Clinical Trials /

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

NCT04028245

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 downstaging

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Combination Spartalizumab and Canakinumab in Patients With Localized Clear Cell Renal Cell Carcinoma
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: AAAS2814
  • NCT ID: NCT04028245

Conditions

  • Carcinoma, Renal Cell

Interventions

DrugSynonymsArms
SpartalizumabPDR-001Spartalizumab and Canakinumab
CanakinumabACZ885Spartalizumab and Canakinumab

Purpose

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

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Spartalizumab and CanakinumabExperimentalSubjects with renal cell carcinoma will receive study treatment Q4 weeks x 2 doses prior to radical nephrectomy.
  • Spartalizumab
  • Canakinumab

Eligibility Criteria

        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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of subjects who proceed to radical nephrectomy
Time Frame:6 Weeks
Safety Issue:
Description:Feasibility of spartalizumab and canakinumab will be met if > 85% of patients proceed to radical nephrectomy (12 of 14).

Secondary Outcome Measures

Measure:Quantification of CD8 T cell infiltration into the tumor / peritumoral area infiltrates
Time Frame:6 Weeks
Safety Issue:
Description:To assess the immune response to combination canakinumab and spartalizumab. Tumor blocks and/or additional unstained slides will be collected for study-specific quantitative immunohistochemical evaluations. Cell infiltration into the kidney resection specimens will be quantified using immunohistochemical staining methods.
Measure:Quantification of immune cell populations (PMN-MDSC) in the tumor/ peritumoral area
Time Frame:6 Weeks
Safety Issue:
Description:To assess the immune response to combination canakinumab and spartalizumab. Tumor blocks and/or additional unstained slides will be collected for study-specific quantitative immunohistochemical evaluations. Cell infiltration into the kidney resection specimens will be quantified using immunohistochemical staining methods.
Measure:Objective tumor response rate
Time Frame:6 Weeks
Safety Issue:
Description:To assess the immune response to combination canakinumab and spartalizumab. By RECIST and by iRC, proportion of pathCR (pT0) and downstaging (decrease in size from baseline scans) will be calculated.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Charles G. Drake

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