A Study of Combination Spartalizumab and Canakinumab in Patients With Localized Clear Cell Renal Cell Carcinoma

Introduction

• Org Study ID: AAAS2814
• NTC ID: NCT04028245
• Lead Sponsor Name: Columbia University
• Status: RECRUITING

Conditions

• Clear Cell Renal Cell Carcinoma

Brief Summary

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 downstaging

Eligibility Criteria

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