E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
clear-cell renal cell carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038407 |
E.1.2 | Term | Renal cell cancer |
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 |
Dose-escalation: To determine the maximum tolerated dose (MTD) or the highest protocol-defined dose in the absence of exceeding the MTD for MEDI0680 in combination with durvalumab and the safety profile of MEDI0680 in combination with durvalumab in subjects with advanced malignancies Dose-expansion: To evaluate the objective response rate of MEDI0680 in combination with durvalumab versus nivolumab monotherapy in immunotherapy-naïve subjects with advanced or metastatic ccRCC as based on investigator assessed response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
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E.2.2 | Secondary objectives of the trial |
Dose-escalation: Evaluate the objective response rate of MEDI0680 in combination with durvalumab in subjects with advanced malignancies as based on the investigator assessed response using modified RECIST v1.1 Dose-expansion: Describe the safety and tolerability of MEDI0680 in combination with durvalumab or nivolumab monotherapy in immunotherapy-naïve subjects with advanced or metastatic ccRCC Evaluate the objective response rate of MEDI0680 in combination with durvalumab versus nivolumab monotherapy in immunotherapy-naïve subjects with advanced or metastatic ccRCC as based on blinded independent central review (BICR) assessed response using RECIST v1.1 Dose-escalation and Dose-expansion: 1. Describe the pharmacokinetics (PK) of MEDI0680 in combination with durvalumab 2. Determine the immunogenicity of MEDI0680 in combination with durvalumab 3. Determine whether PD-L1 is a predictive biomarker for response to therapy with MEDI0680 in combination with durvalumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Must be 18 years or older -Eastern Cooperative Oncology Group performance status of 0-1 -Adequate organ function -No more than 1 prior line of therapy
For complete list of inclusion criteria please refer to the protocol |
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E.4 | Principal exclusion criteria |
-Concurrent enrollment in another clinical study, unless in follow-up period or it is an observational study -Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment -Prior treatment with immunotherapy
For complete list of exclusion criteria please refer to the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose Escalation: Safety assessment will include adverse events and serious adverse events as well as changes from baseline in lab parameters, vital signs, physical examination, and ECG results
Dose Expansion: Antitumor activity assessment will be based on an application of RECIST v1.1 to investigator-assessed tumor measurements |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Dose Escalation: From First dose of study drugs to 90 days after the last dose of study drug administration
Dose Expansion: From the first dose of study drugs through study completion. |
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E.5.2 | Secondary end point(s) |
Dose Escalation: 1. Antitumor activity of MEDI0680 in combination with MEDI4736 in subjects with advanced malignancies using modified RECIST v1.1
Dose Expansion: 2. Safety of MEDI0680 in combination with MEDI4736
3. Antitumor activity of MEDI0680 in combination with MEDI4736
4. Both Phases: Pharmacokinetics of MEDI0680 in combination with MEDI4736
5. Both Phases: Immunogenicity of MEDI0680 and MEDI4736
6. PD-L1 as a predictive biomarker |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From the first dose of study drugs through study completion
2. From First dose of study drugs to 90 days after the last dose of study drug administration
3. From the first dose of study drugs through study completion
4. From the first dose of study drugs through 12 months after the last dose of study drugs
5. From the first dose of study drugs through 12 months after the last dose of study drugs
6. From the first dose of study drugs through study completion |
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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 | 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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1/2 Dose Expansion Study |
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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 | Yes |
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 | No |
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 | 8 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Australia |
Canada |
France |
Korea, Republic of |
Netherlands |
United Kingdom |
United States |
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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
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Per protocol, the end of study is defined as 2 years after the last subject enrolls or the date the study is closed by the sponsor, whichever occurs first |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |