Opdivo (Nivolumab) Demonstrates Nearly Doubled Disease-Free Survival as Adjuvant Therapy in Patients with High-Risk Muscle-Invasive Urothelial Carcinoma: Results from Phase III CheckMate -274 Trial

Shanghai, February 20219TOKYO /PRNewswire/ --Bristol-Myers Squibb China Announces Results from the Phase III Clinical Study CheckMate -274:Opdivo(Nivolumab) as adjuvant therapy for patients with high-risk muscle-invasive urothelial carcinoma after surgery has met the primary endpoint in both the overall randomized population and in patients with PD-L1 expression ≥1%, significantly improving disease-free survival (DFS). The CheckMate -274 study is the first Phase III clinical trial to evaluate immunotherapy as adjuvant treatment for muscle-invasive urothelial carcinoma and achieve positive results.

Among all randomized populations, receivingOpdivoThe median DFS in the treatment group [21.0 months] was nearly doubled compared with that in the placebo control group [10.9 months]; the risk was reduced by 30% (hazard ratio [HR] 0.70; 98.31% confidence interval [CI]: 0.54 to 0.89, p<0.001). In patients with PD-L1 expression ≥1%,Opdivoreducing the risk of disease recurrence or death by 47%,OpdivoThe median DFS for the treatment group and the placebo control group was not reached and 10.8 months, respectively (hazard ratio [HR] 0.53; 98.87% confidence interval [CI]: 0.34 to 0.84, p<0.001). The study data will be presented orally at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) on February 12, 2021, from 16:36 to 16:46 Eastern Standard Time (Abstract #391).

“Patients with muscle-invasive urothelial carcinoma typically require cystectomy to save their lives, yet approximately 50% still face postoperative recurrence,” said Dean Bajorin, MD, a genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center. “According to the CheckMate -274 clinical trial, patients treated with nivolumab had nearly twice the disease-free survival of those in the placebo group. These results are of significant clinical importance and have the potential to transform the current treatment paradigm for muscle-invasive urothelial carcinoma, addressing the urgent need for effective and well-tolerated postoperative therapies.”

In addition,OpdivoImprovements in efficacy were also demonstrated for key secondary endpoints, including non-urothelial recurrence-free survival (NUTRFS, defined as the time during which patients remain free of disease recurrence outside the bladder, ureter, or renal pelvis). In the overall randomized population,OpdivoThe median NUTRFS in treated patients exceeded two years [24.6 months], compared with 13.7 months in the placebo group (hazard ratio [HR] 0.72; 95% confidence interval [CI]: 0.58 to 0.89). In patients with PD-L1 expression ≥1%,OpdivoThe median NUTRFS for the treatment group and the placebo control group were not reached and 10.9 months, respectively (hazard ratio [HR] 0.54; 95% confidence interval [CI]: 0.38 to 0.77).

In this study,OpdivoThe safety profile is consistent with the safety profile previously reported in clinical studies of other solid tumors. ReceivedOpdivoThe proportions of patients experiencing treatment-related adverse events (TRAEs) in the treatment and placebo groups were 77.5% and 55.5%, respectively, with the incidence rates of Grade 3 or 4 TRAEs being 17.9% and 7.2%, respectively.

“By moving the application of immunotherapy to earlier stages of cancer, we will have the opportunity to intervene in the disease process, reduce tumor recurrence, and bring better treatment outcomes for patients,” said Dana Walker, M.D., Head of Genitourinary Oncology Development at Bristol-Myers Squibb, “withOpdivoThe adjuvant therapy regimen has not only demonstrated benefits in urothelial carcinoma but has also been confirmed to provide survival benefits for patients with early-stage melanoma, esophageal cancer, and lung cancer. We are delighted to see that the results of the CheckMate -274 study bring clinical benefits to cancer patients, and we extend our sincere gratitude to all the patients and researchers who participated in the trial. We look forward to collaborating with health authorities worldwide to make this treatment regimen accessible to more patients.”

AboutCheckMate-274

CheckMate-274 is a randomized, double-blind, multicenter Phase III clinical study designed to evaluateOpdivoTo compare the efficacy and safety versus placebo in patients with muscle-invasive urothelial carcinoma at high risk of recurrence after radical surgery. Patients were eligible regardless of whether they had received neoadjuvant therapy prior to surgery; receipt of cisplatin-based neoadjuvant therapy was a stratification factor. A total of 709 patients were randomized in a 1:1 ratio to receive either 240 mg every two weeks for up to one year or placebo.Opdivoor placebo treatment. The primary endpoints of the study were disease-free survival (DFS) in all randomized patients (i.e., the intent-to-treat population) and in patients with tumors expressing PD-L1 ≥1%. Key secondary endpoints included overall survival (OS), non-urothelial tract recurrence-free survival (NUTRFS), and disease-specific survival (DSS).

About Urothelial Carcinoma

Urothelial carcinoma typically originates in the bladder and is the tenth most common cancer worldwide, with approximately 550,000 new cases diagnosed annually. In addition to the bladder, urothelial carcinoma can arise in other parts of the urinary system, including the ureters and renal pelvis. Although most urothelial carcinomas are diagnosed at an early stage, the disease has high rates of recurrence and progression. More than 50% of patients with invasive urothelial carcinoma who undergo radical resection will experience disease recurrence postoperatively. Recurrence leads to a poor prognosis for patients with metastatic urothelial carcinoma, with a median overall survival of approximately 12–14 months following systemic therapy.

AboutOpdivo

OpdivoApproved in July 2014 as the world’s first PD-1 inhibitor, it has currently received approval in 66 countries and regions for a total of 11 tumor types [1], including lung cancer, head and neck cancer, gastric cancer, esophageal cancer, liver cancer, renal cell carcinoma, colorectal cancer, urothelial carcinoma, melanoma, Hodgkin lymphoma, and pleural tumors, benefiting more than 590,000 patients worldwide.

OpdivoIt is the first immuno-oncology drug approved for marketing in China. Currently, it has been approved for the following three indications in China; other indications have not yet been approved:

1) For the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK), and whose disease has progressed after or who are intolerant to prior platinum-based chemotherapy;

2) For patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have experienced disease progression during or after treatment with a platinum-containing regimen and whose tumors are PD-L1 positive (PD-L1-expressing tumor cells ≥1%);

3) For the treatment of patients with advanced or recurrent gastric or gastroesophageal junction adenocarcinoma who have previously received two or more systemic therapy regimens.

OpdivoIt is the only PD-1 inhibitor directly developed with the involvement of a Nobel Laureate in Physiology or Medicine. Bristol-Myers Squibb holds the exclusive rights to Dr. Tasuku Honjo’s PD-1 patent.

Note 1: Opdivo-based immunotherapy monotherapy and combination immunotherapy regimens