Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients

Metastatic Pancreatic Ductal Adenocarcinoma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04888312
• Other study ID #: A-20-1013-C-03
• Status: Recruiting
• Phase: Phase 1/Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Ductal Adenocarcinoma

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