Date: 2017-04-03
Type of
information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: BMS (USA - NY)
Product: Opdivo® (nivolumab)+Yervoy® (ipilimumab)
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.
- Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses.
Disease: previously untreated advanced melanoma
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
- CheckMate -067 is a Phase 3, double-blind, randomized trial that evaluated the combination of Opdivo® plus Yervoy® or Opdivo® monotherapy versus Yervoy® monotherapy in 945 patients with previously untreated advanced melanoma. Patients in the combination group (n=314) received Opdivo® 1 mg/kg plus Yervoy® 3 mg/kg (Q3W) for four doses followed by Opdivo® 3 mg/kg every two weeks (Q2W). Patients in the Opdivo® monotherapy group (n=316) received Opdivo® 3 mg/kg Q2W plus placebo. Patients in the Yervoy® monotherapy group (n=315) received Yervoy 3 mg/kg every three weeks for four doses plus placebo. Patients were treated until progression or unacceptable toxic effects. OS and PFS were co-primary endpoints for the trial. Secondary endpoints included ORR, efficacy by tumor PD-L1 expression level and safety.
Latest
news:
- • On April 3, 2017, BMS announced the first overall survival (OS) data from the Phase 3 CheckMate -067 clinical trial. With a minimum follow-up of 28 months, the median OS had not yet been reached in either of the two Opdivo® treatment groups and was 20 months for the Yervoy® monotherapy group (95% CI: 17.1-24.6). Opdivo® in combination with Yervoy® and as a monotherapy reduced the risk of death 45% [hazard ratio (HR) 0.55; 95% CI: 0.42-0.72; P<0.0001] and 37% (HR 0.63; 95% CI: 0.48-0.81; P<0.0001), respectively, compared with Yervoy alone. The two-year OS rates were 64% for the Opdivo® plus Yervoy® combination, 59% for Opdivo® alone and 45% for Yervoy® alone. Results will be presented at the American Association for Cancer Research Meeting 2017 in Washington.
- The updated safety data reported in this new analysis were consistent with previously reported experience, with no cumulative toxicity noted or new safety signals identified. Grade 3/4 treatment-related adverse events occurred in 58%, 21%, and 28% of the combination, Opdivo® alone and Yervoy® alone groups, respectively.
- The proportion of patients experiencing complete responses (CR) compared to a previous 18 month follow-up analysis increased in the combination group to 17.2% from 12.1%, in the Opdivo alone group to 14.9% from 9.8%, and in the Yervoy alone group to 4.4% from 2.2%. Progression-free survival (PFS) and objective response rates (ORR) from updated analyses were both consistent with previous reports. The risk of disease progression was significantly reduced for both the combination and Opdivo monotherapy groups, 58% (HR 0.42; 95% CI: 0.34-0.51) and 46% (HR 0.54; 95% CI: 0.45-0.66), respectively, compared to Yervoy alone. The ORR for the two Opdivo groups, in combination and alone, and the Yervoy alone group was, respectively, 58.9% (95% CI: 53.3-64.4), 44.65% (95% CI: 39.1-50.3) and 19.0% (95% CI: 14.9-23.8).
Is
general: Yes
