Agenus Inc.
Agency class:
Industry
Collaborator:
Agency:
Georgetown University
Agency class:
Other
Source:
Hoosier Cancer Research Network
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05928806
