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

Sponsor

Alligator Bioscience AB (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04888312

Collaborator

Theradex (Industry), 4Pharma Ltd. (Industry)

Enrollment

Locations

Arm

47.4

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Ductal Adenocarcinoma	Biological: CD40 agonist mitazalimab in combination with chemotherapy	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 17, 2021

Anticipated Primary Completion Date :

Feb 28, 2024

Anticipated Study Completion Date :

Aug 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Incidence of Dose Limiting Toxicities (DLTs) (Part 1: Phase 1b Dose escalation) [From first dose to end of dose limiting toxicity period (Day 1-21)]
Number of patients experiencing DLTs
Objective response rate (ORR) (Part 2: Phase 2 Dose expansion) [From first dose to 28-56 days after end of study treatment]
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 [From informed consent signed to 28-56 days after end of of study treatment]
Number of patients experiencing AEs. Number of events summarized by SOC and preferred term.
Anti-drug-antibody (ADA) titer in serum (tolerability) [From first dose until 28-56 days after end of study treatment]
Immunogenicity of mitazalimab
Cmax of mitazalimab (pharmacokinetics) [From first dose until 28-56 days after end of study treatment]
Cmax derived from mitazalimab serum concentrations
Tmax of mitazalimab (pharmacokinetics) [From first dose until 28-56 days after end of study treatment]
Tmax derived from mitazalimab serum concentrations
AUC(0-T) of mitazalimab (pharmacokinetics) [From first dose until 28-56 days after end of study treatment]
AUC(0-T) derived from mitazalimab serum concentrations
Anti-tumor Activity per RECIST 1.1 guideline (efficacy) [From first dose until 28-56 days after end of study treatment]
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) [From first dose and up to 2 years after end of study treatment]
Number of days from first dose of mitazalimab to progressive disease or death.
Overall survival (efficacy) [From first dose and up to 2 years after end of study treatment]
Number of days from first dose of mitazalimab until death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Cliniques Universitaires St-Luc	Brussels	Belgium
2	Hospital Erasme	Bruxelles	Belgium
3	Grand Hôpital de Charleroi	Charleroi	Belgium
4	UZA Antwerp	Edegem	Belgium
5	Universitair Ziekenhuis Gent	Gent	Belgium	9000
6	Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque,	Bordeaux	France
7	Centre Lyon Berard	Lyon	France
8	Institut Paoli-Calmettes	Marseille	France
9	Hopital Européen Georges Pompidou	Paris	France	75015
10	Institute de Cancérologie de l'Ouest	Saint-Herblain	France
11	Institute de Cancérologie de Lorraine	Vandœuvre-lès-Nancy	France
12	Hospital Universitario Vall d'Hebron, Barcelona, Spain	Barcelona	Spain
13	Hospital Universitario La Paz, Madrid, Spain	Madrid	Spain
14	Hospital Universitario Ramon y Cajal, Madrid, Spain	Madrid	Spain
15	Hospital Universitario Virgen del Rocio, Sevilla, Spain	Sevilla	Spain
16	Hospital Universitario Miguel Servet, Zaragoza, Spain	Zaragoza	Spain