Clinical Trials

Date: 2015-09-07

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 16th World Conference on Lung Cancer

Company: BMS (USA - NY)

Product: Opdivo® (nivolumab)

Action mechanism:

• monoclonal antibody/immune checkpoint inhibitor. Nivolumab is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. PD-1, a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body. Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. Opdivo® is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes (i.e., the interaction of PD-1 with its ligands PD-L1 and PD-L2), thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them. Opdivo® is the world’s first approved drug targeting PD-1.
• This monoclonal antibody has been generated under a research collaboration entered into in May 2005 between Ono and Medarex. When Medarex was acquired by BMS in 2009, it also granted BMS its rights to develop and commercialize the anti-human PD-1 monoclonal antibody in North America. Through the collaboration agreement entered into in September 2011 between Ono and BMS, Ono granted BMS exclusive rights to develop and commercialize Opdivo® in the rest of the world, except in Japan, Korea and Taiwan where Ono has retained all rights to develop and commercialize the compound.

Disease: advanced squamous cell non-small cell lung cancer

Therapeutic area: Cancer - Oncology

Country: France, Germany, Italy, USA

Trial details:

• Checkmate -063 is a Phase 2 single arm, open-label study designed to assess advanced squamous cell NSCLC patients who progressed after both platinum-based therapy and at least one additional systemic therapy with an ECOG Performance Status of 0 or 1 who were treated with Opdivo as a single agent 3mg/kg by intravenous infusion every two weeks until disease progression or treatment discontinuation (n=117). The primary endpoint was ORR as assessed by an IRC using RECIST 1.1 criteria. Responders were further characterized by duration of response. Secondary endpoints included investigator-assessed ORR. Overall survival, PFS and efficacy by PD-L1 expression status were exploratory endpoints. All treated patients had received at least two prior systemic regimens with 65% receiving greater than or equal to three prior therapies. Seventy-six percent of patients were within three months of completion of their most recent therapy. The best response to the most recent prior systemic therapy was progressive disease in 61% of patients. (NCT01721759)

Latest news:

• • On September 7, 2015, BMS announced longer term survival and safety data from CheckMate -017 and -063, two pivotal trials evaluating Opdivo® in previously treated squamous (SQ) non-small cell lung cancer (NSCLC), showing sustained survival benefit across these studies. In both trials, Opdivo® showed an estimated 18 month overall survival (OS) rate of 27% (CheckMate -063) to 28% (CheckMate -017); survival benefit was independent of PD-L1 expression. The safety profile of Opdivo® is consistent with previously-reported trials, and in CheckMate -017, is also favorable compared to docetaxel. These data have been presented at the 16th World Conference on Lung Cancer (Abstract #736, CheckMate -017 and #828, CheckMate -063). Previously-reported one year results from CheckMate -017 showed a significantly superior OS rate of 42% versus 24% for docetaxel. In CheckMate -063, the estimated one-year survival rate was 39%. (see table below)

		CheckMate -017				CheckMate -063
		Nivolumab N = 135		Docetaxel N = 137		Nivolumab N = 117
1-Year Overall Survival		42%		24%		39%
18-Month Overall Survival		28%		13%		27%

• CheckMate -063 is a Phase 2, single-arm, open-label trial that included patients with metastatic SQ NSCLC who had progressed after receiving a platinum-based therapy and at least one additional systemic treatment regimen (n=117). In this trial, Opdivo showed an estimated 18-month OS rate of 27%. At 18 months, confirmed objective response rate, the study’s primary endpoint, was 15% (95% CI: 9, 22). Median OS was 8.1 months (95% CI: 6.1, 10.9). Most treatment-related AEs were of low grade (any grade, 75%; grade 3-4, 17%) and managed using established treatment algorithms.
• • On October 30, 2014, BMS announced results from CheckMate -063, a Phase 2 single-arm, open-label study of Opdivo® (nivolumab), an investigational PD-1 immune checkpoint inhibitor, administered as a single agent in patients with advanced squamous cell non-small cell lung cancer (NSCLC) who have progressed after at least two prior systemic treatments with 65% receiving three or more prior therapies (n=117). With approximately 11 months of minimum follow up, the objective response rate (ORR, the study’s primary endpoint) was 15% (95% CI = 8.7, 22.2) as assessed by an independent review committee (IRC) using RECIST 1.1 criteria and the median duration of response was not reached. The estimated one-year survival rate was 41% (95% CI = 31.6, 49.7) and median overall survival (mOS) was 8.2 months (95% CI = 6.05, 10.91). These data will be presented during the Plenary Session at the 2014 Chicago Multidisciplinary Symposium on Thoracic Oncology on October 31 (Abstract #3462).
• All treated patients had received at least two prior systemic regimens with 65% receiving greater than or equal to three prior therapies. Seventy-six percent of patients were within three months of completion of their most recent therapy. The best response to the most recent prior systemic therapy was progressive disease in 61% of patients. With approximately 11 months of minimum follow up, the ORR was 15% (95% CI = 8.7, 22.2) as assessed by an IRC using RECIST 1.1 criteria and the median duration of response was not reached. The estimated one-year survival rate was 41% (95% CI = 31.6, 49.7) and mOS was 8.2 months (95% CI = 6.05, 10.91). An additional 26% of patients had stable disease with a median duration of six months (95% CI, 4.73, 10.91) giving a disease control rate (defined as partial response + stable disease) of 41%. For patients with quantifiable PD-L1 expression, responses were observed independent of PD-L1 status.
• Grade 3-4 drug-related AEs were reported in 17.1% of patients. The most common (greater than or equal to 2%) Grade 3-4 AEs were fatigue (4.3%), pneumonitis (3.4%), and diarrhea (2.6%). Drug-related AEs generally were manageable with corticosteroids and/or supportive care as per established safety algorithms. Discontinuations due to drug-related AEs of any grade occurred in 12% of patients and there were two drug-related deaths in patients with muliple comorbidities and in the setting of progressive disease.

Is general: Yes