E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Urothelial Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Advanced or metastatic urothelial carcinoma is a type of cancer that develops in the lining of the urinary tract mainly affecting the urinary bladder and other parts of the urinary tract. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab in patients enrolled irrespective of tumor programmed death-Ligand 1 (PD-L1) score, as measured by progression-free survival (PFS) and overall survival (OS). |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab in patients enrolled irrespective of tumor PD-L1 score, as measured by objective response (OR) and duration of response (DOR).
•To evaluate the efficacy of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab in a subgroup of patients defined by tumor PD-L1 score.
•To evaluate the safety of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab
•To characterize pharmacokinetics of MOXR0916 and atezolizumab when administered in combination
•To evaluate the immune response to MOXR0916 and atezolizumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
- Life expectancy >= 12 weeks
- Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC)
- Availability of a representative tumor specimen to enable central testing for determination of PD-L1 status and exploratory research on biomarkers
- No prior systemic therapy for inoperable locally advanced or metastatic UC
- Ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria:
Impaired renal function (glomerular filtration rate [GFR] > 30 but < 60 mililitre/minute); National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0 Grade >= 2 audiometric hearing loss (25 Decibel at two contiguous frequencies or more severe);
NCI CTCAE v 4.0 Grade >= 2 peripheral neuropathy;
ECOG Performance Status of 2
- Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study treatment
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm |
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E.4 | Principal exclusion criteria |
- Pregnant or lactating, or intending to become pregnant or breast feed during the study or 6 months afterward
- Significant cardiovascular disease, such as New York Heart Association cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease
- Major surgical procedure within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug
- Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment except palliative radiotherapy for bone metastases or soft tissue lesions that is completed > 7 days prior to baseline imaging; radiotherapy for brain metastases; prior local intravesical chemotherapy or immunotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment; hormone-replacement therapy or oral contraceptives; patients should be recovered from any toxicities associated with permitted anti-cancer therapies
- Prior treatment with CD137 or OX40 agonists, anti− cytotoxic T-lymphocyte-associated protein (CTLA4), anti−PD-1, anti−PD-L1, anti-CD-27, anti- Glucocorticoid-induced tumor necrosis factor receptor (GITR) therapeutic antibody or pathway-targeting agents
- Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to initiation of study treatment
- Untreated central nervous system (CNS) metastases or active (progressing or requiring corticosteroids for symptomatic control) CNS metastases
- Any history of leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled tumor-related pain
- Malignancies other than UC within 5 years prior to Cycle 1, Day 1
- Uncontrolled or symptomatic hypercalcemia
- History of autoimmune disease
- Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
- Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is longer, prior to initiation of study treatment
- History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan
- Active hepatitis B and C virus infection
- Positive HIV test at screening
- Active tuberculosis
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Prior allogeneic stem cell or solid organ transplantation
- Treatment with a live, attenuated vaccine within 4 weeks before initiation of study treatment, or anticipation of need for such a vaccine during the course of the study
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells
- Known allergy or hypersensitivity to any component of the atezolizumab formulation and the MOXR0916 formulation
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E.5 End points |
E.5.1 | Primary end point(s) |
1.PFS (in patients enrolled irrespective of tumor PD-L1 score) as determined by the investigator according to RECIST v1.1
2.OS (in patients enrolled irrespective of tumor PD-L1 score)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to approximately 45 months |
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E.5.2 | Secondary end point(s) |
1.PFS according to RECIST v1.1 and OS, in patients defined by tumor PD-L1 score
2.OR and DOR according to RECIST v1.1
3.Incidence of adverse events
4.Serum concentrations and presence of anti-therapeutic antibodies to MOXR0916 and atezolizumab
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Up to approximately 45 months
4. At specified time points up to 120 days after last dose of study treatment
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and Biomarkers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Canada |
Denmark |
France |
Germany |
Netherlands |
Portugal |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date when the number of OS events specified for the final analysis in Section 6.4 has been observed. Additionally, the Sponsor may decide to terminate the study at any time. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |