Brief Title
Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)
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)
Brief 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Objective Response Rate (ORR) for mUC Cohort Stage 1
Secondary Outcome
Progression Free Survival (PFS) for mUC Cohort Stage 1
Condition
Urothelial Carcinoma
Intervention
Atezolizumab
Study Arms / Comparison Groups
Atezolizumab for mUC Cohort (Stage 1)
Description: Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
645
Start Date
June 1, 2019
Completion Date
November 27, 2027
Primary Completion Date
December 6, 2024
Eligibility 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
- Availability of TURBT specimen
- Negative HIV, HBcAb, and HCV test at screening
- 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 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
- Also includes all the mUC exclusion criteria
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 888-662-6728 (U.S. Only), [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT03869190
Organization ID
WO39613
Responsible Party
Sponsor
Study Sponsor
Hoffmann-La Roche
Collaborators
Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas
Study Sponsor
, ,
Verification Date
March 2023