| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Pancreatic Ductal Adenocarcinoma |
| adénocarcinome canalaire pancréatique en phase métastatique |
|
| E.1.1.1 | Medical condition in easily understood language |
| Pancreatic Cancer |
| Cancer du pancréas |
|
| 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 | PT |
| E.1.2 | Classification code | 10073364 |
| E.1.2 | Term | Ductal adenocarcinoma of pancreas |
| 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 (Phase 1b): To determine the recommended Phase 2 dose (RP2D) of mitazalimab in combination with chemotherapy
Part 2 (Phase 2): To assess the clinical activity of mitazalimab in combination with chemotherapy (i.e., anti-tumor activity as per RECIST v. 1.1 guideline) |
PARTIE 1: la dose recommandée pour la Phase II (DRPII) de mitazalimab en association avec la chimiothérapie
PARTIE 2: Évaluer l'activité clinique du mitazalimab en association avec la chimiothérapie (c.-à-d. son activité antitumorale selon la directive RECIST v.1.1) |
|
| E.2.2 | Secondary objectives of the trial |
Part 1 (Phase 1b): To assess the safety and tolerability of mitazalimab in combination with chemotherapy.
To assess the immunogenicity of mitazalimab.
To assess pharmacokinetics (PK) of mitazalimab after single and repeated administrations.
To assess the clinical activity of mitazalimab in combination with chemotherapy (i.e., anti-tumor activity as per RECIST v. 1.1 guideline).
To assess survival outcomes following repeated administrations of mitazalimab in combination with chemotherapy.
Part 2 (Phase 2): To assess the clinical activity of mitazalimab in combination with chemotherapy (i.e., anti-tumor activity as per RECIST v. 1.1 guideline).
To assess survival outcomes following repeated administrations of mitazalimab in combination with chemotherapy.
To assess the safety and tolerability of mitazalimab in combination with chemotherapy.
To assess the immunogenicity of mitazalimab.
To assess pharmacokinetics (PK) of mitazalimab after single and repeated administrations.
|
PARTIE 1:Évaluer la sécurité et la tolérance du mitazalimab en association avec la chimiothérapie.
Évaluer l'immunogénicité du mitazalimab
Étudier la pharmacocinétique (PK) du mitazalimab après des administrations uniques et répétées
Évaluer l'activité clinique du mitazalimab en association avec la chimiothérapie (c.-à-d. son activité antitumorale selon la directive RECIST v.1.1)
Évaluer les résultats de survie à la suite d’administrations répétées de mitazalimab en association avec la chimiothérapie
PARTIE 2:Évaluer l'activité clinique du mitazalimab en association avec la chimiothérapie (c.-à-d. son activité antitumorale selon la directive RECIST v.1.1)
Évaluer les résultats de survie à la suite d’administrations répétées de mitazalimab en association avec la chimiothérapie Évaluer la sécurité et la tolérance du mitazalimab en association avec la chimiothérapie Évaluer l'immunogénicité du mitazalimab Évaluer la PK du mitazalimab à la suite d’administrations uniques et répétées |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Has provided written informed consent
2.Is ≥18 years of age at the time of signing the informed consent form (ICF)
3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Has a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma (histologically documented)
5. Has measurable disease per RECIST v. 1.1
6. Has not received previous chemotherapy for pancreatic ductal adenocarcinoma
7. Has not received prior abdominal radiotherapy (except for palliative radiotherapy to non-target l lesions)
8. Has a life expectancy of ≥ 3 months
9. Has acceptable hematologic laboratory values
defined as:
a. Neutrophils ≥ 1.5 x 10^9/L without growth factor
stimulation within 3 weeks prior to the blood test
b. Platelets ≥100 x 10^9/L
c. Hemoglobin ≥5.9 mmol/L (~95 g/L) (may be after transfusion)
10. Has acceptable clinical chemistry laboratory values
defined as:
a. Bilirubin ≤1.5 x ULN (biliary drainage is permitted)
b. AST ≤3 x ULN (irrespective of hepatic metastases)
c. ALT ≤3 x ULN (irrespective of hepatic metastases)
d. Creatinine ≤1.5 x ULN or glomerular filtration rate
(GFR) of ≥45 mL/min (see APPENDIX 4 for calculation of GFR)
e. INR ≤1.5 x ULN
f. Albumin ≥28 g/L
11. For women of childbearing potential:
a. Has a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test at
screening
b. Is willing to use highly effective contraception
methods (defined in APPENDIX 5) during study treatment and for at least six months thereafter
12. Is willing to comply with all study procedures
