CA209-817 - Nivolumab and Ipilimumab in advanced malignancies
Research type
Research Study
Full title
A Phase IIIb/IV Safety Trial of Flat Dose Nivolumab in Combination with Ipilimumab in Participants with Advanced Malignancies
IRAS ID
213847
Contact name
Samreen Ahmed
Contact email
Sponsor organisation
Bristol-Myers Squibb International Corporation
Eudract number
2016-002621-10
Duration of Study in the UK
3 years, 10 months, 6 days
Research summary
Research Summary
Lung cancer is the second most common cancer in the UK and the most common cause of cancer related deaths in men and women. The most common form is non-small cell lung cancer (NSCLC). A significant number of NSCLC patients have advanced cancer at diagnosis, and unfortunately current standard treatment survival rate remains poor, with less than 5% of patients with advanced disease alive five years on from diagnosis.
This is a clinical trial of an immune therapy called nivolumab, combined with another immune therapy called ipilimumab. Nivolumab is a type of immunotherapy drug that is designed to stimulate the body’s own immune system to help attack cancer cells.
Nivolumab is already on the market in the UK for the treatment of advanced NSCLC and advanced renal cancer, both as a second treatment option after a first treatment has failed. Nivolumab is also already on the market in the UK for the treatment of advanced melanoma, a type of skin cancer, alone or in combination with ipilumumab. Ipilimumab alone is already on the market in the UK for the treatment of advanced melanoma.
Following a screening period, eligible patients will all receive nivolumab and ipilimumab in combination. Patients will receive the drugs until their cancer no longer responds or their doctor decides they should come out of the study. Patients will also stop if they are not tolerating the side effects.
Patients will undergo the following procedures during the study: tumour tissue biopsy (possible), CT/MRI scans, physical exams, check of vital signs and blood sampling for routine safety testing and study specific testing.
Patients will be treated by trained oncology teams in specialized NHS clinics. 500 patients are to be enrolled in the study with approximately 20 being treated in the UK. The study is sponsored by Bristol Myers Squibb.Summary of Results
1042 total subjects were screened and enrolled in a cohort: 391, 198, 396, and 57 in Cohorts A, A1, B, and C respectively. 412 subjects were screened but never assigned to a cohort, mostly due to no longer meeting the study criteria. All of these subjects were treated except for one (a subject from Cohort B who no longer met the eligibility criteria). No subjects were continuing in the treatment period at the time of study close. 7.6% to 21.2% of all treated subjects in each cohort completed the treatment period.
The safety data from 1041 subjects treated with nivolumab in CA209817 demonstrate that the safety profile of nivolumab 240 mg Q2W plus ipilimumab 1 mg/kg Q6W as 1L and 2L for NSCLC was manageable and consistent with the safety of nivolumab and ipilimumab across other studies using different dosing schedules and in different tumor types and/or disease settings of approved indications.
No new safety concerns were identified.
Most select AEs were Grade 1-2, and most were manageable using established treatment algorithms for early workup and intervention with immune-modulating medications (commonly systemic corticosteroids). Except for endocrine events, most select AEs and IMAEs were considered resolved at time of data cutoff. Abnormalities in hematology laboratory results, liver tests, kidney function tests, and electrolytes in nivolumab subjects were primarily Grade 1 or 2.
The safety profile of nivolumab 240 mg Q2W + ipilimumab 1 mg/kg Q6W was manageable in the treatment of advanced NSCLC. The incidences of high-grade drug-related AEs, select drug-related AEs, and IMAEs in all cohorts were consistent with the known profile of the nivolumab + ipilimumab combination and there were no new safety signals identified. Overall, the data from CA209817 indicate the safety of flat-dose nivolumab 240 mg Q2W + weight based ipilimumab 1 mg/kg Q6W was acceptable in the four cohorts. The efficacy of this combination was also encouraging, with durable responses observed across all cohorts and PD-L1 categories.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
16/WM/0473
Date of REC Opinion
13 Dec 2016
REC opinion
Further Information Favourable Opinion