E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients (age ≥18 years) with advanced and metastatic solid tumors including but not limited to histologically or cytologically documented UBC, PDAC, or TNBC. |
|
E.1.1.1 | Medical condition in easily understood language |
Urothelial bladder cancer /Triple-negative breast cancer /Pancreatic ductal adenocarcinoma |
|
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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033599 |
E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071664 |
E.1.2 | Term | Bladder transitional cell carcinoma metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10075566 |
E.1.2 | Term | Triple negative breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
Objective response rate (ORR) of tremelimumab monotherapy |
|
E.2.2 | Secondary objectives of the trial |
1. To further assess the efficacy of tremelimumab monotherapy.
2. To assess the efficacy of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥18 years at the time of screening
2. Written informed consent and any locally required authorization
3. Patients affected by histologically or cytologically documented solid tumor malignancies, including but not limited to 1 of the following:
-UBC
-Metastatic PDAC
-TNBC.
- Are intolerant, are ineligible for, or have refused treatment with standard first-line therapy for UBC, Metastatic PDAC or TNBC
4. Willing to give valid written consent to provide a tumor biopsy,
archival or fresh
(preferred), for the purpose of establishing PD-L1 status and for exploratory
biomarker analyses
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. At least 1 lesion, not previously irradiated, that can be accurately measured at
baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have
short axis ≥15 mm) with computed tomography (CT) (preferred) or magnetic
resonance imaging (MRI) scans, preferably with IV contrast, and that is suitable for
accurate repeated measurements as per RECIST 1.1 guidelines. Lesions in a previously irradiated field can be used as measurable disease provided that there has
been demonstrated progression in the lesion.
7.No prior exposure to immune-mediated therapy, including but not limited to other
anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines.
8. Adequate organ and marrow function
9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for
female pre-menopausal patients.
|
|
E.4 | Principal exclusion criteria |
1. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
2. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives
3. Receipt of last dose of an approved (marketed) anticancer therapy within 21 days prior to the first dose of study treatment.
4. Current or prior use of immunosuppressive medication within 14 days before the first dose of therapy.
5. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment.
6. History of active primary immunodeficiency
7. Known allergy or hypersensitivity to IP or any IP excipient |
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E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Duration of response
2. Disease control rate
3. Progression-free survival
4. Overall survival
5. Best objective response |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Belgium |
Korea, Republic of |
Netherlands |
Poland |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The data cut-off for the primary analysis of all study endpoints including OS, will take place approximately 12 months after the last patient completes 12 months of initial Treme Monotherapy, or the last patient has withdrawn from the study, or the study is discontinued by the sponsor. A final data cut-off of OS and safety will be conducted approximately 6 months after the primary analysis data cut-off. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |