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

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Charles G. Drake; Matthew Dallos
• Collaborator: Novartis
• Treatments: Antibodies, Monoclonal; Spartalizumab

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