Atezolizumab Plus Magrolimab, Niraparib, or Tocilizumab in Platinum-Refractory Metastatic Urothelial Carcinoma: A Phase Ib/II Open-Label, Randomized Umbrella Study.

Abstract

The MORPHEUS platform was designed to identify early efficacy signals and evaluate the safety of novel immunotherapy combinations across cancer types. The phase Ib/II MORPHEUS-UC trial (NCT03869190) is evaluating atezolizumab plus magrolimab, niraparib, or tocilizumab in platinum-refractory locally advanced or metastatic (mUC). Additional treatment combinations were evaluated and will be reported separately. Patients had locally advanced or mUC that progressed during or following treatment with a platinum-containing regimen. The primary efficacy endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoints included investigator-assessed progression-free survival (PFS) and overall survival (OS). Safety and exploratory biomarker analyses were also conducted. Seventy-six patients were randomized to receive either atezolizumab plus magrolimab (n=16), atezolizumab plus niraparib (n=15), atezolizumab plus tocilizumab (n=15), or atezolizumab monotherapy (control; n=30). No additive benefit in ORR, PFS, or OS was seen in the treatment arms versus the control. The best confirmed ORR was 26.7% with atezolizumab plus magrolimab, 6.7% with atezolizumab plus niraparib, 20.0% with atezolizumab plus tocilizumab, and 27.6% with atezolizumab monotherapy. Overall, the treatment combinations were tolerable and adverse events were consistent with each agent's known safety profile. Trends were observed for shrinkage of PD-L1+ tumors (atezolizumab, atezolizumab plus magrolimab, atezolizumab plus tocilizumab), inflamed tumors or tumors with high mutational burden (atezolizumab), and immune excluded tumors (atezolizumab plus magrolimab). The evaluated regimens in MORPHEUS-UC were tolerable. However, response rates for the combinations did not meet the criteria for further development in platinum-experienced locally advanced or mUC.