A clinical trial to look at how well atezolizumab works when taken with other drugs, compared to atezolizumab alone, in people with urothelial cancer, after treatment with chemotherapy has not worked (MORPHEUS mUC)

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-based Treatment Combinations in Patients With Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Containing Chemotherapy (MORPHEUS mUC)

  • Bladder Cancer
Trial Status:

Recruiting

This trial runs in
Cities
  • Athens
  • Barcelona
  • Caen
  • Chaidari
  • Charlotte
  • Cleveland
  • Córdoba
  • L'Hospitalet de Llobregat
  • Lexington
  • London
  • Los Angeles
  • Louisville
  • Lyon
  • Madrid
  • Montpellier
  • Oxford
  • Pamplona
  • San Francisco
  • Santiago de Compostela
  • Seoul
  • Stanford
  • Sutton
  • Toulouse
  • València
Trial Identifier:

NCT03869190 WO39613

      Show trial locations

      The source of the below information is the publicly available website ClinicalTrials.gov. It has been summarised and edited into simpler language.

      The below information is taken directly from the publicly available website ClinicalTrials.gov within a week of any updates, and has not been edited.

      Results Disclaimer

      Trial Summary

      A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with MIBC and in participants with locally advanced or metastatic Urothelial Carcinoma (UC) who have progressed during or following a platinum-containing regimen. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population (e.g., with regard to prior anti-cancer treatment or biomarker status). Participants in the mUC Cohort who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen for Stage 2.

      Hoffmann-La Roche Sponsor
      Phase 1/Phase 2 Phase
      NCT03869190 , WO39613 Trial Identifier
      All Gender
      ≥18 Years Age
      No Healthy Volunteers

      How does the MORPHEUS mUC clinical trial work?
      This clinical trial is recruiting people who have a particular type of cancer called urothelial cancer. In order to take part, patients must have cancer that has spread to other parts of their bodies.

      The purpose of this clinical trial is to compare the effects, good or bad, of atezolizumab when taken with other drugs, compared to atezolizumab alone, in patients with locally advanced or metastatic urothelial cancer.  Patients who join this clinical trial will get either atezolizumab alone or atezolizumab with one of a selection of other drugs including enfortumab vedotin, niraparib, Hu5F9-G4, tocilizumab, linagliptin, or isatuximab.

      How do i take part in this clinical trial?
      To be able to take part in this clinical trial, you must have been diagnosed with urothelial cancer that has spread to other parts of your body. You must have already tried a specific type of chemotherapy, called platinum chemotherapy.

      You must not have previously been given any of the medicines being tested in this clinical trial and you cannot join the trial if you are pregnant or breastfeeding.

      If you think this clinical trial may be suitable for you and would like to take part, please talk to your doctor. If your doctor thinks that you might be able to take part in this clinical trial, he/she may refer you to the closest clinical trial doctor. They will give you all the information you need to make your decision about taking part in the clinical trial. You can also find the clinical trial locations on this page.

      You will have some further tests to make sure you will be able to take the treatments given in this clinical trial. Some of these tests or procedures may be part of your regular medical care. They may be done even if you do not take part in the clinical trial. If you have had some of the tests recently, they may not need to be done again.

      Before starting the clinical trial, you will be told about any risks and benefits of taking part in the trial. You will also be told what other treatments are available so that you may decide if you still want to take part.

      While taking part in the clinical trial, both men and women (if you are not currently pregnant but can become pregnant) will need to either not have heterosexual intercourse or take contraceptive medication for safety reasons. 

      What treatment will I be given if I join this clinical trial?
      Everyone who joins this clinical trial will be split into 7 groups randomly (like flipping a coin) and given either:

      • atezolizumab given as an infusion into your vein every 3 weeks
      • OR atezolizumab given as an infusion into your vein every 3 weeks and enfortumab vedotin given as an infusion into your vein on first and eighth day of each treatment round, which will be 3 weeks long
      • OR atezolizumab given as an infusion into your vein every 3 weeks and niraparib given as a tablet to swallow every day
      • OR atezolizumab given as an infusion into your vein every 2 weeks and Hu5F9-G4 given as an infusion into your vein every week for the first 2 months and then every 2 weeks after that
      • OR atezolizumab given as an infusion into your vein every 2 weeks and tocilizumab given as an infusion into your vein every 4 weeks
      • OR atezolizumab given as an infusion into your vein every 3 weeks and linagliptin given as a tablet to swallow every day
      • OR atezolizumab given as an infusion into your vein every 3 weeks and isatuximab given as an infusion into your vein every week for the first 3 weeks and then every 3 weeks after that.

      How often will I be seen in follow-up appointments, and for how long?
      You will be given the clinical trial treatment (atezolizumab alone or with another medicine) for as long as it can help you. You will be seen regularly by the clinical trial doctor every month. You are free to stop this treatment at any time. After being given your final treatment, you will still be seen by the clinical trial doctor within 1 month and then every 3 months after that. These hospital visits will include checks to see how you are responding to the treatment and any side effects that you may be having.

      What happens if I am unable to take part in this clinical trial?
      If this clinical trial is not suitable for you, you will not be able to take part. Your doctor will suggest other clinical trials that you may be able to take part in or other treatments that you can be given. You will not lose access to any of your regular care.

      For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03869190

      Trial-identifier: NCT03869190

      Trial Summary

      A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with MIBC and in participants with locally advanced or metastatic Urothelial Carcinoma (UC) who have progressed during or following a platinum-containing regimen. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population (e.g., with regard to prior anti-cancer treatment or biomarker status). Participants in the mUC Cohort who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen for Stage 2.

      Hoffmann-La Roche Sponsor
      Phase 1/Phase 2 Phase
      NCT03869190 , WO39613 Trial Identifier
      Atezolizumab, Enfortumab Vedotin, Niraparib, Hu5F9-G4, Tiragolumab, Sacituzumab Govitecan, Tocilizumab, Cisplatin, Gemcitabine Treatments
      Urothelial Carcinoma, Bladder Cancer Condition
      Official Title

      A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)

      Eligibility Criteria

      All Gender
      ≥18 Years Age
      No Healthy Volunteers
      Inclusion Criteria

      Inclusion Criteria for mUC Cohort:

      • Histologically documented, locally advanced or metastatic UC (also termed TCC or urothelial cell carcinoma of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
      • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing
      • Disease progression during or following treatment with no more than one platinum-containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence
      • ECOG Performance Status of 0 or 1
      • Measurable disease (at least one target lesion) according to RECIST v1.1
      • Adequate hematologic and end-organ function
      • Negative HIV test at screening
      • Negative total hepatitis B core antibody (HBcAb) test and hepatitis C virus (HCV) antibody at screening
      • Tumor accessible for biopsy
      • For women of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs
      • For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

      Inclusion Criteria for MIBC Cohorts:

      • ECOG PS of 0 or 1
      • Fit and planned-for cystectomy
      • Histologically documented MIBC (pT2-4, N0, M0), also termed TCC or urothelial cell carcinoma of the urinary bladder
      • N0 or M0 disease by CT or MRI
      • Adequate hematologic and end-organ function
      • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm
      • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
      Exclusion Criteria

      Exclusion Criteria for mUC Cohort:

      • Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
      • Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents, Trop-2 targeting agents, FAP-directed therapies, 4-1BB (CD137)-directed therapies, or topoisomerase 1 inhibitors
      • Treatment with investigational therapy within 28 days prior to initiation of study treatment
      • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
      • Eligibility only for the control arm
      • Prior allogeneic stem cell or solid organ transplantation
      • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
      • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment
      • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
      • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
      • Uncontrolled tumor-related pain
      • Uncontrolled or symptomatic hypercalcemia
      • Symptomatic, untreated, or actively progressing CNS metastases
      • History of leptomeningeal disease
      • Active or history of autoimmune disease or immune deficiency
      • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
      • History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
      • Active tuberculosis
      • Severe infection within 4 weeks prior to initiation of study treatment
      • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
      • Significant cardiovascular disease
      • Uncontrolled hypertension
      • Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment
      • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
      • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
      • Additional drug-specific exclusion criteria might apply

      Exclusion for MIBC Cohorts:

      • Prior treatment with systemic immunostimulatory agents prior to the initiation of study treatment
      • Eligibility only for the control arm
      • Prior allogeneic stem cell or solid organ transplantation
      • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment, with the following exceptions: Patients who received acute, low-dose, systemic immunosuppressant medications, or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor approval has been obtained. Patients who received mineralocorticoids, corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
      • Severe infection within 4 weeks prior to initiation of study treatment
      • Pregnancy or breastfeeding, or intention of becoming pregnant during the study

      Additional Exclusion Criteria for Atezo+Tira and Atezo (Atezolizumab) +Tira+Cis (Cisplatin)+Gem (Gemcitabine) in the MIBC Cohorts:

        - Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening.

      Additional Exclusion Criteria for the Cisplatin-Eligible MIBC Cohort:

      • Patients who decline neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate.
      • Impaired renal function.

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