Critères d’exclusion :
E1. Concurrent use of any other approved or investigational antineoplastic agent;
E2. Prior or concurrent treatment with any antibody targeting PD1, PDL1, PDL2 or CTLA4;
E3. Prior treatment with pazopanib;
E4. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
Note:
- Asymptomatic patients with treated CNS lesions are eligible.
- Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan;
E5. Patients using, or requirement to use while on the study, or not respecting the minimal wash-out period of medications listed below:
Forbidden concomitant medications and minimal wash-out period before Cycle 1 Day1
- Any approved anti-cancer systemic treatment including chemotherapy, hormonotherapy, biological therapy, or immunotherapy : 2 weeks
- Any investigational agents : 4 weeks
- Radiotherapy Note: palliative radiotherapy on non-target lesions is allowed. : 3 weeks
- Surgery
- Major surgical procedure, open biopsy, or significant traumatic injury : 4 weeks
- Abdominal surgery, abdominal interventions or significant abdominal traumatic injury : 60 days
- Live vaccines. Note: Influenza vaccination should be given during influenza season. Patients must not receive live attenuated influenza vaccine (e.g., FluMist®) : 4 weeks
- Systemic immunostimulatory agents, including but not limited to IFN-α, IFN-γ, or IL-2 : 4 weeks
- Immunosuppressive medication (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) with the exceptions of intranasal, inhaled, or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone (or 0.1mg/kg for pediatric patients), or an equivalent corticosteroid :2 weeks
- P-gp inhibitors : None
- Strong or moderate inhibitors of CYP3A4 : None
- Strong CYP3A4 inducers : None
- Oral or IV antibiotics :2 weeks
Note: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection, pneumocystis or chronic obstructive pulmonary disease exacerbation) are eligible.
E6. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
- patients with a history of autoimmune-related hypothyroidism who are on stable thyroid replacement hormone therapy,
- patients with controlled Type 1 diabetes mellitus,
-
patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are eligible provided that they meet the following conditions:
- Rash must cover less than 10% of body surface area (BSA).
- Disease is well controlled at baseline and only requiring low potency topical steroids.
- No acute exacerbations of underlying condition within the previous 12 months requiring psoralen plus ultraviolet A radiation (PUVA), methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids;
E7. Patients with HIV, active B or C hepatitis infection, or any other active infection.
E8. Patients with active tuberculosis;
E9. Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past;
E10. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan;
E11. Patients with a high-risk of hemorrhage or history of coagulopathy;
E12. Any contraindication to nivolumab, to ipilimumab or to pazopanib according to the Summary of Product Characteristics of each drug;
E13. History of other malignancy other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of disease for at least 3 years;
E14. Patient under tutorship or curatorship or deprived of liberty;
E15. Pregnant or breast-feeding woman
