ONO PHARMACEUTICAL CO., LTD. (PRINCETON, NJ, November 18, 2015) - Bristol-Myers Squibb Company (NYSE:BMY) announced new long-term data of Opdivo in treatment-naïve BRAF wild-type advanced melanoma from CheckMate -066.
In USA, Opdivo was approved under accelerated approval for the treatment of unresectable or metastatic melanoma and disease progression following Yervoy and, if BRAF V600 mutation positive, a BRAF inhibitor in December 2014 and approved for the treatment of metastatic squamous NSCLC with progression on or after platinum-based chemotherapy in March 2015. Also, Opdivo in combination with Yervoy for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma received the approval in October 2015. Opdivo received expanded FDA approval in previously-treated metastatic non-small cell lung cancer in the same month. In EU, Opdivo was approved for the treatment of advanced (unresectable or metastatic) melanoma in adults regardless of BRAF status in June 2015.
European Commission approved Nivolumab BMS for the treatment of locally advanced or metastatic squamous NSCLC after prior chemotherapy in July 2015.
Also, BMS has a robust clinical development program in a variety of tumor types overseas, including: Renal Cell Carcinoma (RCC), Head and Neck Cancer, Blood Cancer, Glioblastoma, Colorectal Cancer, Pancreatic Cancer, Gastric Cancer, Hepatocellular Carcinoma, Triple-Negative Breast Cancer, Small- Cell Lung Cancer, Urothelial Cancer, etc. In Japan, ONO launched it for the treatment of unresectable melanoma in September 2014. Also, ONO is conducting clinical development programs including RCC, NSCLC, Head and Neck Cancer, Gastric Cancer, Esophageal Cancer, Hepatocellular Carcinoma, Hodgkin Lymphoma, Urothelial Cancer, Glioblastoma and Ovarian Cancer, etc.
Attached from the following page is the press release made by BMS for your information.
Contact
ONO PHARMACEUTICAL CO., LTD.
Corporate Communications public_relations@ono.co.jp
New Long-Term Data on Opdivo and the Opdivo + Yervoy Regimen Shows Survival Benefit Across Lines of Therapy in Advanced Melanoma
(PRINCETON, NJ, November 18, 2015) - Bristol-Myers Squibb Company (NYSE:BMY) today announced new long-term data of Opdivo in treatment-naïve BRAF wild-type advanced melanoma from CheckMate -066. In the trial, Opdivo continued to demonstrate superior overall survival versus dacarbazine with 57.7% of patients alive at two years compared to 26.7% of patients treated with dacarbazine. The safety profile of Opdivo was consistent with prior studies. The two-year survival and safety data from CheckMate -066 represent the longest follow-up from a randomized study of any PD-1 immune checkpoint inhibitor in the first-line setting of advanced melanoma. These data will be presented as a late-breaking presentation at the Society for Melanoma Research (SMR) 2015 International Congress in San Francisco, CA from November 18 to 21.
Bristol-Myers Squibb is also presenting updated data from various Phase 1 cohorts of Study 004 evaluating the Opdivo + Yervoy Regimen in patients with unresectable or metastatic melanoma, including up to three-year overall survival. The Phase 1b Study 004 is a dose-finding study on which the proof of concept for Opdivo + Yervoy Regimen approval was based.
'The long-term survival data for our Immuno-Oncology agent, Opdivo, as a single agent and in combination with Yervoy presented at SMR shows our continued commitment to improve outcomes for patients with advanced melanoma,' said Michael Giordano, M.D., senior vice president, head of Oncology Development, Bristol-Myers Squibb. 'The Opdivo + Yervoy Regimen has shown compelling potential for providing improved duration of response and long-term survival for some patients, and, as single agents, Opdivo and Yervoy continue to play a critical role as core components of the treatment continuum for advanced melanoma in appropriate patients.'
The global incidence of melanoma has been increasing over the past three decades, and despite recent advances in treatment, patients with advanced or metastatic disease often have a poor prognosis. Currently, five-year survival rates for advanced melanoma are between 5% and 19%.
Opdivo Associated with a Doubling of Overall Survival in CheckMate -066
CheckMate -066 is a Phase 3, randomized study which evaluated Opdivo as a single agent (n=210) versus dacarbazine (n=208) in patients with previously untreated, BRAF wild-type unresectable or metastatic melanoma. The primary endpoint of the trial was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).
