Trial results for a study investigating nivolumab in combination with ipilimumab or standard of care chemotherapy for untreated inoperable or metastatic urothelial cancer were posted on ClinicalTrials.gov on 2025-09-18. The study demonstrated that the nivolumab combination regimen improved median overall survival to 18.76 months in all randomized participants, compared to 14.32 months for standard of care chemotherapy alone, with a Hazard Ratio of 0.78 (p-value 0.0171).
Background
The study aimed to determine if nivolumab, either in combination with ipilimumab or with standard of care chemotherapy, is more effective than standard of care chemotherapy alone for participants with previously untreated inoperable or metastatic urothelial cancer.
Trial design
The study (NCT03036098) was a Phase 3 trial that enrolled 1314 participants with untreated inoperable or metastatic urothelial cancer. The trial compared nivolumab in combination with ipilimumab or standard of care chemotherapy (which included gemcitabine, cisplatin, and carboplatin) against standard of care chemotherapy alone. The purpose was to evaluate the efficacy of the investigational immunotherapy combinations.
Key results
The trial results showed improvements in overall survival (OS) across several participant groups. For "Overall Survival (OS) in All Randomized Participants for Primary Study":
- Median OS for Treatment 1 (nivolumab combination) was 18.76 Months.
- Median OS for Treatment 2 (standard of care chemotherapy alone) was 14.32 Months.
A Log Rank analysis for this outcome yielded a Hazard Ratio (HR) of 0.78 (95.0% CI: 0.63 to 0.96) with a p-value of 0.0171.
In "Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study":
- Median OS for Treatment 1 was 19.06 Months.
- Median OS for Treatment 2 was 13.21 Months.
A Log Rank analysis for this subgroup showed a Hazard Ratio (HR) of 0.79 (95.0% CI: 0.64 to 0.97) with a p-value of 0.0032.
For "Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study":
- Median OS for Treatment 1 was 16.30 Months.
- Median OS for Treatment 2 was 14.36 Months.
A Log Rank analysis for this PD-L1 positive subgroup showed a Hazard Ratio (HR) of 0.72 (95.0% CI: 0.59 to 0.88) with a p-value of 0.0018.
Regarding Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1]:
- In Cisplatin-ineligible Randomized Participants: Treatment 1 had a median PFS of 5.29 Months, while Treatment 2 had 5.88 Months.
- In PD-L1 Positive (≥ 1%) Participants: Treatment 1 had a median PFS of 5.39 Months, while Treatment 2 had 5.78 Months.
- In All Randomized Participants: Treatment 1 had a median PFS of 5.03 Months, while Treatment 2 had 6.01 Months.
What this means
The results from this Phase 3 study suggest that treatment with nivolumab in combination with either ipilimumab or standard of care chemotherapy offers a survival benefit for patients with previously untreated inoperable or metastatic urothelial cancer. The consistent improvement in median overall survival across the overall study population, as well as in cisplatin-ineligible and PD-L1 positive subgroups, indicates a potential new therapeutic option for this patient population. While progression-free survival outcomes were mixed, the overall survival data provides a meaningful clinical endpoint for consideration.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03036098, titled "Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Participants With Untreated Inoperable or Metastatic Urothelial Cancer," were posted on 2025-09-18 on clinicaltrials.gov.