Registration: ClinicalTrials.gov
Last updated: January 25, 2016
Main ID: NCT02659059
Registration Date: January 15, 2016
Main sponsor: Bristol-Myers Squibb
Open topic: Nivolumab plus Ipilimumab as a first-line treatment for stage IV non-small cell lung cancer checkpoint 568
Scientific topic: An open label, single-arm phase II study Nivolumab combined with Ipilimumab as first-line treatment for stage IV non-small cell lung cancer (NSCLC)
Date of first recruitment: February 2016
Target sample size: 170
Recruitment status: recruiting
Type of study: intervention
Study Design: Endpoint Classification: Safety / Efficiency Study, Intervention Model: Single Group Task, Masking: Open Label, Main Purpose: Treatment
Staging: Phase II
Recruiting countries:
United States
Key entry and exclusion criteria:
For more information about Bristol-Myers Squibb (BMS) clinical trial participation, please visit www.BMSSstudyConnect.com
Entry criteria:
- Male or female 18 years old or older
- Diagnosis of stage IV non-small cell lung cancer
- The diagnosis of relapsed stage IIIB non-small cell lung cancer and previous combination therapy with radiotherapy and chemotherapy failed treatment without further therapeutic options.
Exclusion criteria:
- Study subjects with incurable CNS metastases from the central nervous system are excluded
- Subjects with cancerous meningitis
- Subject has active, known, or suspected autoimmune diseases
- Study patients with diseases that require systemic treatment including the need for corticosteroids (> 10 mg equivalent of prednisone per day) or use other immunosuppressive drugs within 14 days of the first treatment
- Women who were pregnant or about to become pregnant before the treatment plan began, and / or were breastfed during the study.
- The inclusion / exclusion defined by other schemes can be applied by the standard.
Minimum age limit: 18 years old
Maximum age limit: None
Gender: gender
Intervention:
Biologics: Nivolumab (Opdivo) + Ipilimumab (Yervoy)
Main results:
Objective Response Rate (ORR) [Time Range: 6 months after the last patient ’s first treatment]
Secondary results:
Response duration (DOR) [Time frame: last patient 6 months after first treatment]
Progression-free survival (PFS) [Time frame: last patient 6 months after first treatment]
6-month progression-free survival (PFS) [Time frame: 6 months after the first dose]
Nivolumab (Opdivo) nivolumab: The FDA approved nivolumab on March 4, 2015 for the treatment of metastatic squamous non-small cell lung cancer with disease progression during or after platinum-based chemotherapy. Previously (in December 2014), the FDA accelerated approval of nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma who did not respond to other drugs. Nivolumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1, PD-L2, thus releasing the PD-1 pathway-mediated suppression of the immune response, including anti- Tumor immune response. Two studies establish FDA approval. The FDA approval is based on the results of an open-label, multi-center, multi-country randomized trial comparing the efficacy of nivolumab and docetaxel. The study targeted patients with metastatic squamous non-small cell lung cancer. These patients experienced disease progression during or after platinum-based chemotherapy. Patients were randomly assigned to receive nivolumab intravenously 3 mg / kg every 2 weeks (n = 135), or docetaxel 75 mg / m2 intravenously every 3 weeks (n = 137). The primary study endpoint was OS.
The effectiveness of Nivolumab on squamous NSCLC was further confirmed in a single-arm trial involving 117 cases of squamous non-small cell lung cancer. Participants in this study all experienced disease progression after undergoing platinum-based therapy and at least another systemic treatment regimen. In the cohort, 15% of patients had a total response, of which 59% had a response time of 6 months or more.
The efficacy of Nivolumab in the treatment of squamous NSCLC was confirmed in a randomized clinical study involving 272 patients, of which 135 patients received nivolumab and 137 patients received docetaxel. The primary endpoint of the study was overall survival, and it was found that nivolumab prolonged the overall survival by an average of 3.2 months compared to docetaxel. Another one-arm study involving 117 patients undergoing platinum-based chemotherapy and at least one systemic therapy for patients with advanced lung cancer further confirmed the safety and efficacy of nivolumab. The primary endpoints of the study were the objective response rate (ORR) and the proportion of patients with locally reduced or disappeared tumors. The results showed that 15% of patients produced an objective response, and 59% of patients maintained an objective response for 6 months or longer.
Ipilimumab (Yervoy) Ipilimumab: CTLA-4 is a negative regulator of T lymphocytes, which can inhibit its activation. Ipilimumab binds to CTLA-4 and prevents the latter from interacting with its ligand (CD80 / CD86). Blocking CTLA-4 can increase T cell activation and proliferation. The effect of Ipilimumab on melanoma is indirect, possibly through the anti-tumor immune response mediated by T cells.