In the trial, patients administered Opdivo demonstrated increased OS compared to dacarbazine.
With a minimum follow-up of 15.1 months, Opdivo continued to demonstrate significantly improved OS with the median OS not reached (NR) (95% CI: 23.1, NR) versus 11.2 months with dacarbazine (95% CI: 9.6, 13.0) (hazard ratio [HR]=0.43; 95% CI: 0.33, 0.57; p
and 57.7% for Opdivo and 46.3% and 26.7% for dacarbazine at 12 and 24 months, respectively. Subsequent treatment was used in 72.1% of patients in the dacarbazine arm, with 27 (13%) patients receiving Opdivo as the subsequent therapy. ORR and PFS also continued to be significantly greater with Opdivo. Objective response rate was 42.9% for Opdivo with 11% of patients achieving a complete
response, compared to a 14.4% ORR for dacarbazine with 1% of patients achieving a complete response. Of 90 responders, 81% experienced ongoing responses with Opdivo. Median PFS was 5.4 months for Opdivo versus 2.2 months for dacarbazine (HR=0.42; 95% CI: 0.32, 0.53; pOpdivo, respectively.
The safety profile of Opdivo in CheckMate -066 was consistent with prior studies and continued to be acceptable at two years. Incidences of treatment-related adverse events (AE) of any grade were similar between treatment arms, with Grade 3-4 AEs occurring in 13% and 17% of patients. Treatment- related select AEs reported in >10% of patients treated with Opdivo included pruritus (22%), diarrhea (18%) and rash (18%). Treatment-related AEs led to discontinuation in 6% of patients treated with Opdivo.
Opdivo + Yervoy Regimen Shows Improved Overall Survival Across Dosing Cohorts
Study 004 (CA209-004) is a Phase 1b, open-label, multicenter, multidose, dose-finding study of Opdivo in combination with Yervoy in patients with unresectable or metastatic melanoma. The trial evaluated different dosing schedules for the Opdivo + Yervoy Regimen, including Opdivo + Yervoy every three weeks for 12 weeks, followed by Opdivo every three weeks for 12 weeks (Cohorts 1, 2, 2a, and 3) (n=53), or Opdivo 1 mg/kg and Yervoy 3 mg/kg every three weeks for 12 weeks followed by Opdivo 3 mg/kg every two weeks (Cohort 8) (n=41). Forty percent of patients in Cohorts 1-3 and 51% of patients in Cohort 8 were previously treated.
For Cohorts 1-3, median duration of follow-up was 32.7 months (range 2.5 to 61.4). At 36 months (three years), the OS rate was 68% for patients in Cohorts 1-3 treated with the combination of Opdivo and Yervoy. Objective response rate was 42% with a 22.3 month median duration of response (95% CI: 12.09-NR). Complete responses were seen in 21% of patients in Cohorts 1-3. Rates of ongoing response were similar between Cohorts 1-3 and Cohort 8 (55% and 56%, respectively). These data represent the longest follow-up of the combination of Opdivo and Yervoy.
Patients included in Cohort 8 had poor prognostic factors at baseline, including ECOG performance status, history of brain metastases, prior systemic therapy and PD-L1 expression. At 18 months, 68% of patients were alive, with a median duration of follow-up of 19.9 months (range 0.9 to 24.0). Objective response rate was 44% with a median duration of response of 13.7 months (95% CI: 5.59-NR). Complete responses were seen in 17% of patients. In the study, high response rates and durable tumor response were observed in patients with or without poor prognostic factors at baseline.
The frequency of treatment-related AEs in the study were similar between Cohorts 1-3 and Cohort 8, and was consistent with the Phase 2 and 3 trials for the combination therapy. Across all concurrent cohorts, the incidence of treatment-related Grade 3-4 AEs was 56% and the incidence of treatment-related AEs leading to discontinuation was 27%.
About Opdivo
Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials - as monotherapy or in combination with other therapies - in which more than 8,000 patients have been enrolled worldwide. Opdivo is the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and currently has regulatory approval in more than 37 countries including the United States, Japan, and in the European Union.
About Yervoy
Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte- associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy 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, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor
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