E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1:
To assess safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or the highest protocol-defined dose level in the absence of establishing an MTD of durvalumab in combination with monalizumab in subjects with selected advanced solid tumors.
Part 2:
To assess further the safety and tolerability of either the MTD or the highest protocol-defined dose level, in the absence of establishing an MTD, of durvalumab in combination with monalizumab in subjects with selected advanced solid tumors.
Part 3:
To assess safety and tolerability of durvalumab in combination with monalizumab plus chemotherapy with or without a biologic agent, as clinically indicated in subjects with MSS-CRC.
Please refer to the protocol for a full list of the Primary objectives. |
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E.2.2 | Secondary objectives of the trial |
For the combinations under investigation in this trial:
• To evaluate preliminary anti-tumor activity
• To further evaluate the anti-tumor activity
• To describe the pharmacokinetics (PK) of each agent in the combinations under investigation
• To describe the immunogenicity
• To characterise the association between clinical and/or pre-treatment expression of PD-L1 and human leukocyte antigen (HLA-E) within the tumor microenvironment
Please refer to the protocol for a full list of the secondary objectives. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must have histologic documentation of advanced recurrent or metastatic cancer.
2. Subjects must be at the recurrent/metastatic setting, with selected advanced solid tumors.
3. Subjects must have at least one lesion that is measurable by RECIST v1.1
4. Part 3, Dose exploration, CRC subjects can be treatment naïve but should not have received more than two lines of systemic therapy in the recurrent/metastatic setting.
Please refer to the protocol for a full list of the inclusion criteria. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor.
2. Prior participation in clinical studies that include durvalumab alone or in combination, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed
3. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment
4. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable
Please refer to the protocol for a full list of the exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety as assessed by presence of adverse
events (AEs), serious adverse events (SAEs), DLTs, abnormal laboratory
parameters, vital signs, and electrocardiogram (ECG) results. AEs will be
graded according to the National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI CTCAE) v4.03.
The primary endpoint for evaluating clinical activity in Part 3 (Cohorts
C1A and C1B) is objective response (OR) by investigator assessment per
RECIST v1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout the study |
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E.5.2 | Secondary end point(s) |
1 The endpoints for assessment of antitumor activity will include
objective response (OR [primary endpoint for Cohorts C1A and C1B]),
disease control (DC), duration of response (DoR), and progression-free
survival (PFS) by investigator assessment per RECIST v1.1. Overall
survival (OS) will also be assessed.
2 The endpoints for assessment of PK include individual subjects'
investigational product concentrations in serum at
different time points after administration of these agents.
3 The endpoints for assessment of immunogenicity include the number
and percentage of subjects who develop detectable anti-drug antibodies
(ADAs).
4 The endpoints for assessment of biomarkers predicting subject clinical
outcomes will include expression of PD-L1 and HLA-E in pre-treatment
tumor biopsies. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout the study |
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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 | Yes |
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 |
First Administration to cancer subjects |
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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 | 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 | 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.8.3 |
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 | 15 |
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 |
Belgium |
Brazil |
Canada |
France |
Hungary |
Italy |
Korea, Republic of |
New Zealand |
Spain |
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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5 years after the final subject is enrolled 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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |