Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients (OPTIMIZE-1)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Biological: CD40 agonist mitazalimab in combination with chemotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Philip Van Der Veen; Phone Number: +44(0) 1293 510319; Email: PVanDerVeen@Theradex.com
• Study Contact Backup: Name: Karin Nordbladh; Email: knh@alligatorbioscience.com

Study Locations

• Belgium
  • Brussels, Belgium
    • Cliniques Universitaires St-Luc
  • Bruxelles, Belgium
    • Hospital Erasme
  • Charleroi, Belgium
    • Grand Hôpital de Charleroi
  • Edegem, Belgium
    • UZA Antwerp
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• France
  • Bordeaux, France
    • Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque,
  • Lyon, France
    • Centre Lyon Berard
  • Marseille, France
    • Institut Paoli-Calmettes
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Vandœuvre-lès-Nancy, France
    • Institute de Cancerologie de Lorraine
• Spain
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron, Barcelona, Spain
  • Madrid, Spain
    • Hospital Universitario La Paz, Madrid, Spain
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal, Madrid, Spain
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio, Sevilla, Spain
  • Zaragoza, Spain
    • Hospital Universitario Miguel Servet, Zaragoza, Spain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 (β-human chorionic gonadotropin [β-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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenously administered mitazalimab given in combination with chemotherapy; Mitazalimab, a human monoclonal antibody targeting CD40, administered intravenously every 14 days, in combination with standard of care chemotherapy modified FOLFIRINOX.	Biological: CD40 agonist mitazalimab in combination with chemotherapy; Mitazalimab administered intravenously every 14 days in combination with standard of care chemotherapy modified FOLFIRINOX.; Other Names: ADC-1013, JNJ-64457107

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Anti-drug-antibody (ADA) titer in serum (tolerability)	Immunogenicity of mitazalimab	From first dose until 28-56 days after end of study treatment
Cmax of mitazalimab (pharmacokinetics)	Cmax derived from mitazalimab serum concentrations	From first dose until 28-56 days after end of study treatment
Tmax of mitazalimab (pharmacokinetics)	Tmax derived from mitazalimab serum concentrations	From first dose until 28-56 days after end of study treatment
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
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
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
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

Collaborators and Investigators

• Sponsor: Alligator Bioscience AB
• Collaborators: Theradex; 4Pharma Ltd.
• Investigators: Principal Investigator: Jean-Luc van Laethem, Prof. MD, Hospital Erasme; Study Director: Sumeet Ambarkhane, MD, Alligator Bioscience AB

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Estimated): February 28, 2024
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Irinotecan; Pancreatic ductal adenocarcinoma; Oxaliplatin; 5-Fluorouracil; Leucovorin; PDAC; mitazalimab; modified FOLFIRINOX; Chemotherapy, combination
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: A-20-1013-C-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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