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Clinical Trial 19981

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT03513952

Phase: Phase II
Principal Investigator: Jain, Rohit

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or 1-800-679-0775 Learn More

Overview

Study Title

A Randomized Phase II Study of Atezolizumab (MPDL3280A) plus Recombinant Human IL-7 (CYT107) in patients with locally advanced or metastatic urothelial carcinoma

Summary

This phase II trial studies how well atezolizumab when given with glycosylated recombinant human interleukin-7 (CYT107) works in treating participants with urothelial carcinoma that has spread to nearby tissue or lymph nodes, cannot be removed by surgery, or has spread to other places in the body. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. CYT107 is a biological product naturally made by the body that may stimulate the immune system to destroy tumor cells. Giving atezolizumab and CYT107 may work better in treating participants with locally advanced, inoperable, or metastatic urothelial carcinoma

Objective

The goals of this trial are to evaluate the safety and tolerability of the investigational treatment combination, and to determine whether the addition of CYT107 to atezolizumab improves the objective response rate achieved by atezolizumab alone in patients with advanced/non-resectable bladder cancer who are either not considered to be eligible for cisplatin-based treatment or have recurrent disease after platinum chemotherapy. Primary Objectives To determine the clinical efficacy of the investigational treatment combination. The primary endpoint will be the Objective Response Rate (ORR), defined by Complete Response (CR) or Partial Response (PR) as measured by RECIST v1.1.

Treatments

Therapies

Immunotherapy; Therapy (NOS)

Medications

Atezolizumab (Tecentriq); CYT107 ()

Inclusion Criteria

Participants must have histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra. Note: mixed histology tumors allowed if predominant histology is urothelial carcinoma Note: small cell or neuroendocrine carcinoma is not allowed if predominant

Participants either may be treatment-naive and considered ineligible for cisplatin-based chemotherapy or have recurrent disease after any prior platinum-based chemotherapy regimen and meet at least one of the following criteria: (a) Glomerular filtration rate ≥ 30 mL/min and > Participants must have measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI)

ECOG performance status ≤ 2 (Karnofsky ≥ 60%)

Participants must have a life expectancy of greater or equal to 12 weeks

Adequate organ and bone marrow function as outlined per protocol.

International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (this applies only to participants who do not receive therapeutic anticoagulation; participants receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)

Participants must provide tissue from an archival tumor sample (obtained within 2 years from screening visit) or newly obtained core, punch, or excisional biopsy of a tumor lesion if deemed relatively safe and technically feasible

Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of study agent(s); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Participants must have the ability to understand and the willingness to sign a written informed consent document

Participants positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive participants must have: (a) A stable regimen of highly active antiretroviral therapy (HAART) (b) No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections (c) A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR) -based tests.

Participants who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma Note: prior perioperative chemotherapy is allowed and is not counted as a line of therapy

Exclusion Criteria

Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation

Participants who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or systemic mitomycin C) before the initiation of study treatment

Participants who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1); however, the following therapies are allowed: (a) Hormone-replacement therapy or oral contraceptives (b) Herbal therapy ≥ 1 week before initiation of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week before initiation of study treatment) (c) Palliative radiotherapy for bone metastases > 2 weeks before initiation of study treatment

Participants who have received prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway -targeting agents

Participants who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: (a) Minimum of 12 weeks from the first dose of anti-CTLA-4 and >6 weeks from the last dose (b) No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)

Participants who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment

Participants who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment

Participants who have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti TNF] agents) within 2 weeks before initiation of study treatment. Participants who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled. The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for participants with orthostatic hypotension or adrenocortical insufficiency is allowed

Participants taking bisphosphonate therapy for symptomatic hypercalcemia. Note: use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed

Participants requiring treatment with a receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor (e.g., denosumab) who cannot discontinue it before initiation of study treatment

Participants with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with some exceptions, per protocol.

Participants with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

Participants who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

Participants with known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver/nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); and inherited liver disease. Participants with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)

Other exclusions apply

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