A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)

Pfizer

Status and phase

Completed

Phase 1

Conditions

Renal Cell Cancer

Treatments

Drug: Axitinib (AG-013736)

Drug: Avelumab (MSB0010718C)

Study type

Interventional

Funder types

Industry

Identifiers

NCT02493751

2015-001137-25 (EudraCT Number)

Javelin Renal 100 (Other Identifier)

B9991002

Details and patient eligibility

About

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.

Enrollment

55 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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).