Date: 2015-09-07
Type of
information: Presentation of results at a congress
phase: 3
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 a 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 (NSCLC)
Therapeutic
area: Cancer - Oncology
Country: Argentina, Australia, Austria, Canada, Chile, Czech Republic, France, Germany, Hungary, Ireland, Italy, Mexico, The Netherlands, Peru, Poland, Romania, Russian Federation, Spain, UK, USA
Trial
details:
- CheckMate -017 is a Phase 3, open-label, randomized study of Opdivo versus docetaxel in previously treated patients with advanced or metastatic squamous cell NSCLC. The trial randomized 272 patients to receive either nivolumab 3 mg/kg intravenously every two weeks or docetaxel 75 mg/m2 intravenously every three weeks. The primary endpoint is overall survival. Secondary endpoints include objective response rate and progression free survival. (NCT01642004)
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 -017 is a landmark Phase 3, open-label, randomized clinical trial that evaluated Opdivo (n=135) 3mg/kg intravenously over 60 minutes every two weeks versus standard of care, docetaxel (n=137) 75 mg/m2 intravenously administered every three weeks in patients with advanced SQ NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The study’s primary endpoint was OS and secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). The trial included patients regardless of their PD-L1 expression status. CheckMate -017 showed a doubling in 18 month OS benefit with an estimated 28% of patients alive at 18 months for Opdivo versus 13% for docetaxel. The median OS for the Opdivo arm was 9.2 months and 6.0 months for docetaxel (hazard ratio: 0.62 [95% CI, 0.48, 0.81; P = 0.0004]). In addition, Opdivo showed a statistically significant improvement in PFS and ORR. The PFS rate at 18 months was 17% for the Opdivo arm versus 2.7% for docetaxel. Median PFS was 3.5 months for patients administered Opdivo versus 2.8 months for docetaxel (hazard ratio: 0.63; [95% CI, 0.48, 0.83; P = 0.0008]). The ORR was 20% for the Opdivo arm versus 9% for docetaxel for an estimated odds ratio of 2.6 (95% CI, 1.3, 5.5; P = 0.0083), with an ongoing response seen in 63% of patients treated with Opdivo. In the trial, 28 patients were treated with Opdivo beyond initial progression, and nine demonstrated a non-conventional pattern of benefit (7%). The safety profile of Opdivo continued to be favorable versus docetaxel and treatment-related AEs occurred less frequently with Opdivo (n=131; any grade, 59%; grade 3–5, 8%; no grade 5 events) than docetaxel (n=129; any grade, 87%; grade 3–5, 58%), including both hematologic and non-hematologic toxicities. The majority of treatment-related select AEs in patients receiving Opdivo occurred within the first three months of treatment.
- • On January 11, 2015, BMS announced that an open-label, randomized Phase 3 study evaluating Opdivo® versus docetaxel in previously treated patients with advanced, squamous cell non-small cell lung cancer (NSCLC) was stopped early because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving Opdivo® compared to the control arm. The company will share these data – which for the first time indicate a survival advantage with an anti-PD1 immune checkpoint inhibitor in lung cancer – with health authorities. CheckMate -017 investigators are being informed of the decision to stop the comparative portion of the trial. BMS is working to ensure that eligible patients will be informed of the opportunity to continue or start treatment with Opdivo in an open-label extension as part of the company’s commitment to providing patient access to Opdivo®, and characterizing long-term survival. The company will complete a full evaluation of the final CheckMate -017 data and work with investigators on the future presentation and publication of the results.
Is
general: Yes
