Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients (OPTIMIZE-1)
Primary Purpose
Metastatic Pancreatic Ductal Adenocarcinoma
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CD40 agonist mitazalimab in combination with chemotherapy
Sponsored by

About this trial
This is an interventional treatment trial for Metastatic Pancreatic Ductal Adenocarcinoma focused on measuring mitazalimab, modified FOLFIRINOX, Pancreatic ductal adenocarcinoma, PDAC, Pancreatic Cancer, Chemotherapy, combination, 5-Fluorouracil, Oxaliplatin, Leucovorin, Irinotecan
Eligibility Criteria
Inclusion Criteria:
- Has provided written informed consent
- Is ≥18 years of age at the time of signing the informed consent form (ICF)
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Has a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma (histologically documented)
- Has measurable disease per RECIST v. 1.1
- Has not received previous chemotherapy for pancreatic ductal adenocarcinoma
- Has not received prior abdominal radiotherapy (except for palliative radiotherapy to non-target lesions)
- Has a life expectancy of ≥ 3 months
Has acceptable hematologic laboratory values defined as:
- Neutrophils ≥ 1.5 x 109/L without growth factor stimulation within 3 weeks prior to the blood test
- Platelets ≥100 x 109/L
- Hemoglobin ≥6.2 mmol/L (~100 g/L) (may be after transfusion)
Has acceptable clinical chemistry laboratory values defined as:
- Bilirubin ≤1.5 x ULN (biliary drainage is permitted)
- AST ≤3 x ULN (irrespective of hepatic metastases)
- ALT ≤3 x ULN (irrespective of hepatic metastases)
- Creatinine ≤1.5 x ULN or glomerular filtration rate (GFR) of ≥45 mL/min
- INR ≤1.5 x ULN
- Albumin ≥28 g/L
For women of childbearing potential1:
- Has a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test at screening
- Is willing to use highly effective contraception methods during study treatment and for at least six months thereafter
- 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
- Is willing to comply with all study procedures
Exclusion Criteria:
- Has other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cyst adenocarcinoma and ampullary carcinoma
- 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
- Has known CNS metastases or carcinomatous meningitis
- Has contraindication to any constituent of study treatment (mitazalimab and applicable chemotherapy)
- Has a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
- 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
- Has QTc >450 msec
- Has uncontrolled intercurrent illness, including active infection
- Has a known history of HIV, hepatitis B or active hepatitis C infection
- Is a female patient who is pregnant or nursing
- Has received attenuated vaccine within 28 days before the first dose of study treatment
- 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
- Participates in another investigational drug or device study with any intervention within the previous 4 weeks prior to first dose of mitazalimab
- Has received prior treatment with irinotecan or platinum-containing chemotherapy
- Has pre-existing peripheral neuropathy greater than grade 1
- Has known Gilbert's disease
- Has known genotype UGT1A1 * 28 / * 28
- Has known fructose intolerance (malabsorption)
- Has complete dihydropyrimidine dehydrogenase (DPD) deficiency
Sites / Locations
- Cliniques Universitaires St-Luc
- Hospital Erasme
- Grand Hôpital de Charleroi
- UZA Antwerp
- Universitair Ziekenhuis Gent
- Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque,
- Centre Lyon Berard
- Institut Paoli-Calmettes
- Hopital Européen Georges Pompidou
- Institute de Cancérologie de Lorraine
- Hospital Universitario Vall d'Hebron, Barcelona, Spain
- Hospital Universitario La Paz, Madrid, Spain
- Hospital Universitario Ramon y Cajal, Madrid, Spain
- Hospital Universitario Virgen del Rocio, Sevilla, Spain
- Hospital Universitario Miguel Servet, Zaragoza, Spain
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intravenously administered mitazalimab given in combination with chemotherapy
Arm Description
Mitazalimab, a human monoclonal antibody targeting CD40, administered intravenously every 14 days, in combination with standard of care chemotherapy modified FOLFIRINOX.
