A Phase 2 Dose-Ranging Study of BMS-936558 (MDX-1106) In Subjects With Advanced/Metastatic Clear-Cell Renal Cell Carcinoma

• Register: EUCTR
• Last refreshed on: 18 January 2016
• Main ID: EUCTR2011-002957-67-IT
• Date of registration: 16/12/2011
• Prospective Registration: No
• Primary sponsor: BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
• Public title: A Phase 2 Dose-Ranging Study of BMS-936558 (MDX-1106) In Subjects With Advanced/Metastatic Clear-Cell Renal Cell Carcinoma
• Scientific title: A Randomized, Blinded, Phase 2 Dose-Ranging Study of BMS-936558 (MDX-1106) in Subjects With Progressive Advanced/Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy Revised Protocol 01 incorporating Administrative Letter 01 and Amendment 02
• Date of first enrolment: 28/11/2011
• Target sample size: 181
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002957-67
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: dose-ranging Number of treatment arms in the trial: 3

Countries of recruitment

Canada, Finland, Italy, United States

Contacts

• Name: EU Study Start-Up Unit
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: EU Study Start-Up Unit
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
Histologic confirmation of RCC with a clear cell component. • Previous treatment with at least one anti-angiogenic agent • Progressed within 6 months of study enrollment • Subjects should not have had more than 3 prior treatments for locally advanced or metastatic disease. • Must have available tumor tissue for submission • Subjects must also meet various laboratory parameters for inclusion (see Protocol section 3.3.1 item 4)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 136
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion criteria:
• Active CNS metastases within 30 days of study enrollment • Subjects with any active autoimmune disease or a history of known autoimmune disease • Subjects with uncontrolled adrenal insufficiency • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Advanced/Metastatic renal cell carcinoma with a clear cell
MedDRA version: 14.1 Level: PT Classification code 10038410 Term: Renal cell carcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Code: BMS-936558
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: BMS-936558-01
Other descriptive name: Anti-PD-1 Human Monoclonal Antibody; MDX-1106
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To evaluate the dose response relationship in the 0.3, 2, and 10 mg/kg BMS-936558 arms as measured by Progression-free survival (PFS).

Primary end point(s): Progression free survival as measured by tumor assessments (radiographic scans) and the collection of death data. It will be compared to the doses given across the 3 treatment arms to see if a dose response exists.

Secondary Objective: To estimate PFS in the BMS-936558 arms • To estimate the response rate in the BMS-936558 arms • To estimate the Overall Survival (OS) in the BMS-936558 arms • To estimate the rate of adverse events in the BMS-936558 arms + Exploratory Objectives: • To evaluate changes in QTc in each treatment arm • To estimate the immune-related response rate (irRR) and irPFS in the 2 and 10 mg/kg BMS-936558 arms relative to the 0.3 mg/kg arm • To explore associations between PD-L1 expression in tumors and other immune response biomarkers on clinical outcome • To characterize the pharmacokinetics of BMS-936558 and to explore exposure-safety and exposure-efficacy relationships.

Timepoint(s) of evaluation of this end point: Tumor assessments (radiographic scans) will be done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression is documented. Subjects will be assessed for survival every 3 months.

Secondary Outcome(s)

Secondary end point(s): • Progression free survival in the BMS-936558 arms • The tumor response rate in the BMS-936558 arms as assessed by the Investigator assessment of best overall response • The overall survival in the BMS-936558 arms as collected by death data.

Timepoint(s) of evaluation of this end point: • Progression free survival will be assessed in each individual treatment arm by tumor assessments every 6 weeks • The tumor response rate will be assessed on all subjects at the time they discontinue study treatment by the Investigators assessment of best overall response for a subject • The survival in each treatment arm will be assessed by the collection of death data every 3 months following the discontinuation of study therapy until a subjects death

Secondary ID(s)

CA209-010

NCT01354431

2011-002957-67-FI

Source(s) of Monetary Support

Bristol-Myers Squibb International Corporation