|
|
| E.4 | Principal exclusion criteria |
1. Has other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar
cell adenocarcinoma, cyst adenocarcinoma and ampullary carcinoma
2. Has other current cancer or history of cancer in
the prior 3 years before signing the ICF other than in situ cervical cancer, or basal cell or squamous cell carcinoma treated with local excision only
3. Has known CNS metastases or carcinomatous meningitis
4. Has contraindication to any constituent of study treatment (mitazalimab and applicable chemotherapy)
5. Has a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
6. Has a history of myocardial infarction within 12 months of the first administration of mitazalimab, uncontrolled angina pectoris, unstable cardiac arrhythmias, or congestive heart failure of New York Heart Association class II or greater
7. Has QTc >450 msec if male and QTc >470 msec if female
8. Has uncontrolled intercurrent illness, including active infection
9. Has a known history of HIV, hepatitis B or active hepatitis C infection
10. Is a female patient who is pregnant or nursing
11. Has received attenuated vaccine within 28 days
before the first dose of study treatment
12. Any condition that, in the opinion of the Investigator, would place the patient at increased risk or preclude the patient’s compliance with the study
Additional exclusion criteria only applicable for mFOLFIRINOX treatment:
13. Has received prior treatment with irinotecan or platinum-containing chemotherapy
14. Has pre-existing peripheral neuropathy greater
than grade 1
15. Has known Gilbert's disease
16. Has known genotype UGT1A1 * 28 / * 28
17. Has known fructose intolerance (malabsorption)
18. Has complete dihydropyrimidine dehydrogenase (DPD) deficiency
Additional exclusion criteria only applicable for gemcitabine plus nab-paclitaxel treatment:
13. Has a history of slowly progressive dyspnea and unproductive cough, or of conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity, pneumonitis or multiple allergies
14. Has a history of Peripheral Artery Disease (eg, claudication, Leo Buerger's disease)
15. Has a history of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa)
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1 (Phase 1b): Incidence of DLTs
Part 2 (Phase 2): Objective response rate (ORR) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1 (Phase 1b):
Mitazalimab in combination with mFOLFIRINOX: The time from the first dose of mitazalimab (Day 1) until Day 21 in the first treatment cycle (Cycle 1).
Mitazalimab in combination with gemcitabine plus nab-paclitaxel: The time from the first dose of mitazalimab (Day 1) until Day 28 within the first treatment
cycle of 35 days (Cycle 1).
Part 2 (Phase 2): Duration of part 2 of the study |
|
| E.5.2 | Secondary end point(s) |
Part 1 (Phase 1b):
•Type, frequency and severity of adverse events (AEs)
•Detection and characterization of anti-drug antibody (ADA) titers in serum
•PK parameters will include Cmax, Tmax, and AUC(0-T). Additional parameters may be calculated depending on data obtained
•Objective response rate (ORR)
•Best Overall Response (BOR), with response categories CR, PR, SD, and PD
•Duration of response (DoR)
•Duration of SD
•Disease control rate
•Time to next anti-cancer therapy
•Progression-free survival (PFS)
•Overall survival (OS)
Part 2 (Phase 2):
•Best Overall Response (BOR), with response categories CR, PR, SD, and PD
•Duration of response (DoR)
•Duration of SD
•Disease control rate
•Time to next anti-cancer therapy
•Progression-free survival (PFS)
•Overall survival (OS)
•Type, frequency and severity of AEs
•Detection and characterization of anti-drug antibody (ADA) titers in serum
•PK parameters will include Cmax, Tmax, and AUC(0-T). Additional parameters may be calculated depending on data obtained
|
|
| 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 | No |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| 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 |
|
| 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 in combination with Chemotherapy |
|
| 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 | 7 |
| 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 | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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 End of Trial is defined as the last study assessment for the last patient on study. |
|
| 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 | 9 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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