| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Pancreatic Ductal Adenocarcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10051971 |
| E.1.2 | Term | Pancreatic adenocarcinoma |
| 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 |
Part 1 (Dose Escalation):
To assess the safety and tolerability of oleclumab plus durvalumab in combination with chemotherapy administered in subjects with metastatic PDAC.
Part 2 (Dose Expansion):
To evaluate the preliminary antitumor activity of oleclumab with or without durvalumab in combination with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel administered in subjects with 1L metastatic PDAC.
To evaluate the preliminary antitumor activity of oleclumab with or without durvalumab in combination with mFOLFOX compared to mFOLFOX administered in subjects with 2L metastatic PDAC. |
|
| E.2.2 | Secondary objectives of the trial |
Part 1:To evaluate the preliminary antitumor activity of oleclumab with or without durvalumab in combination with chemotherapy administered in subjects with 1L metastatic PDAC and in subjects with 2L metastatic PDAC.
Part 2: To assess the safety and tolerability of oleclumab with or without durvalumab in combination with chemotherapy administered in subjects with metastatic PDAC.
To evaluate the preliminary antitumor activity of oleclumab with or without durvalumab in combination with chemotherapy compared to chemotherapy alonein subjects with 1L metastatic PDAC and in subjects with 2L metastatic PDAC. To evaluate the preliminary antitumor activity of oleclumab with or without durvalumab in combination with chemotherapy compared to chemotherapy alone in the population defined by CD73
expression.
Part 1 and 2:
To assess the immunogenicity and the PK profile of oleclumab and durvalumab in combination with chemotherapy administered in subjects with metastatic PDAC. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age ≥ 18
2. Written and signed informed consent must be obtained
3. ECOG Performance Status 0 or 1
4. Weight ≥ 35 kg
5. Subjects must have histologically or cytologically confirmed pancreatic adenocarcinoma:
Cohort A: Subjects with previously untreated metastatic pancreatic adenocarcinoma (1 line metastatic disease) not previously treated with systemic therapies.
Cohort B: Subjects with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin) 2 line metastatic adenocarcinoma
6. Subjects must have at least 1 measurable lesion according to RECIST v1.1
7. All subjects must consent to providing archival tumor specimens |
|
| E.4 | Principal exclusion criteria |
1. Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment.
2. Prior receipt of any immune-related therapy
3. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
4. Subjects with a history of venous thrombosis within the past 3 months
5. Subjects with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months prior to start of treatment
6. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
7. Other invasive malignancy within 2 years.
8. Any history of leptomeningeal disease or cord compression.
9. Current or prior use of immunosuppressive medication within 14 days prior to the first dose |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Safety End Points Study Part 1:
• Dose limiting toxicities (DLTs)
• Incidence of adverse events (AEs) and serious adverse events (SAEs)
• Clinically meaningful changes from baseline in clinical laboratory parameters, vital signs, and electrocardiogram (ECG) results
2. Clinical End Points Study Part 2:
• Objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Safety assessment from time of informed consent through 12 weeks after last dose of investigational product
2. Objective response rates during treatment through study completion, about 2 years after the last subject dosed |
|
| E.5.2 | Secondary end point(s) |
1. Safety End Points Study Part 2 :
Incidence of adverse events (AEs), serious adverse events (SAEs). Clinically meaningful changes from baseline in clinical laboratory parameters, vital signs, and ECG results
2. Clinical End Points Study Part 1:
Objective response rate (OR) and disease control (DC) according to RECIST v1.1 in dose escalation
3. Clinical End Points Study Part 2 : Overall Survival (OS); Progression Free Survival (PFS), Duration of Response (DoR), and Disease Control (DC), defined as complete response (CR), partial response (PR) or stable disease (SD) according to RECIST v1.1 in dose expansion
4.Clinical End Points Study Part 2: Overall Survival (OS); Objective Response (OR) and Progression-Free Survival (PFS) according to RECIST v1.1 by CD73 expression at baseline
Part 1 (Dose Escalation) and Part 2 (Dose Expansion):
5. Immunogenicity:
Development of detectable anti-drug antibody(ADA) to oleclumab (MEDI9447) and durvalumab
6. Pharmacokinetic:
Measure of serum Oleclumab (MEDI9447), durvalumab and selected chemotherapies and /or their metabolites |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From time of informed consent through 12 weeks after last dose of investigational product
2. During treatment through study completion, about 2 years after the last subject dosed
3. During treatment through study completion, about 2 years after the last subject dosed
4. From time of screening through study completion, about 2 years after the last subject dosed
5. From start of treatment through 12 weeks post last dose of investigational product
6. During treatment through 12 weeks post last dose of investigational product and through the first 12 weeks of treatment for chemotherapies |
|
| 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 |
| Phase Ib: Safety and pharmacokinetics |
|
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| gemcitabine, nab-paclitaxel, and mFOLFOX |
|
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| 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 |
| United States |
| Norway |
| Spain |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 21 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
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