Clinical Trial 18683

Cancer Type: Genitourinary
Interventions:Avelumab; MSB00100718C (Avelumab); Sunitinib Malate (SU011248); axitinib (AG-013736)

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Mayer Fishman

Overview

Study Title

A Phase 3, Multinational, Randomized, Open-Label, Parallel-Arm Study of Avelumab (MSB0010718C) in Combination with Axitenib (INLYTA®) Versus Sunitinub (SUTENT®) Monotherapy in the First-Line Treatment of Patients with Advanced Renal Cell Carcinoma

Summary

The main purpose of this study is to evaluate the effects of the study drug avelumab (MSB0010718C) in combination with axitinib (Inlyta®, AG 013736) and of sunitinib (Sutent®) alone to find out which is better for treating Advanced Renal Cell Cancer (aRCC).

Objective

2.1. Objectives - Primary Objective: To demonstrate that avelumab in combination with axitinib is superior to sunitinib monotherapy in prolonging PFS in the first-line treatment of patients with aRCC. Secondary Objectives: To compare avelumab in combination with axitinib to sunitinib monotherapy in the first-line treatment of patients with aRCC, with respect to overall survival. To evaluate other measures of efficacy of avelumab in combination with axitinib and sunitinib monotherapy in the first-line treatment of aRCC patients. To evaluate the overall safety profile of avelumab in combination with axitinib and sunitinib monotherapy in the first-line treatment of aRCC patients. To evaluate the population pharmacokinetics of avelumab and axitinib when administered in combination. To evaluate candidate predictive biomarkers in pre-treatment tumor tissue that may aid in the identification of a patient subpopulation most likely to benefit from treatment with avelumab in combination with axitinib and sunitinib monotherapy. To assess the immunogenicity of avelumab when combined with axitinib. To evaluate the effects of avelumab in combination with axitinib and sunitinib monotherapy on patient-reported outcomes. Exploratory Objectives: To explore the predictive and pharmacodynamic characteristics of peripheral blood and additional tumor tissue biomarkers that may be relevant to the mechanism of action of, or resistance to, avelumab in combination with axitinib and sunitinib monotherapy, including but not limited to biomarkers related to anti-tumor immune response or target modulation. To explore immune-related RECIST (irRECIST)-defined anti-tumor activity of avelumab in combination with axitinib and of sunitinib monotherapy in the first-line treatment of aRCC patients.

Inclusion Criteria

  • Histologically or cytologically confirmed advanced or metastatic Renal Cell Carcinoma (RCC) with clear cell component.
  • Availability of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a Response Evaluation Criteria in Solid Tumors (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 randomization AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and randomization onto the current study. If an FFPE tissue block cannot be provided as per documented regulations then, 15 unstained slides (10 minimum) will be acceptable.
  • Availability of an archival FFPE tumor tissue from primary tumor resection specimen (if not provided per above). If an FFPE tissue block cannot be provided as per documented regulations 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.
  • 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 or metastatic 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 and/or sunitinib as well as any prior therapies with other Vascular Endothelial Growth Factor (VEGF) pathway inhibitors.
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma Global Initiative for Asthma 2011).
  • 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).
  • Patients with newly diagnosed brain metastases or patients with known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.