Advanced, relapsed Clear Cell Renal Cell Carcinoma MedDRA version: 21.0 Level: LLT Classification code 10038396 Term: Renal carcinoma recurrent System Organ Class: 100000004864
Conditions
Interventions
Product Name: Spartalizumab
Product Code: PDR001
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Spartazilumab
Current Sponsor code: PDR001
Other descriptive name: PDR0
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For dose escalation and expansion arms on SA and combos, with the exception of Arm1B: 1. Male and female = 18 years of age 2. Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC). Disease must be measureable as determined by RECIST v1.1. 3. Patient with unresectable, locally advanced or metastatic ccRCC with documented disease progression following therapy with PD-1/L1 checkpoint inhibitor and a VEGF targeted therapy as monotherapy or in combination. Escalation: No restriction on the number of prior treatments Expansion: Up to 3 prior lines of treatment for advanced/metastatic disease 4. ECOG performance status = 1 For basket arm (Arm 1B): 1. Male and female of age = 12 years of age. 2. Histologically confirmed and documented malignancies in the context of the following cancer predisposing syndromes/disorders or harboring somatic mutations on one of these genes: • Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease) • Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma) • Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary paraganglioma and pheochromocytoma syndrome) • Malignancies with EPAS1/HIF2A mutations • Malignancies with ELOC/TCEB1 mutations 3. Patients must have either metastatic disease or locally advanced disease that is unresectable or that patients be unfit for resection or other treatment modalities. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, and have no available therapies of proven clinical benefit; or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy. 4. For patients age = 16 years: ECOG performance status = 1 For patients age = 12 and =65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but limited to surgery, radiation and/or corticosteroids. Patients with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment prior to study entry and at doses = 10 mg per day prednisone or equivalent for at least 2 weeks before administration of any study treatment. 2. History of seizure disorder and/or extrapyramidal symptoms. 3. Known additional malignancy that is progressing or requires active treatment within the past 3 year(s). Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or other tumors that will not affect life expectancy. 4. Patients having out of range lab values during screening and before the first dose of study treatment. Out of range lab values are defined as: 5. Absolute neutrophil count (ANC) 1.5 × ULN or creatinine clearance 1.5 × ULN , except for patients with Gilbert’s syndrome > 3.0 × ULN or direct bilirubin > 1.5 × ULN 10. Aspartate aminotransferase (AST) > 3 × ULN 11. Alanine aminotransferase (ALT) > 3 × ULN 12. Serum electrolytes = grade 2 despite adequate supplementation. 13. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes: 14. = 4 weeks for radiation therapy or limited field radiation for palliation within = 2 weeks prior to the first dose of study treatment. 15. = 4 weeks or = 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent. 16. = 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin C. 17. = 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists. 18. Patients who have undergone major surgery = 4 weeks prior to first dose of study treatment or who have not recovered for the surgical procedure. 19. 5. Patient previously treated with a HIF2alpha inhibitor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the safety and tolerability of DFF332 as a single agent and in combination with Everolimus, or Spartalizumab plus Taminadenant in patients with advanced ccRCC and HIF (hypoxia-inducible factor) stabilizing mutations.;Secondary Objective: To assess the preliminary anti-tumor activity of DFF332 as a single agent and in combination with Everolimus, or Spartalizumab plus Taminadenant. To characterize the PK of DFF332 as a single agent and in combination with Everolimus, or Spartalizumab plus Taminadenant.;Primary end point(s): • Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory parameters, vital signs and electrocardiograms (ECGs) • Tolerability: Dose interruptions, reductions and dose intensity for both dose escalation and expansion • Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 days) for DFF332 as a single agent and in combinations;Timepoint(s) of evaluation of this end point: At protocol define timepoints until End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall Response Rate (ORR), Best Overall Response (BOR), Progression Free Survival (PFS) (for RD only), Duration of Response (DOR) (for RD only), Disease Control Rate (DCR) per RECIST v1.1 • Plasma concentration of DFF332 and Taminadenant, whole blood concentration of Everolimus, serum concentration of Spartalizumab, and derived PK parameters for each analyte;Timepoint(s) of evaluation of this end point: At protocol define timepoints until End of study | — |
Countries
Belgium, Czechia, Czech Republic, France, Italy, Japan, Singapore, Spain, Taiwan, United States
Contacts
Public ContactTrial Monitoring Organization (TMo)
Novartis Farmacéutica S.A.
Outcome results
None listed