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)

  • STATUS
    Recruiting
  • End date
    Nov 27, 2027
  • participants needed
    645
  • sponsor
    Hoffmann-La Roche
Updated on 25 October 2022
cancer
combinations
measurable disease
carcinoma
gemcitabine
atezolizumab
metastatic urothelial carcinoma
niraparib

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.

Details
Condition Urothelial Carcinoma, Bladder Cancer
Treatment cisplatin, Gemcitabine, Tocilizumab, Atezolizumab, Hu5F9-G4, Niraparib, Linagliptin, Isatuximab, Sacituzumab govitecan, Enfortumab vedotin, RO7121661, Tiragolumab, RO7122290
Clinical Study IdentifierNCT03869190
SponsorHoffmann-La Roche
Last Modified on25 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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

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
Additional Exclusion Criteria for Atezo+Tira and Atezo (Atezolizumab) +Tira+Cis
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
(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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