Outcomes
Primary Outcome Measures
Incidence of Dose Limiting Toxicities (DLTs) (Part 1: Phase 1b Dose escalation)
Number of patients experiencing DLTs
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
Secondary Outcome Measures
Type, frequency and severity of Adverse Events
Number of patients experiencing AEs. Number of events summarized by SOC and preferred term.
Anti-drug-antibody (ADA) titer in serum (tolerability)
Immunogenicity of mitazalimab
Cmax of mitazalimab (pharmacokinetics)
Cmax derived from mitazalimab serum concentrations
Tmax of mitazalimab (pharmacokinetics)
Tmax derived from mitazalimab serum concentrations
AUC(0-T) of mitazalimab (pharmacokinetics)
AUC(0-T) derived from mitazalimab serum concentrations
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
Progression free survival (efficacy)
Number of days from first dose of mitazalimab to progressive disease or death.
Overall survival (efficacy)
Number of days from first dose of mitazalimab until death
Full Information
NCT ID
NCT04888312
First Posted
May 6, 2021
Last Updated
October 5, 2023
Sponsor
Alligator Bioscience AB
Collaborators
Theradex, 4Pharma Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04888312
Brief Title
Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients
Acronym
OPTIMIZE-1
Official Title
An Open-label Phase 1b/2 Study Assessing the Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 17, 2021 (Actual)
Primary Completion Date
February 28, 2024 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alligator Bioscience AB
Collaborators
Theradex, 4Pharma Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
Phase 1b/2 study to assess the safety and efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Ductal Adenocarcinoma
Keywords
mitazalimab, modified FOLFIRINOX, Pancreatic ductal adenocarcinoma, PDAC, Pancreatic Cancer, Chemotherapy, combination, 5-Fluorouracil, Oxaliplatin, Leucovorin, Irinotecan
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenously administered mitazalimab given in combination with chemotherapy
Arm Type
Experimental
Arm Description
Mitazalimab, a human monoclonal antibody targeting CD40, administered intravenously every 14 days, in combination with standard of care chemotherapy modified FOLFIRINOX.
Intervention Type
Biological
Intervention Name(s)
CD40 agonist mitazalimab in combination with chemotherapy
Other Intervention Name(s)
ADC-1013, JNJ-64457107
Intervention Description
Mitazalimab administered intravenously every 14 days in combination with standard of care chemotherapy modified FOLFIRINOX.
Primary Outcome Measure Information:
Title
Incidence of Dose Limiting Toxicities (DLTs) (Part 1: Phase 1b Dose escalation)
Description
Number of patients experiencing DLTs
Time Frame
From first dose to end of dose limiting toxicity period (Day 1-21)
Title
Objective response rate (ORR) (Part 2: Phase 2 Dose expansion)
Description
Proportion of patients achieving complete response or partial response at any time during the study
Time Frame
From first dose to 28-56 days after end of study treatment
Secondary Outcome Measure Information:
Title
Type, frequency and severity of Adverse Events
Description
Number of patients experiencing AEs. Number of events summarized by SOC and preferred term.
Time Frame
From informed consent signed to 28-56 days after end of of study treatment
Title
Anti-drug-antibody (ADA) titer in serum (tolerability)
Description
Immunogenicity of mitazalimab
Time Frame
From first dose until 28-56 days after end of study treatment
Title
Cmax of mitazalimab (pharmacokinetics)
Description
Cmax derived from mitazalimab serum concentrations
Time Frame
From first dose until 28-56 days after end of study treatment
Title
Tmax of mitazalimab (pharmacokinetics)
Description
Tmax derived from mitazalimab serum concentrations
Time Frame
From first dose until 28-56 days after end of study treatment
Title
AUC(0-T) of mitazalimab (pharmacokinetics)
Description
AUC(0-T) derived from mitazalimab serum concentrations
Time Frame
From first dose until 28-56 days after end of study treatment
Title
Anti-tumor Activity per RECIST 1.1 guideline (efficacy)
Description
Best overall response, duration of response, Duration of stable disease, disease control rate, Time to next anti-cancer therapy will be assessed
Time Frame
From first dose until 28-56 days after end of study treatment
Title
Progression free survival (efficacy)
Description
Number of days from first dose of mitazalimab to progressive disease or death.
