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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04888312
Other study ID # A-20-1013-C-03
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date September 17, 2021
Est. completion date June 30, 2025

Study information

Verified date April 2024
Source Alligator Bioscience AB
Contact Philip Van Der Veen
Phone +44(0) 1293 510319
Email PVanDerVeen@Theradex.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Phase 1b/2 study to assess the safety and efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.


Description:

OPTIMIZE-1 is a phase 1b/2, open-label, multi-center study assessing the clinical efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma. The efficacy of intravenously administered mitazalimab in combination with the standard of care chemotherapy mFOLFIRINOX will be evaluated in patients with metastatic pancreatic ductal adenocarcinoma. Two dose levels of mitazalimab, 450 ug/kg and 900 ug/kg, are planned to be evaluated together with mFOLFIRINOX for determination of recommended phase 2 dose (RP2D) of mitazalimab in combination with mFOLFIRINOX before entering a dose expansion part with RP2D obtained. The expansion part will evaluate the clinical efficacy of mitazalimab in combination with mFOLFIRINOX assessing objective response rate (ORR), primary endpoint, as well as Progression-free survival (PFS) and Overall survival (OS). The dose expansion part includes a Simon´s two-stage design with an interim analysis for stop for futility or efficacy based on ORR.


Recruitment information / eligibility

Status Recruiting
Enrollment 90
Est. completion date June 30, 2025
Est. primary completion date February 28, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 lesions) 8. Has a life expectancy of = 3 months 9. Has acceptable hematologic laboratory values defined as: 1. Neutrophils = 1.5 x 109/L without growth factor stimulation within 3 weeks prior to the blood test 2. Platelets =100 x 109/L 3. Hemoglobin =6.2 mmol/L (~100 g/L) (may be after transfusion) 10. Has acceptable clinical chemistry laboratory values defined as: 1. Bilirubin =1.5 x ULN (biliary drainage is permitted) 2. AST =3 x ULN (irrespective of hepatic metastases) 3. ALT =3 x ULN (irrespective of hepatic metastases) 4. Creatinine =1.5 x ULN or glomerular filtration rate (GFR) of =45 mL/min 5. INR =1.5 x ULN 6. Albumin =28 g/L 11. For women of childbearing potential1: 1. Has a negative highly sensitive serum (ß-human chorionic gonadotropin [ß-hCG]) pregnancy test at screening 2. Is willing to use highly effective contraception methods during study treatment and for at least six months thereafter 12. Fertile men must practice effective contraceptive methods (i.e. surgical sterilization, or a condom used with a spermicide) during study treatment and for at least six months thereafter 13. Is willing to comply with all study procedures 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 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 13. Participates in another investigational drug or device study with any intervention within the previous 4 weeks prior to first dose of mitazalimab 14. Has received prior treatment with irinotecan or platinum-containing chemotherapy 15. Has pre-existing peripheral neuropathy greater than grade 1 16. Has known Gilbert's disease 17. Has known genotype UGT1A1 * 28 / * 28 18. Has known fructose intolerance (malabsorption) 19. Has complete dihydropyrimidine dehydrogenase (DPD) deficiency

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
CD40 agonist mitazalimab in combination with chemotherapy
Mitazalimab administered intravenously every 14 days in combination with standard of care chemotherapy modified FOLFIRINOX.

Locations

Country Name City State
Belgium Cliniques Universitaires St-Luc Brussels
Belgium Hospital Erasme Bruxelles
Belgium Grand Hôpital de Charleroi Charleroi
Belgium UZA Antwerp Edegem
Belgium Universitair Ziekenhuis Gent Gent
France Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque, Bordeaux
France Centre Lyon Berard Lyon
France Institut Paoli-Calmettes Marseille
France Hopital Européen Georges Pompidou Paris
France Institute de Cancérologie de l'Ouest Saint-Herblain
France Institute de Cancérologie de Lorraine Vandœuvre-lès-Nancy
Spain Hospital Universitario Vall d'Hebron, Barcelona, Spain Barcelona
Spain Hospital Universitario La Paz, Madrid, Spain Madrid
Spain Hospital Universitario Ramon y Cajal, Madrid, Spain Madrid
Spain Hospital Universitario Virgen del Rocio, Sevilla, Spain Sevilla
Spain Hospital Universitario Miguel Servet, Zaragoza, Spain Zaragoza

Sponsors (3)

Lead Sponsor Collaborator
Alligator Bioscience AB 4Pharma Ltd., Theradex

Countries where clinical trial is conducted

Belgium,  France,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Dose Limiting Toxicities (DLTs) (Part 1: Phase 1b Dose escalation) Number of patients experiencing DLTs From first dose to end of dose limiting toxicity period (Day 1-21)
Primary Objective response rate (ORR) (Part 2: Phase 2 Dose expansion) Proportion of patients achieving complete response or partial response at any time during the study From first dose to 28-56 days after end of study treatment
Secondary Type, frequency and severity of Adverse Events Number of patients experiencing AEs. Number of events summarized by SOC and preferred term. From informed consent signed to 28-56 days after end of of study treatment
Secondary Anti-drug-antibody (ADA) titer in serum (tolerability) Immunogenicity of mitazalimab From first dose until 28-56 days after end of study treatment
Secondary Cmax of mitazalimab (pharmacokinetics) Cmax derived from mitazalimab serum concentrations From first dose until 28-56 days after end of study treatment
Secondary Tmax of mitazalimab (pharmacokinetics) Tmax derived from mitazalimab serum concentrations From first dose until 28-56 days after end of study treatment
Secondary AUC(0-T) of mitazalimab (pharmacokinetics) AUC(0-T) derived from mitazalimab serum concentrations From first dose until 28-56 days after end of study treatment
Secondary Anti-tumor Activity per RECIST 1.1 guideline (efficacy) Best overall response, duration of response, Duration of stable disease, disease control rate, Time to next anti-cancer therapy will be assessed From first dose until 28-56 days after end of study treatment
Secondary Progression free survival (efficacy) Number of days from first dose of mitazalimab to progressive disease or death. From first dose and up to 2 years after end of study treatment
Secondary Overall survival (efficacy) Number of days from first dose of mitazalimab until death From first dose and up to 2 years after end of study treatment
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