A Pilot Study of Neoadjuvant Combination Spartalizumab and Canakinumab Prior to Radical Nephrectomy in Patients With Localized Clear Cell Renal Cell Carcinoma (SPARC-1 Trial)

Description

Primary Objective: * To confirm the safety and feasibility of canakinumab and spartalizumab (PDR-001) administered using a standard dose / schedule in the neo-adjuvant setting in renal cell carcinoma Secondary Objectives: * To assess the immune response to combination canakinumab and spartalizumab * To assess anti-tumor activity as measured by pathologic downstagingPatients with localized and non-metastatic Renal Cell Carcinoma (RCC) represent an "at-need" population who would benefit from immunotherapy earlier in their disease course with a programmed cell death protein 1(PD-1) therapy combined with a second immunotherapy agent. A logical next step is to pursue the combination of an anti- programmed cell death protein 1(PD1) therapy with cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockade extrapolating from recent successes in the metastatic setting. The primary concern with previous approaches and studies is that CTLA-4 based therapy is associated with increased risk of

Trial Eligibility

Inclusion Criteria: * Radiographically consistent with or histologically confirmed clear cell RCC or predominantly clear cell RCC * Localized non-metastatic RCC T1b-T4NanyM0 or TanyN1M0) * Schedule to undergo either partial or radical nephrectomy as part of the treatment plan * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 * Age ≥ 18 years old at time of consent * HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes as defined by the following * Cluster of differentiation 4 (CD4+) T cell counts ≥ 350 cells/microliter OR undetectable HIV viral load * no history of AIDS-defining opportunistic infection in the last year * Normal organ and marrow function as defined below: * White blood cell count (WBC) \> 3.0 K/mm3 * Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 * Platelets ≥ 100 K/mm3 * Hemoglobin (Hgb) ≥ 9 g/dL * Serum total bilirubin: ≤ 1.5 x upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN * Serum creatinine ≤ 1.5 x ULN or serum creatinine \> 1.5 - 3 x ULN if calculated * creatinine clearance (CrCl) is ≥ 30 mL/min * For patients with known chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * For patients with a history of hepatitis C virus (HCV) infection, the infection must be treated and cured * Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent) * Willingness to use barrier contraception from the time of first dose of canakinumab and spartalizumab until 120 days after surgical intervention Exclusion Criteria: * Presence of distant metastases * Presence of active, known or suspected autoimmune disease. * No patients with documented, active infections, treated or untreated, may be included in this study * Use of any live vaccines against infectious disease within 4 weeks of initiation ot study treatment. * Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways * Prior treatment for RCC including surgery, radiation, thermoablation, or systemic therapy * Surgery within 28 days of starting study treatment * Prior treatment with any antibody or drug targeting T cell costimulation or immune checkpoint pathways (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, etc) * Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. Note: Topical, inhaled, nasal and ophthalmic steroids are allowed * Allogenic bone marrow or solid organ transplant * History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction * History or current interstitial lung disease or non-infectious pneumonitis requiring the use of home oxygen * History of severe hypersensitivity reaction to other monoclonal antibodies * Current signs or symptoms of severe progressive or uncontrolled, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or cardiac disease other than directly related to RCC * Positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA) * History of known or suspected autoimmune disease with the following exceptions: * Vitiligo * Resolved childhood atopic dermatitis * Psoriasis (with exception of psoriatic arthritis) not requiring systemic treatment (within the past 2 years). * Patients with Grave's disease or Hashimoto's thyroiditis that are now euthyroid clinically and by laboratory testing. * History of malignancy within the last 2 years, with the exception of non-melanoma skin cancers and superficial bladder cancer * Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate

Study Info

Interventions

Locations Recruiting

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