Neoadjuvant Spartalizumab and Canakinumab for the Treatment of Patients with Localized Kidney Cancer, SPARC-1 Trial
This pilot phase Ib trial studies the side effects and how well spartalizumab and canakinumab work in treating patients with kidney cancer that that has not spread to other parts of the body (localized). Immunotherapy with monoclonal antibodies, such as spartalizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with canakinumab may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. Giving spartalizumab and canakinumab before surgery may work better than giving no treatment before surgery in treating kidney cancer.
Inclusion Criteria
- Radiographically consistent with OR histologically confirmed clear cell RCC or predominantly clear cell RCC
- Localized non-metastatic RCC T1b-T4N, any M0 or T any N1M0
- Schedule to undergo either partial or radical nephrectomy as part of the treatment plan
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Age ≥ 18 years old at time of consent
- If a patient is infected with human immunodeficiency virus (HIV), the patient must be healthy and have a low risk of autoimmune deficiency syndrome (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
- White blood cell count (WBC) >= 3.0 K/mm^3
- Absolute neutrophil count (ANC) >= 1.5 K/mm^3
- Platelets >= 100 K/mm^3
- Hemoglobin (Hgb) >= 9 g/dL
- Serum total bilirubin: =< 1.5 x upper limit of normal (ULN)
- Alanine transferase (ALT) and aspartate transaminase (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 Health Insurance Portability and Accountability Act (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
- All races and ethnic groups are eligible for this trial
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 of 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
- 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 nonmelanoma 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
Additional locations may be listed on ClinicalTrials.gov for NCT04028245.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. 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:
I. To assess the immune response to combination canakinumab and spartalizumab:
Ia. Quantification of CD8 T cell infiltration into the tumor/peritumoral area.
Ib. Quantification of immune cell populations including polymorphonuclear myeloid derived suppressor cells (PMN-MDSC) in the tumor/peritumoral area.
II. To assess anti-tumor activity as measured by pathologic downstaging.
IIa. Objective tumor response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] and by immune-modified Response Evaluation Criteria in Solid Tumors [iRECIST]), proportion of pathologic complete response (pathCR) (pT0) and downstaging (decrease in size from baseline scans).
EXPLORATORY OBJECTIVES:
I. To assess anti-tumor efficacy as measured by pathologic response:
Ia. Pathological response graded according to standard criteria including pathologic complete response and positive surgical margins.
Ib. Metastases free survival up to 12 months post-operatively using Kaplan Meier, logrank test, or Cox Proportional Hazards where appropriate.
II. To evaluate potential predictive biomarkers for treatment response.
IIa. Pre-treatment (where available) and post-treatment tumor PD-L1 expression measured using immunohistochemistry (IHC).
IIb. Potential association between PD-L1 expression and pathologic response assessed using Fisher’s exact test or other methodology such as logistical regression based multivariable analysis for binary response data as appropriate.
IIc. Quantification of immune cell infiltrates by IHC.
III. To quantify peripheral blood inflammatory markers and perform cytokine analysis on peripheral blood:
IIIa. Sera collection for circulating cytokine analysis and serum hsCRP at 0, 2, 4, and 6 weeks on treatment (IL-1 and IFN-gamma will be included in the panel, exact cytokine list will be selected based on methodology optimization).
IIIb. Peripheral blood mononuclear cell (PBMC) T cell subset analysis and 0 and 6 weeks (day of surgery) on therapy.
IV. Renal cell carcinoma (RCC) tumor gene expression profiling.
IVa. Gene expression profiling (including PD-1, PD-L1, and IL-1beta expression) performed at Columbia.
OUTLINE:
Patients receive canakinumab intravenously (IV) over 120 minutes, and within 30 minutes of completion of canakinumab, receive spartalizumab IV over 30 minutes. Treatment continues every 4 weeks for 2 doses in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care radical nephrectomy on day 43. Additionally, patients undergo optional biopsy at screening and blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
After the completion of study treatment, patients are followed up at 30 and 90 days, and every 3 months up to 1 year afterwards.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationNYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Principal InvestigatorKarie Runcie
- Primary IDAAAS2814
- Secondary IDsNCI-2020-01069
- ClinicalTrials.gov IDNCT04028245