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

NCT ID: NCT04888312

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-17
• Study Completion Date: 2026-06-30

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.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CD40 agonist mitazalimab in combination with chemotherapy

Intervention Type: BIOLOGICAL

Mitazalimab administered intravenously every 14 days in combination with standard of care chemotherapy modified FOLFIRINOX.

Interventions

CD40 agonist mitazalimab in combination with chemotherapy

Mitazalimab administered intravenously every 14 days in combination with standard of care chemotherapy modified FOLFIRINOX.

Intervention Type: BIOLOGICAL

Other Intervention Names

ADC-1013, JNJ-64457107

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alligator Bioscience AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yago Pico de Coaña, PhD

Role: STUDY_DIRECTOR

Alligator Bioscience AB

Jean-Luc van Laethem, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Erasme

Locations

Cliniques Universitaires St-Luc

Brussels, , Belgium

Hospital Erasme

Brussels, , Belgium

UZA Antwerp

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

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 Lorraine

Vandœuvre-lès-Nancy, , France

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

Seville, , Spain

Hospital Universitario Miguel Servet, Zaragoza, Spain

Zaragoza, , Spain

Countries

Belgium; France; Spain

References

Van Laethem JL, Geboes K, Borbath I, Macarulla Mercade T, Lambert A, Cassier P, Prenen H, Mitry E, