A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Cisplatin-Ineligible Patients with Locally Advanced or Metastatic Urothelial Carcinoma After Failure with Platinum Containing Chemotherapy (Morpheus-mUC)
- Conditions
- rothelial carcinoma (UC)MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004634-28-FR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 305
Stage 1
- Age >= 18 years
- Life expectancy >= 3 months, as determined by the investigator
- Histologically documented, locally advanced or metastatic UC (M1, Stage IV)
o Patients with mixed histologies are required to have a dominant transitional cell pattern
o Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera or bulky nodal
metastasis
- 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
Stage 1 and Stage 2
- Ability to comply with the study protocol, in the investigator's judgment
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days prior to Cycle (C) 1, Day (D) 1
- Negative HIV test at screening
- Negative total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL and negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test 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 as outlined for each specific treatment arm - For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
Stage 2
- Patients in the atezolizumab (Atezo) control arm: ability to initiate Stage 2 treatment within 3 months after loss of clinical benefit as
determined by the investigator while receiving control treatment Patients in an experimental arm during Stage 1: ability to initiate Stage 2
treatment within 3 months after experiencing unacceptable toxicity not related to Atezo or loss of clinical benefit as determined by the
investigator while receiving Stage 1 treatment
- Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 92
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 213
Stage 1
- Prior treatment with a T-cell co-stimulating therapy or an immune checkpoint inhibitor 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 any poly (ADP-ribose) polymerase inhibitor, nectin-4 targeting agents, signal regulatory protein a-targeting agents, or agents that block CD38
- Treatment with investigational therapy within 28 days prior to C1D1
- Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
- Eligible only for the control arm
Stage 1 and Stage 2
- Prior allogeneic stem cell or solid organ transplantation
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to the C1D1
- Treatment with systemic immunosuppressive medication within 2 weeks prior to C1D1, or anticipation of need for systemic immunosuppressant medication during study treatment
- Treatment with a live, attenuated vaccine within 4 weeks prior to C1D1, or anticipation of need for such a vaccine during Atezo treatment or within 5 months after the last dose of Atezo
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled tumor-related pain
- Uncontrolled or symptomatic hypercalcemia
- Symptomatic, untreated or actively progressing central nervous system metastases
- History of leptomeningeal disease
- Active or history of autoimmune disease, idiopathic pulmonary fibrosis, organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- History of malignancy other than UC within 2 years prior to screening
- Active tuberculosis (TB)
- Severe infection within 4 weeks prior to C1D1
- Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to C1D1
- Significant cardiovascular disease
- Grade >=3 hemorrhage or bleeding event within 28 days prior to C1D1
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to C1D1, or anticipation of need for a major surgical procedure during study
- Adverse events from prior anti-cancer therapy that have not improved to Grade <=1 or better
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug
- History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
- Known intolerance or hypersensitivity to any of the study drugs or their excipients and any of the drugs required for premedication
- Patients entering Stage 2: inability to tolerate Atezo during Stage 1
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study
For Atezo- enfortumab vedotin (EV) Arm during Stage 1 and Stage 2
- Ongoing sensory or motor neuropathy Grade >= 2
- Active keratitis or corneal ulcerations
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on Objective response rate;<br> Secondary Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on progression-free survival, overall survival, overall survival rate, duration of response, disease control<br> •To evaluate the safety of immunotherapy-based treatment combinations during Stage 1<br> •To characterize the pharmacokinetic (PK) profile of drugs that are administered as part of an immunotherapy based treatment combination during Stage 1<br> •To evaluate the immune response to drugs that are administered as part of an immunotherapy-based treatment combination during Stage 1<br> ;Primary end point(s): 1. Objective response rate;Timepoint(s) of evaluation of this end point: 1. Up to 5 years
- Secondary Outcome Measures
Name Time Method