First-Line Nivolumab/Ipilimumab Fails to Improve OS Vs Chemotherapy in PD-L1–Low Unresectable or Metastatic Urothelial Carcinoma

Patients with untreated unresectable or metastatic urothelial carcinoma and PD-L1 expression of 1% or more who received treatment with nivolumab and ipilimumab in the first-line setting did not experience an improved overall survival vs those getting standard-of-care chemotherapy, according to a final analysis of a phase 3 trial.

The phase 3 CheckMate901 trial (NCT03036098) assessing the use of first-line nivolumab (Opdivo) plus ipilimumab (Yervoy) vs standard-of-care chemotherapy in patients with untreated unresectable or metastatic urothelial carcinoma missed 1 of its primary end points of overall survival (OS) improvement in those with PD-L1 expression of 1% or more, according to a press release from Bristol Myers Squibb.

Data from the trial are still blinded. An independent monitoring committee recommended that the primary and secondary end points continue to be assessed. At the time of the analysis, no new safety findings were reported.

The combination is also being assessed in patients with cisplatin-ineligible unresectable or metastatic urothelial carcinoma. Moreover, a pivotal sub-study of CheckMate901 is assessing nivolumab and chemotherapy compared with chemotherapy alone in a cisplatin-ineligible population. Both investigations are ongoing.

“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,” Dana Walker, MD, MSCE, vice president and development program lead of genitourinary cancers at Bristol Myers Squibb, said in a press release. “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 primary trial enrolled a total of 707 patients who were randomized to receive either 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab every 3 weeks for 4 cycles then 480 mg of nivolumab every 4 weeks up to 2 years, or a gemcitabine-cisplatin– or gemcitabine-carboplatin–based chemotherapy regimen every 3 weeks for 6 cycles.

The study’s primary end points are OS in patients who are cisplatin-ineligible or who have a tumor PD-L1 expression of 1% or more as well as progression-free survival (PFS) in those who are cisplatin ineligible.Key secondary end points included OS in the overall patient population, PFS, and safety findings.

Nivolumab and ipilimumab combinations have yielded OS benefit in several phase 3 clinical trials across 5 tumor types, including non–small cell lung cancer, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma, and esophageal squamous cell carcinoma. Nivolumab has also demonstrated clinical benefit for patients with metastatic urothelial carcinoma and adjuvant muscle-invasive urothelial carcinoma in the second line.


Bristol Myers Squibb provides update on CheckMate -901 trial evaluating Opdivo (nivolumab) plus yervoy (ipilimumab) as first-line treatment for patients with unresectable or metastatic urothelial carcinoma. News release. Bristol Myers Squibb. May 16, 2022. Accessed May 16, 2022.