Clinical trial NCT04888312: Safety and Efficacy of Mitazalimab in Combination with Chemotherapy in Pancreatic Cancer Patients
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
Keywords: mitazalimab
modified FOLFIRINOX
Pancreatic ductal adenocarcinoma
PDAC
Pancreatic Cancer
Chemotherapy, combination
5-Fluorouracil
Oxaliplatin
Leucovorin
Irinotecan
Lead sponsor: Alligator Bioscience AB
Sponsor class: INDUSTRY
Collaborators: name: Theradex
name: BC Platforms
First posted: 2021-05-17
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs) (Part 1: Phase 1b Dose escalation)
timeFrame: From first dose to end of dose limiting toxicity period (Day 1-21)
measure: Objective response rate (ORR) (Part 2: Phase 2 Dose expansion)
timeFrame: From first dose to 28-56 days after end of study treatment
Secondary outcomes:
measure: Type, frequency and severity of Adverse Events
timeFrame: From informed consent signed to 28-56 days after end of of study treatment
measure: Anti-drug-antibody (ADA) titer in serum (tolerability)
timeFrame: From first dose until 28-56 days after end of study treatment
measure: Cmax of mitazalimab (pharmacokinetics)
timeFrame: From first dose until 28-56 days after end of study treatment
measure: Tmax of mitazalimab (pharmacokinetics)
timeFrame: From first dose until 28-56 days after end of study treatment
measure: AUC(0-T) of mitazalimab (pharmacokinetics)
timeFrame: From first dose until 28-56 days after end of study treatment
measure: Anti-tumor Activity per RECIST 1.1 guideline (efficacy)
timeFrame: From first dose until 28-56 days after end of study treatment
measure: Progression free survival (efficacy)
timeFrame: From first dose and up to 2 years after end of study treatment
measure: Overall survival (efficacy)
timeFrame: From first dose and up to 2 years after end of study treatment
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Bruxelles
country: Belgium
facility: Hospital Erasme
city: Edegem
country: Belgium
facility: UZA Antwerp
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque,
city: Lyon
country: France
facility: Centre Lyon Berard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Paris
country: France
facility: Hopital Européen Georges Pompidou
city: Vandœuvre-lès-Nancy
country: France
facility: Institute de Cancérologie de Lorraine
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron, Barcelona, Spain
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Madrid, Spain
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal, Madrid, Spain
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio, Sevilla, Spain
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet, Zaragoza, Spain
Study officials:
affiliation: Alligator Bioscience AB
name: Sumeet Ambarkhane, MD
role: STUDY_DIRECTOR
affiliation: Hospital Erasme
name: Jean-Luc van Laethem, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: