Frontline Nivolumab/Ipilimumab Misses OS End Point in PD-L1+ Unresectable or Metastatic Urothelial Carcinoma

The dual immunotherapy combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) was not found to significantly improve overall survival (OS) over standard-of-care chemotherapy when used in the first-line treatment of patients with unresectable or metastatic urothelial carcinoma with a PD-L1 expression of 1% or higher, missing the primary end point of the phase 3 CheckMate-901 trial (NCT03036098).¹

No new safety signals were observed with the regimen at the time of this analysis.

Moreover, an independent data monitoring committee has recommended that the trial continue to evaluate other primary and secondary end points. To date, Bristol Myers Squibb remains blinded to the findings.

“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 lead of genitourinary cancers at Bristol Myers Squibb, stated in a press release. “[Nivolumab] plus [ipilimumab] 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%.”

CheckMate-901 enrolled patients with unresectable or metastatic urothelial cancer who had an ECOG performance status of 0 or 1, and who did not receive prior systemic chemotherapy.²

Patients could not have disease that was suitable for local therapy delivered with curative intent, nor could they have any serious or uncontrolled medical disorder. Additionally, patients could not have previously received an anti–PD-1, anti–PD-L1, anti–PD-L2, anti-CD137, or anti–CTLA-4 antibody, or any other antibody or drug that targeted T-cell co-stimulation or checkpoint pathways.

A total of 707 patients were enrolled to the primary study. These patients were randomized to receive nivolumab at 1 mg/kg in combination with ipilimumab at 3 mg/kg every 3 weeks for 4 cycles, followed by nivolumab at 480 mg every 4 weeks for a maximum of 2 years, or chemotherapy comprised of gemcitabine/cisplatin or gemcitabine/carboplatin every 3 weeks for 6 cycles.

The primary end points of the study were OS in all patients who were ineligible for cisplatin-based chemotherapy and OS in patients with a PD-L1 expression of 1% or higher on tumor cells. Secondary end points included OS in all randomized patients, progression-free survival, and safety.

A sub-study of CheckMate-901 is examining nivolumab in combination with chemotherapy vs chemotherapy alone in patients who are candidates to receive cisplatin-based chemotherapy. The primary and sub-study are ongoing, and the company is slated to share data when they become available.

“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,” Walker added in the release.

References

1. 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. https://bit.ly/3MpjB90
2. Study of nivolumab in combination with ipilimumab or standard of care chemotherapy compared to the standard of care chemotherapy alone in treatment of patients with untreated inoperable or metastatic urothelial cancer (CheckMate901). ClinicalTrials.gov. Updated May 9, 2022. Accessed May 16, 2022. https://clinicaltrials.gov/ct2/show/NCT03036098