Atezolizumab plus Magrolimab, Niraparib, or Tocilizumab versus Atezolizumab Monotherapy in Platinum-Refractory Metastatic Urothelial Carcinoma: A Phase Ib/II Open-Label, Multicenter, Randomized Umbrella Study (MORPHEUS Urothelial Carcinoma).
| Title: | Atezolizumab plus Magrolimab, Niraparib, or Tocilizumab versus Atezolizumab Monotherapy in Platinum-Refractory Metastatic Urothelial Carcinoma: A Phase Ib/II Open-Label, Multicenter, Randomized Umbrella Study (MORPHEUS Urothelial Carcinoma). |
|---|---|
| Authors: | Drakaki A; Division of Hematology and Oncology, UCLA David Geffen School of Medicine, Los Angeles, California.; Powles T; Barts Cancer Centre, Barts Health NHS Trust, Queen Mary University of London, London, United Kingdom.; Bamias A; National and Kapodistrian University of Athens, Athens, Greece.; Martin-Liberal J; Medical Oncology Department, Catalan Institute of Oncology (ICO) Hospitalet, Barcelona, Spain.; Shin SJ; Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.; Friedlander T; University of California San Francisco, Helen Diller Family Cancer Center, San Francisco, California.; Tosi D; Institut régional du Cancer de Montpellier (ICM), Montpellier, France.; Park C; Norton Cancer Institute, Louisville, Kentucky.; Gomez-Roca C; Department of Medical Oncology, Institut Claudius Regaud/IUCT Oncopole, Toulouse, France.; Joly Lobbedez F; Centre Francois-Baclesse, Medical Oncology, Caen, France.; Castellano D; Hospital 12 de Octubre, Madrid, Spain.; Morales-Barrera R; Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.; Moreno-Candilejo I; START Madrid Phase I Unit, Hospital Sanchinarro, Madrid, Spain.; Fléchon A; Centre Léon Bérard, Lyon, France.; Yuen K; Genentech, Inc., South San Francisco, California.; Rishipathak D; Genentech, Inc., South San Francisco, California.; DuPree K; Genentech, Inc., South San Francisco, California.; Young F; Roche Products Ltd, Welwyn Garden City, United Kingdom.; Michielin F; Roche Innovation Center Basel, Basel, Switzerland.; Shemesh CS; Genentech, Inc., South San Francisco, California.; Steinberg EE; Genentech, Inc., South San Francisco, California.; Williams P; Genentech, Inc., South San Francisco, California.; Lee JL; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. |
| Source: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Nov 01; Vol. 29 (21), pp. 4373-4384. |
| Publication Type: | Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Denville, NJ : American Association for Cancer Research, c1995- |
| MeSH Terms: | Carcinoma, Transitional Cell*/pathology ; Urologic Neoplasms*/pathology ; Urinary Bladder Neoplasms*; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Platinum/therapeutic use ; Humans ; Antibodies, Monoclonal, Humanized ; Indazoles ; Piperidines |
| Abstract: | Purpose: 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 urothelial carcinoma (mUC). Additional treatment combinations were evaluated and will be reported separately.; Patients and Methods: 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.; Results: 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 programmed death-ligand 1-positive tumors (atezolizumab, atezolizumab plus magrolimab, atezolizumab plus tocilizumab), inflamed tumors, or tumors with high mutational burden (atezolizumab), and immune excluded tumors (atezolizumab plus magrolimab).; Conclusions: 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.; (©2023 American Association for Cancer Research.) |
| Molecular Sequence: | ClinicalTrials.gov NCT03869190 |
| Substance Nomenclature: | 49DFR088MY (Platinum); 52CMI0WC3Y (atezolizumab); 0 (Antibodies, Monoclonal, Humanized); 90YIEHRFJ9 (magrolimab); HMC2H89N35 (niraparib); 0 (Indazoles); 0 (Piperidines); I031V2H011 (tocilizumab) |
| Entry Date(s): | Date Created: 20230831 Date Completed: 20231106 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.1158/1078-0432.CCR-23-0798 |
| PMID: | 37651261 |
| Database: | MEDLINE |
Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't