Description:
This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of avelumab
in combination with axitinib and of sunitinib monotherapy, administered as first-line
treatment, in patients with advanced renal cell carcinoma
Title
- Brief Title: A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)
- Official Title: A PHASE 3, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PARALLEL-ARM STUDY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AXITINIB (INLYTA(REGISTERED)) VERSUS SUNITINIB (SUTENT(REGISTERED)) MONOTHERAPY IN THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED RENAL CELL CARCINOMA
Clinical Trial IDs
- ORG STUDY ID:
B9991003
- SECONDARY ID:
2015-002429-20
- SECONDARY ID:
JAVELIN RENAL 101
- NCT ID:
NCT02684006
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Avelumab (MSB0010718C) | | Avelumab in combination with axitinib |
Axitinib (AG-013736) | Inlyta | Avelumab in combination with axitinib |
Sunitinib | Sutent | Sunitinib |
Purpose
This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of avelumab
in combination with axitinib and of sunitinib monotherapy, administered as first-line
treatment, in patients with advanced renal cell carcinoma
Trial Arms
Name | Type | Description | Interventions |
---|
Avelumab in combination with axitinib | Experimental | Avelumab administered at 10 mg/kg IV every two weeks in combination with axitinib, 5 mg PO BID. | - Avelumab (MSB0010718C)
- Axitinib (AG-013736)
|
Sunitinib | Active Comparator | Sunitinib given at 50 mg PO QD on schedule 4/2 | |
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed advanced or metastatic 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 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 providedas 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
VEGF pathway inhibitors
- Newly dignosed or active brain metastasis
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially
controlled asthma Global Initiative for Asthma 2011)
- Any of the following in the previous 12 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular
accident, transient ischemic attack
- Any of the following in the previous 6 months: 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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression Free Survival (PFS) in PD-L1 positive patients |
Time Frame: | From randomization up to 40 months. |
Safety Issue: | |
Description: | Progression Free Survival (PFS) is the time from randomization to date of first documentation of objective progression of disease assessed by BICR (by RECIST version 1.1) or death due to any cause. |
Secondary Outcome Measures
Measure: | Overall Survival (OS) in unselected patients |
Time Frame: | Every 3 months up to 8 years |
Safety Issue: | |
Description: | OS is the time from date of randomization to date of death due to any cause. |
Measure: | Number of participants with Objective Response (OR) |
Time Frame: | Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization |
Safety Issue: | |
Description: | Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1 recorded from randomization until disease progression assessed by BICR or death due to any cause) |
Measure: | Disease Control (DC) |
Time Frame: | Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization |
Safety Issue: | |
Description: | DC is defined as complete response (CR), partial response (PR), or stable disease (SD) according to the RECIST v.1.1 recorded from randomization until disease progression assessed by BICR or death due to any cause. |
Measure: | Time to Tumor Response (TTR) |
Time Frame: | Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization |
Safety Issue: | |
Description: | TRR is the time from randomization to first documentation of objective tumor response (CR or PR). |
Measure: | Duration of response (DR) |
Time Frame: | Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization |
Safety Issue: | |
Description: | DR is the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression assessed by BICR or death due to any cause |
Measure: | Progression Free Survival (PFS) by Investigator assessment |
Time Frame: | Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 months from randomization |
Safety Issue: | |
Description: | Progression Free Survival (PFS) is the time from randomization to date of first documentation of objective progression of disease assessed by the Investigator (by RECIST version 1.1) or death due to any cause. |
Measure: | Trough plasma concentration (Ctrough) of avelumab |
Time Frame: | Pre-dose |
Safety Issue: | |
Description: | Ctrough is defined as the concentration at the end of avelumab dosage interval |
Measure: | Trough plasma concentration (Ctrough) of axitinib |