Time Frame
From first dose and up to 2 years after end of study treatment
Title
Overall survival (efficacy)
Description
Number of days from first dose of mitazalimab until death
Time Frame
From first dose and up to 2 years after end of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has provided written informed consent
Is ≥18 years of age at the time of signing the informed consent form (ICF)
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Has a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma (histologically documented)
Has measurable disease per RECIST v. 1.1
Has not received previous chemotherapy for pancreatic ductal adenocarcinoma
Has not received prior abdominal radiotherapy (except for palliative radiotherapy to non-target lesions)
Has a life expectancy of ≥ 3 months
Has acceptable hematologic laboratory values defined as:
Neutrophils ≥ 1.5 x 109/L without growth factor stimulation within 3 weeks prior to the blood test
Platelets ≥100 x 109/L
Hemoglobin ≥6.2 mmol/L (~100 g/L) (may be after transfusion)
Has acceptable clinical chemistry laboratory values defined as:
Bilirubin ≤1.5 x ULN (biliary drainage is permitted)
AST ≤3 x ULN (irrespective of hepatic metastases)
ALT ≤3 x ULN (irrespective of hepatic metastases)
Creatinine ≤1.5 x ULN or glomerular filtration rate (GFR) of ≥45 mL/min
INR ≤1.5 x ULN
Albumin ≥28 g/L
For women of childbearing potential1:
Has a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test at screening
Is willing to use highly effective contraception methods during study treatment and for at least six months thereafter
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
Is willing to comply with all study procedures
Exclusion Criteria:
Has other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cyst adenocarcinoma and ampullary carcinoma
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
Has known CNS metastases or carcinomatous meningitis
Has contraindication to any constituent of study treatment (mitazalimab and applicable chemotherapy)
Has a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
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
Has QTc >450 msec
Has uncontrolled intercurrent illness, including active infection
Has a known history of HIV, hepatitis B or active hepatitis C infection
Is a female patient who is pregnant or nursing
Has received attenuated vaccine within 28 days before the first dose of study treatment
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
Participates in another investigational drug or device study with any intervention within the previous 4 weeks prior to first dose of mitazalimab
Has received prior treatment with irinotecan or platinum-containing chemotherapy
Has pre-existing peripheral neuropathy greater than grade 1
Has known Gilbert's disease
Has known genotype UGT1A1 * 28 / * 28
Has known fructose intolerance (malabsorption)
Has complete dihydropyrimidine dehydrogenase (DPD) deficiency
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sumeet Ambarkhane, MD
Organizational Affiliation
Alligator Bioscience AB
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jean-Luc van Laethem, Prof. MD
Organizational Affiliation
Hospital Erasme
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cliniques Universitaires St-Luc
City
Brussels
Country
Belgium
Facility Name
Hospital Erasme
City
Bruxelles
Country
Belgium
Facility Name
Grand Hôpital de Charleroi
City
Charleroi
Country
Belgium
Facility Name
UZA Antwerp
City
Edegem
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque,
City
Bordeaux
Country
France
Facility Name
Centre Lyon Berard
City
Lyon
Country
France
Facility Name
Institut Paoli-Calmettes
City
Marseille
Country
France
Facility Name
Hopital Européen Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Institute de Cancérologie de Lorraine
City
Vandœuvre-lès-Nancy
Country
France
Facility Name
Hospital Universitario Vall d'Hebron, Barcelona, Spain
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario La Paz, Madrid, Spain
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal, Madrid, Spain
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio, Sevilla, Spain
City
Sevilla
Country
Spain
Facility Name
Hospital Universitario Miguel Servet, Zaragoza, Spain
City
Zaragoza
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients
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