May 16, 2022: “Bristol Myers Squibb announced the Phase 3 CheckMate -901 trial, comparing Opdivo (nivolumab) plus Yervoy (ipilimumab) to standard-of-care chemotherapy as a first-line treatment for patients with untreated unresectable or metastatic urothelial carcinoma, did not meet the primary endpoint of overall survival (OS) in patients whose tumor cells express PD-L1 ≥1% at final analysis.
The company remains blinded to the data, and an independent Data Monitoring Committee recommended that the trial continue to assess other primary and secondary endpoints.
No new safety signals were observed at the time of the analysis.
“Despite some progress in recent years, metastatic urothelial carcinoma remains a difficult disease to address, with a limited number of treatment options that can extend patients’ lives,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb.
“Opdivo plus Yervoy has demonstrated durable, long-term survival improvements in several challenging-to-treat advanced cancers, and we are disappointed that the final analysis of CheckMate -901 did not show this same benefit in urothelial carcinoma patients whose tumor cells express PD-L1 ≥1%.
We remain committed to advancing research in urothelial carcinoma, we look forward to seeing data from other parts of the CheckMate -901 trial, and we thank all of the patients, investigators and site personnel involved.”
The CheckMate -901 trial is also assessing Opdivo plus Yervoy in patients with unresectable or metastatic urothelial carcinoma who are ineligible for cisplatin-based chemotherapy.
Additionally, a sub-study of CheckMate -901 with pivotal intent is evaluating Opdivo in combination with chemotherapy versus chemotherapy alone in patients who are eligible for cisplatin-based chemotherapy.
The CheckMate -901 primary study and sub-study are ongoing, and the company will report results for these additional components of the study when available.
Opdivo plus Yervoy-based combinations have shown significant improvements in OS in six Phase 3 clinical trials in five tumors to date: non-small cell lung cancer, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma and esophageal squamous cell carcinoma.
In addition, Opdivo has shown clinical benefit in second-line metastatic urothelial carcinoma and adjuvant muscle-invasive urothelial carcinoma.
About CheckMate -901
CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy (primary study)or Opdivo in combination with chemotherapy (sub-study) compared to standard-of-care chemotherapy alone, in patients with untreated unresectable or metastatic urothelial cancer.
In the primary study, a total of 707 patients were randomized to receive either Opdivo (1 mg/kg) plus Yervoy (3 mg/kg) every three weeks for four cycles, followed by Opdivo (480 mg) every four weeks for a maximum of two years, or chemotherapy (gemcitabine-cisplatin or gemcitabine-carboplatin) every three weeks for six cycles.
The primary endpoints of the primary study are overall survival (OS) in patients who are ineligible for cisplatin-based chemotherapy and OS in patients with tumor cell PD-L1 expression ≥1%.
Key secondary endpoints include OS in all randomized patients, progression-free survival (PFS) and safety outcomes.
A sub-study of CheckMate -901 is evaluating Opdivo in combination with chemotherapy versus chemotherapy alone in patients who are eligible for cisplatin-based chemotherapy.
The OS outcomes for patients whose tumor cells express PD-L1 ≥1% are based on the final efficacy analysis for this endpoint of the CheckMate -901 primary study; the other parts of the study are ongoing.
About Urothelial Carcinoma
Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. 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 rates of recurrence and disease progression are high.
Approximately 50% of patients who undergo surgery will experience disease recurrence. Additionally, approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease.
For patients with metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy.
The poor durability of responses in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.”
