PRINCETON, N.J. – Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Opdivo® (nivolumab), in combination with cisplatin and gemcitabine, for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC), the most common type of bladder cancer. This approval is based on results from the Phase 3 CheckMate –901 trial which evaluated Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy (n=304), compared to cisplatin-gemcitabine alone (n=304), for patients with previously untreated unresectable or metastatic UC. The primary efficacy endpoints were overall survival (OS) and progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR).
In the trial, with a median follow-up of approximately 33 months, treatment with Opdivo in combination with cisplatin and gemcitabine reduced the risk of death by 22%, demonstrating a median OS of 21.7 months versus 18.9 months with cisplatin-gemcitabine alone (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.63, 0.96; p=0.0171). Patients receiving Opdivo in combination with cisplatin and gemcitabine had their risk of disease progression or death reduced by 28%, with a median PFS of 7.9 months compared to 7.6 months with cisplatin-gemcitabine alone (HR 0.72; 95% CI: 0.59, 0.88; p=0.0012).
Additionally, in exploratory analyses, treatment with Opdivo in combination with cisplatin and gemcitabine resulted in an objective response rate (ORR) of 57.6% (n=175) (95% CI: 51.8, 63.2) versus 43.1% (n=131) (95% CI: 37.5, 48.9) with cisplatin-gemcitabine alone. The complete response (CR) rate and partial response (PR) rate seen in patients treated with Opdivo in combination with cisplatin and gemcitabine was 22% (n=66) and 36% (n=109), respectively, versus 12% (n=36) and 31% (n=95) with cisplatin-gemcitabine alone.1
“This approval marks an important advancement in a historically difficult-to-treat setting, where there has been a need for new and differentiated first-line approaches that may offer patients a chance to live longer,” said Guru P. Sonpavde, MD, Medical Director of Genitourinary Oncology and the Phase I Clinical Research Unit and Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute, Orlando, Florida. “Based on outcomes and the safety profile seen in the CheckMate -901 clinical trial, the approval of Opdivo in combination with cisplatin and gemcitabine has the potential to change how metastatic or unresectable UC is treated for certain patients and offers them new hope.”
Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials. Please see Important Safety Information below.
“Bringing Opdivo to the first-line setting in UC with chemotherapy is the latest realization of our history of research and progress in immunotherapy, which has helped transform the treatment landscape for many cancers, including bladder cancer,” said Wendy Short Bartie, senior vice president and general manager, U.S. Hematology and Oncology at Bristol Myers Squibb. “This milestone adds a meaningful expansion to our portfolio of Opdivo-based treatments in genitourinary cancers, where we now have offerings in UC spanning three indications across stages of disease and treatment needs.”
The FDA previously approved Opdivo for the adjuvant treatment of adult patients with UC who are at high risk of recurrence after undergoing radical resection of UC; it also previously approved Opdivo for the treatment of adult patients with locally advanced or metastatic UC who have had disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Bristol Myers Squibb’s supplemental Biologics License Application (sBLA) leading to today’s approval was granted Priority Review status by the FDA, and was approved under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible. The review was also conducted under the FDA’s Project Orbis initiative, which enables concurrent review by the health authorities in several other countries where the application remains under review.
About CheckMate -901
CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to cisplatin-gemcitabine alone, in patients with previously untreated unresectable or metastatic urothelial cancer.
In the CheckMate -901 study, a total of 608 cisplatin-eligible patients were randomized to receive either Opdivo 360 mg in combination with cisplatin-gemcitabine every three weeks for up to six cycles followed by Opdivo monotherapy 480 mg every 4 weeks until disease progression or unacceptable toxicity up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study were overall survival (OS) and progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR). The OS and PFS outcomes for cisplatin-eligible patients are based on the final efficacy analyses of these endpoints.
Select Safety Profile from CheckMate -901
Serious adverse reactions occurred in 48% of patients receiving Opdivo with chemotherapy.1 The most frequent serious adverse reactions reported in ≥2% of patients who received Opdivo with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%). The most common adverse reactions (reported in ≥20% of patients) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy. Fatal adverse reactions occurred in 3.6% patients who received Opdivo with chemotherapy; these included sepsis (1%). Opdivo and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction.
About Urothelial Carcinoma
Bladder cancer is the sixth most common cancer in the U.S., with an estimated 83,190 new cases expected to be diagnosed in 2024. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo radical surgery will experience disease progression and recurrence, generally within two years post-surgery. Approximately 20% to 25% of patients with urothelial carcinoma present with metastatic disease, and treatment challenges have historically persisted in the first- and second-line settings, in part due to limited therapeutic options.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.
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