Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)

Recruiting

I'm Interested

Trial ID: NCT03869190

Purpose

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.

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)

Stanford Investigator(s)

Sumit Shah
Sumit Shah

Clinical Associate Professor, Medicine - Oncology

Eligibility


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.

Intervention(s):

drug: Atezolizumab

drug: Enfortumab Vedotin

drug: Niraparib

drug: Tiragolumab

drug: Sacituzumab Govitecan

drug: Tocilizumab

drug: Cisplatin

drug: Gemcitabine

drug: Magrolimab (Hu5F9-G4)

Recruiting

I'm Interested

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Aidan O'Brien
650-723-3046

New Trial Alerts

Receive email alerts when trials open to patients.