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
Patients 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 PD-1
therapy combined with a second immunotherapy agent. A logical next step is to pursue the
combination of an anti-PD1 therapy with 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 autoimmune side effects which
potentially could delay a curative surgery. Clearly, the neoadjuvant setting in RCC
represents an ideal space to evaluate novel I/O combination strategies aside from CTLA-4
blockade.
This study intends 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. This is a single-center, single arm, open-label pilot study evaluating the
feasibility, safety, anti-tumor effect, and immunogenicity of neoadjuvant canakinumab and
spartalizumab given prior to radical nephrectomy in patients with localized renal cell
carcinoma. Patients will be recruited from the outpatient Urology clinic.
Eligible patients will receive canakinumab at a dose of 300 mg Q4weeks and spartalizumab at
400 mg Q4weeks IV. Approximately 14 days after the last dose of canakinumab and
spartalizumab, patients with proceed to radical nephrectomy, and nephrectomy tissue will be
examined for the secondary endpoints. Follow-up evaluation for adverse events will occur 30
days and 90 days after surgery. Patients will then be followed by their urologists and
oncologist according to standard institutional practices, but will require repeat labs every
3 months along with standard of care surveillance imaging.
Inclusion Criteria:
- Histologically confirmed clear cell or predominantly clear cell RCC
- Non-metastatic (localized) RCC that is clinical stage T2 and above, or clinical N1
disease with any T stage
- Schedule to undergo either partial or radical nephrectomy as part of the treatment
plan
- ECOG 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
- 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 ULN
- ALT and 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
- 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 3 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
- Known prior or current history of HIV and/or hepatitis B/C