Time Frame: | Pre-dose |
Safety Issue: | |
Description: | Ctrough is defined as the concentration at the end of axitinib dosage interval |
Measure: | Maximum plasma concentration (Cmax) of axitinib |
Time Frame: | 2 hours post-dose |
Safety Issue: | |
Description: | Cmax defined as the maximum plasma concentration of axitinib |
Measure: | Anti-Drug Antibody (ADA) levels of avelumab/Neutralizing antibodies titers for MSB0010718C |
Time Frame: | Pre-dose |
Safety Issue: | |
Description: | Immunogenicity assessment of avelumab |
Measure: | Tumor tissue biomarker status |
Time Frame: | Baseline |
Safety Issue: | |
Description: | Biomarker status defined as positive or negative based on a pre-specified scoring algorithm involving, for example, PD-L1 expression and/or quantitation of tumor infiltrating CD8+T lymphocytes as assessed by IHC |
Measure: | Overall Survival (OS) in biomarker-positive and biomarker-negative subgroups |
Time Frame: | Baseline |
Safety Issue: | |
Description: | OS in biomarker-negative and biomarker-positive subgroups. |
Measure: | Change From Baseline in FACT-Kidney Symptom Index (FKSI)-19 |
Time Frame: | Every 6 weeks up to 8 years |
Safety Issue: | |
Description: | The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains- Disease Related Symptoms (physical and emotional), Treatment related side effects and Functional and Well-Being . A negative change from Baseline represents a worsening of condition. |
Measure: | Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Health State Profile |
Time Frame: | Every 6 weeks up to 8 years |
Safety Issue: | |
Description: | EQ-5D Health State Profile: participant rated questionnaire to assess health-related quality of life in terms of a single index value. |
Measure: | Progression Free Survival (PFS) in biomarker-positive and biomarker-negative subgroups |
Time Frame: | Baseline |
Safety Issue: | |
Description: | PFS as measure of clinical outcome in biomarker-negative and biomarker-positive subgroups. |
Measure: | Objective Response (OR) in biomarker-positive and biomarker-negative subgroups |
Time Frame: | Baseline |
Safety Issue: | |
Description: | OR in biomarker-negative and biomarker-positive subgroups |
Measure: | Disease Control (DC) in biomarker-positive and biomarker-negative subgroups |
Time Frame: | Baseline |
Safety Issue: | |
Description: | DC in biomarker-negative and biomarker-positive subgroups |
Measure: | Time To Response (TTR) in biomarker-positive and biomarker-negative subgroups |
Time Frame: | Baseline |
Safety Issue: | |
Description: | TTR in biomarker-negative and biomarker-positive subgroups. |
Measure: | Duration of Response (DR) in biomarker-positive and biomarker-negative subgroups |
Time Frame: | Baseline |
Safety Issue: | |
Description: | DR in biomarker-negative and biomarker-positive subgroups. |
Measure: | Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Visual Analogic Scale |
Time Frame: | Every 6 weeks up to 8 years |
Safety Issue: | |
Description: | EQ-5D Visual Analogic Scale:patients rated their overall health status from 0 (worst imaginable heath state) to 100 (best imaginable heath state). |
Measure: | Time to treatment discontinuation/failure due to toxicity (TTF) |
Time Frame: | From Cycle 1 Day 1, every 6 weeks up to the End of Treatment |
Safety Issue: | |
Description: | TTF is defined as the time from Cycle 1 Day 1 to the date of the first documentation of discontinuation due to an adverse event or death due to study treatment toxicity |
Measure: | Treatment discontinuation/failure due to toxicity |
Time Frame: | From Cycle 1 Day 1, every 6 weeks up to the End of Treatment |
Safety Issue: | |
Description: | Treatment discontinuation is the percentage of patients who discontinue the treatment due to an adverse event or death due to study treatment toxicity |
Measure: | PFS on next-line therapy (PFS2) |
Time Frame: | From randomization up to 8 years. |
Safety Issue: | |
Description: | PFS2 is defined as the time from randomization to discontinuation of next line treatment, second objective disease progression, or death from any cause, whichever occurs first. |
Measure: | Progression Free Survival (PFS) in unselected patients |
Time Frame: | From randomization up to 40 months. |
Safety Issue: | |
Description: | Progression Free Survival (PFS) is the time from randomization to date of first documentation of objective progression of disease assessed by BICR (by RECIST version 1.1) or death due to any cause. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Pfizer |
Trial Keywords
- Cancer
- renal cell cancer
- kidney disease
- kidney neoplasms
- axitinib, sunitinib
Last Updated
August 19, 2021