Nivolumab, Relatlimab and Ipilimumab versus Nivolumab and Ipilimumab for the Treatment of Untreated Stage IV Renal Cell Cancer
This phase II trial tests the safety and side effects of giving nivolumab, relatlimab and ipilimumab together and compares the effectiveness of the combination to nivolumab plus ipilimumab in treating patients with stage IV renal cell cancer (RCC) that have not yet received treatment (untreated). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving nivolumab, relatlimab and ipilimumab together may be safe, tolerable and may be more effective compared nivolumab plus ipilimumab in treating untreated stage IV RCC.
Inclusion Criteria
- Willing and able to provide a signed and dated written informed consent
- ≥ 18 years of age
- Confirmed diagnosis of RCC with a clear cell component
- Stage IV metastatic renal cell carcinoma per American Joint Committee on Cancer
- No prior systemic therapy for RCC. Prior neo/adjuvant systemic therapy is not allowed
- Karnofsky performance status ≥ 70%
- At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 • A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion
- White blood cell (WBC) ≥ 2,000 /uL (within 28 days prior to first dose of protocol-indicated treatment)
- Absolute neutrophil count (ANC) ≥ 1,500/uL (within 28 days prior to first dose of protocol-indicated treatment)
- Platelets ≥ 100,000/uL (within 28 days prior to first dose of protocol-indicated treatment)
- Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance > 30 mL/min (measured or calculated by Cockroft-Gault formula) (within 28 days prior to first dose of protocol-indicated treatment)
- Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who must have total bilirubin < 3.0 mg/dL) (within 28 days prior to first dose of protocol-indicated treatment)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (within 28 days prior to first dose of protocol-indicated treatment)
- Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment. An extension up to 72 hours prior to the start of study treatment is permissible in situations where results cannot be obtained within the standard 24-hour window * “Women of childbearing potential” (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal * Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes * If menopausal status is considered for the purpose of evaluating childbearing potential, women < 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential
- Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception from the time of signing consent, and for 23 weeks after their last dose of protocol-indicated treatment
Exclusion Criteria
- Prior systemic treatment for RCC of any type including neoadjuvant or adjuvant therapy is not allowed
- ≤ 28 days before first dose of protocol-indicated treatment: * Major surgery requiring general anesthesia
- ≤ 14 days before first dose of protocol-indicated treatment: * Radiosurgery or radiotherapy * Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery) * Active infection requiring infusion treatment
- Any history of or current central nervous system (CNS) metastases
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment * In the absence of active autoimmune disease, subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhalational) ≤ 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids ≤ 10 mg/day prednisone or equivalent daily (e.g. hormone replacement therapy needed in patients with hypophysitis)
- Active, known or suspected autoimmune disease * Subjects with type I diabetes mellitus; endocrine organ dysfunction (e.g., hypothyroidism) that are controlled and only requiring only hormone replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring systemic treatment; or conditions not expected by the investigator to recur in the absence of an external trigger are permitted to enroll
- Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements
- History of myocarditis, regardless of etiology
- Troponin T (TnT) or I (TnI) > 2 x institutional upper limit of normal (ULN) * Participants with TnT or TnI levels between > 1 x to 2 x ULN will be permitted if repeat levels within 24 hours are ≤ 1 x ULN. If TnT or TnI levels are between > 1 x to 2 x ULN within 24 hours, the participant may undergo a cardiac evaluation and be considered for treatment, based on a favorable benefit/risk assessment by the Investigator. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2 x ULN, the participant may undergo a cardiac evaluation and be considered for treatment, based on a favorable benefit/risk assessment by the investigator
- Treatment with any live/attenuated vaccine within 30 days of first study treatment
Additional locations may be listed on ClinicalTrials.gov for NCT06708949.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of nivolumab, relatlimab and ipilimumab in patients with untreated advanced RCC.
II. To assess the objective response rate (ORR) of nivolumab, relatlimab and ipilimumab in patients with untreated advanced RCC.
SECONDARY OBJECTIVE:
I. To estimate progression free survival (PFS), duration of response (DOR), primary progressive disease (PD) rate, treatment-free survival, overall survival (OS) and immune related adverse event (irAE) rate of nivolumab, relatlimab and ipilimumab combination in untreated advanced RCC.
EXPLORATORY OBJECTIVE:
I. To investigate the association of baseline and on-treatment tumor/microenvironment characteristics (e.g. deoxyribonucleic acid [DNA], ribonucleic acid [RNA] and protein expression) with clinical outcomes.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (TRIPLET ARM): Patients receive nivolumab intravenously (IV) over 60 minutes on day 1 of each cycle, relatlimab IV over 60 minutes on day 1 of each cycle and ipilimumab IV over 30 minutes of every odd-numbered cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Patients also undergo a brain scan at screening and bone scan at screening and with signs or symptoms of bone metastases. Additionally, patients may undergo tissue biopsy of metastatic site at screening and at cycle 4.
ARM II (DOUBLET ARM): Patients receive nivolumab IV over 60 minutes on day 1 of each cycle and ipilimumab IV over 30 minutes of cycles 1-4. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, and CT or MRI throughout the study. Patients also undergo a brain scan at screening and bone scan at screening and with signs or symptoms of bone metastases. Additionally, patients may undergo tissue biopsy of metastatic site at screening and at cycle 5.
After completion of study treatment, patients are followed up at 28 days and at 100 days for control arm and 135 days for investigational arm, then every 12 weeks for up to 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorEric Jonasch
- Primary ID2024-1337
- Secondary IDsNCI-2025-01553
- ClinicalTrials.gov IDNCT06708949