Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)
- Conditions
- Urothelial CarcinomaBladder Cancer
- Registration Number
- NCT03869190
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 645
Inclusion Criteria for mUC Cohort:<br><br> - Histologically documented, locally advanced or metastatic UC (also termed TCC or<br> urothelial cell carcinoma of the urinary tract; including renal pelvis, ureters,<br> urinary bladder, and urethra)<br><br> - Availability of a representative tumor specimen that is suitable for determination<br> of PD-L1 and/or additional biomarker status by means of central testing<br><br> - Disease progression during or following treatment with no more than one<br> platinum-containing regimen for inoperable, locally advanced or metastatic UC or<br> disease recurrence<br><br> - ECOG Performance Status of 0 or 1<br><br> - Measurable disease (at least one target lesion) according to RECIST v1.1<br><br> - Adequate hematologic and end-organ function<br><br> - Negative HIV test at screening<br><br> - Negative total hepatitis B core antibody (HBcAb) test and hepatitis C virus (HCV)<br> antibody at screening<br><br> - Tumor accessible for biopsy<br><br> - For women of childbearing potential: agreement to remain abstinent or use<br> contraceptive measures and agreement to refrain from donating eggs<br><br> - For men: agreement to remain abstinent or use contraceptive measures, and agreement<br> to refrain from donating sperm<br><br>Inclusion Criteria for MIBC Cohorts:<br><br> - ECOG PS of 0 or 1<br><br> - Fit and planned-for cystectomy<br><br> - Histologically documented MIBC (pT2-4, N0, M0), also termed TCC or urothelial cell<br> carcinoma of the urinary bladder<br><br> - N0 or M0 disease by CT or MRI<br><br> - Adequate hematologic and end-organ function<br><br> - Availability of TURBT specimen<br><br> - Negative HIV, HBcAb, and HCV test at screening<br><br> - For women of childbearing potential: agreement to remain abstinent (refrain from<br> heterosexual intercourse) or use contraceptive measures and agreement to refrain<br> from donating eggs as outlined for each specific treatment arm<br><br> - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or<br> use contraceptive measures, and agreement to refrain from donating sperm, as<br> outlined for each specific treatment arm<br><br>Exclusion Criteria for mUC Cohort:<br><br> - Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4,<br> anti-PD-1, and anti-PD-L1 therapeutic antibodies<br><br> - Prior treatment with any of the protocol-specified study treatments including<br> treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP)<br> inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting<br> agents, or TIGIT-targeting agents, Trop-2 targeting agents, FAP-directed therapies,<br> 4-1BB (CD137)-directed therapies, or topoisomerase 1 inhibitors<br><br> - Treatment with investigational therapy within 28 days prior to initiation of study<br> treatment<br><br> - Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within<br> 3 weeks prior to initiation of study treatment<br><br> - Eligibility only for the control arm<br><br> - Prior allogeneic stem cell or solid organ transplantation<br><br> - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of<br> the drug (whichever is longer) prior to the initiation of study treatment<br><br> - Treatment with systemic immunosuppressive medication within 2 weeks prior to<br> initiation of study treatment or anticipation of need for systemic immunosuppressant<br> medication during study treatment<br><br> - Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of<br> study treatment, or anticipation of need for such a vaccine during atezolizumab<br> treatment or within 5 months after the last dose of atezolizumab<br><br> - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent<br> drainage procedures<br><br> - Uncontrolled tumor-related pain<br><br> - Uncontrolled or symptomatic hypercalcemia<br><br> - Symptomatic, untreated, or actively progressing CNS metastases<br><br> - History of leptomeningeal disease<br><br> - Active or history of autoimmune disease or immune deficiency<br><br> - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced<br> pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis<br><br> - History of malignancy other than UC within 2 years prior to screening, with the<br> exception of malignancies with a negligible risk of metastasis or death<br><br> - Active tuberculosis<br><br> - Severe infection within 4 weeks prior to initiation of study treatment<br><br> - Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation<br> of study treatment<br><br> - Significant cardiovascular disease<br><br> - Uncontrolled hypertension<br><br> - Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation<br> of study treatment<br><br> - Major surgical procedure, other than for diagnosis, within 4 weeks prior to<br> initiation of study treatment<br><br> - Pregnancy or breastfeeding, or intention of becoming pregnant during the study<br><br> - Additional drug-specific exclusion criteria might apply<br><br>Exclusion for MIBC Cohorts:<br><br> - Prior treatment with systemic immunostimulatory agents prior to the initiation of<br> study treatment<br><br> - Eligibility only for the control arm<br><br> - Prior allogeneic stem cell or solid organ transplantation<br><br> - Treatment with systemic immunosuppressive medication within 2 weeks prior to<br> initiation of study treatment, or anticipation of need for systemic<br> immunosuppressant medication during study treatment, with the following exceptions:<br> Patients who received acute, low-dose, systemic immunosuppressant medications, or a<br> one-time pulse dose of systemic immunosuppressant medication are eligible for the<br> study after Medical Monitor approval has been obtained. Patients who received<br> mineralocorticoids, corticosteroids for chronic obstructive pulmonary disease or<br> asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal<br> insufficiency are eligible for the study.<br><br> - Severe infection within 4 weeks prior to initiation of study treatment<br><br> - Pregnancy or breastfeeding, or intention of becoming pregnant during the study<br><br> - Also includes all the mUC exclusion criteria<br><br>Additional Exclusion Criteria for Atezo+Tira and Atezo (Atezolizumab) +Tira+Cis<br>(Cisplatin)+Gem (Gemcitabine) in the MIBC Cohorts:<br><br> - Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV<br> infection at screening.<br><br>Additional Exclusion Criteria for the Cisplatin-Eligible MIBC Cohort:<br><br> - Patients who decline neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant<br> cisplatin-based therapy is not appropriate.<br><br> - Impaired renal function.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) for mUC Cohort Stage 1;pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) for mUC Cohort Stage 1;Overall Survival (OS) for mUC Cohort Stage 1;Overall Survival (at specific time-points) for mUC Cohort Stage 1;Duration of Response (DOR) for mUC Cohort Stage 1;Disease Control Rate (DCR) for mUC Cohort Stage 1;Percentage of Participants with Adverse Events for mUC Cohort Stage 1;Serum Concentration of Atezolizumab for mUC Cohort Stage 2;Serum Concentration of Enfortumab Vedotin for mUC Cohort Stage 2;Serum Concentration of Sacituzumab Govitecan for mUC Cohort Stage 2;Presence of ADAs to Atezolizumab for mUC Cohort Stage 2;Percentage of Participants with Adverse Events for mUC Cohort Stage 2;Landmark Recurrence-Free Survival (RFS) for MIBC Cohorts;Landmark Event-Free Survival (EFS) for MIBC Cohorts;Landmark Overall Survival (OS) for MIBC Cohorts;Percentage of Participants with Adverse Events for MIBC Cohorts