A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)
Condition: Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell
Intervention: Avelumab (MSB0010718C); Axitinib (AG-013736)
Intervention description: Avelumab with two dose levels: 10 mg/kg IV and 5 mg/kg IV every two weeks to find the maximum tolerated dose in combination with axitinib and continue treatment in a dose expansion.; Axitinib with two dose levels: 5 mg and 3 mg oral BID to find the maximum tolerated dose in combination with avelumab and continue treatment in a dose expansion.
Intervention MeSH terms: Avelumab; Axitinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib

Summary:

      This is a Phase 1b, open-label, multi-center, multiple-dose trial designed to estimate the
      maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) of avelumab
      (MSB0010718C) in combination with axitinib (AG-013736). Once the MTD of avelumab administered
      in combination with axitinib is estimated (dose finding portion), the dose expansion phase
      will be opened to further characterize the combination in term of safety profile, anti tumor
      activity, pharmacokinetics, pharmacodynamics and biomarker modulation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed advanced RCC with clear cell component

          -  Primary tumor resected

          -  Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block
             from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a
             RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue
             block (not cut slides) from a primary or metastatic tumor resection or biopsy can be
             provided if the following criteria are met: 1) the biopsy or resection was performed
             within 1 year of enrollment AND 2) the patient has not received any intervening
             systemic anti-cancer treatment from the time the tissue was obtained and enrollment
             onto the current study. If an FFPE tissue block cannot be provided as per documented
             regulations,, 15 unstained slides (10 minimum) will be acceptable.

          -  Availability of an archival FFPE tumor tissue block from primary diagnosis specimen
             (if available and not provided per above). If an FFPE tissue block cannot be provided,
             15 unstained slides (10 minimum) will be acceptable

          -  At least one measureable lesion as defined by RECIST version 1.1 that has not been
             previously irradiated.

          -  Age ≥18 years (≥ 20 years in Japan).

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Adequate bone marrow function, renal and liver functions

        Exclusion Criteria:

          -  Prior systemic therapy directed at advanced RCC.

          -  Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has
             occurred during or within 12 months after the last dose of treatment

          -  Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, anti
             CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody
             (including ipilimumab), or any other antibody or drug specifically targeting T cell co
             stimulation or immune checkpoint pathways

          -  Prior therapy with axitinib as well as any prior therapies with other VEGF pathway
             inhibitors.

          -  Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any
             history of anaphylaxis.

          -  Any of the following in the previous 6 months: myocardial infarction, severe/unstable
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
             cerebrovascular accident, transient ischemic attack, deep vein thrombosis or
             symptomatic pulmonary embolism.

          -  Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for administration of inactivated vaccines (for example, inactivated
             influenza vaccines).