Ono Pharmaceutical Co., Ltd...announced that Ono Pharma Taiwan Co., Ltd. (“OPTW”), a Taiwanese subsidiary of ONO, received an additional approval for Opdivo® (nivolumab) Intravenous Infusion ("Opdivo"), a human anti-human PD-1 monoclonal antibody, on April 11 in Taiwan from the Taiwan Food and Drug Administration (TFDA) for the adjuvant treatment of patients with urothelial carcinoma at high risk of recurrence after radical resection....In this study, Opdivo showed a statistically significant improvement in disease-free survival (DFS), compared to placebo, both in all randomized patients and in patients whose tumor cells express PD-L1 ≥1%, the primary endpoints of the study. The safety profile of Opdivo in this study was consistent with previously reported studies with Opdivo in solid tumors.

Bristol Myers Squibb...announced that the European Commission (EC) has approved Opdivo (nivolumab) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection.

Ono Pharmaceutical Co...and Bristol-Myers Squibb K.K. (Tokyo, Japan; President, Jean-Christophe Barland) today announced that ONO has received a supplemental approval of Opdivo® (generic name: nivolumab) Intravenous Infusion (“Opdivo”), a human anti-human PD-1 monoclonal antibody, in Japan for the adjuvant treatment of urothelial carcinoma, for a partial change in approved items of the manufacturing and marketing approval....This approval is based on the results from the global multi-center, randomized, double-blind Phase 3 CheckMate -274 study (ONO-4538-33)...Opdivo showed a statistically significant improvement in disease-free survival (DFS), compared to placebo, both in all randomized patients and in patients whose tumor cells express PD-L1 ≥1%, the primary endpoints of the study.

In pts with TC<1% who also had CPS≥1, median DFS (95% CI) was 19.2 (16.1-25.6) months with NIVO vs. 10.4 (8.2-19.4) months with PBO; HR for NIVO v PBO in these pts was 0.79 (95% CI, 0.60-1.05)….With extended follow-up, this exploratory analysis of PD-L1 expression by CPS showed that most pts with TC<1% had CPS ≥1. In pts with TC<1% and CPS≥1, median DFS with NIVO was nearly double that with PBO.

We randomized a total of 709 patients 1:1 to nivolumab 240 mg or placebo every 2 wk intravenously for ≤1 yr of adjuvant treatment….patients with CPS ≥1 experienced improved DFS with nivolumab.

Bristol Myers Squibb (NYSE: BMY) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdivo (nivolumab) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection....The positive opinion is based on results from the Phase 3 CheckMate -274 study, which demonstrated a statistically significant and clinically meaningful increase in disease-free survival (DFS) with Opdivo compared to placebo in both all randomized patients and in patients whose tumor cells express PD-L1 ≥1%.

...high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more.

NIVO demonstrated a statistically significant and clinically meaningful improvement in DFS vs PBO for MIUC after radical surgery, both in ITT pts and pts with PD-L1 ≥ 1%.

...multicenter trial of NIVO vs PBO in pts with high-risk MIUC (bladder, ureter, or renal pelvis)...In total, 353 pts were randomized to NIVO (PD-L1 ≥ 1%, n = 140) and 356 pts to PBO (PD-L1 ≥ 1%, n = 142). The primary endpoint of DFS was met in ITT pts (median follow-up, 20.9 mo for NIVO; 19.5 mo for PBO) and in pts with PD-L1 ≥ 1%. DFS and NUTRFS were improved with NIVO vs PBO in both populations...NIVO demonstrated a statistically significant and clinically meaningful improvement in DFS vs PBO for MIUC after radical surgery, both in ITT pts and pts with PD-L1 ≥ 1%.

...CheckMate -274, a pivotal Phase 3 trial evaluating Opdivo (nivolumab) after surgery in patients with high-risk, muscle-invasive urothelial carcinoma, met its primary endpoints of improving disease free survival (DFS) versus placebo in both all randomized patients and in patients whose tumor cells express PD-L1 ≥1 (programmed death-ligand 1). CheckMate -274 is the first and only Phase 3 trial in which immunotherapy has reduced the risk of relapse in the adjuvant setting for these patients.The safety profile of Opdivo was consistent with previously reported studies in solid tumors.

...Overall Response Rate (ORR)`Metastasis-free Survival (MFS)`Overall Survival (OS)`Quality of Life (QOL) and Bladder Functioning Questionnaires Assessment`PD-1 and PDL-1 Expression Analysis Using Immunohistochemistry (IHC)`Th1/Th2 Cytokine Ratio Analysis...

...Disease Free Survival (DFS)`Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population...

...BIRC= blinded independent review committee PD-L1 expression level= membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells. ...

...Median Disease Free Survival by PD-L1 expression.`...

...PDL-1 combined positive score (CPS) was <1% in all non responders except one patient with CPS of 5%....Concurrent nivolumab and radiation therapy is tolerable and showed promising early efficacy in an elderly population with multiple comorbidities.

Confirmed objective response was achieved in 23 (28·4%, 95% CI 18·9–39·5) of the 81 patients with PD-L1 expression of 5% or greater, 29 (23·8%, 95% CI 16·5–32·3) of the 122 patients with PD-L1 expression of 1% or greater, and 23 (16·1%, 95% CI 10·5–23·1) of the 143 patients with PD-L1 expression of less than 1%...Nivolumab monotherapy provided meaningful clinical benefit.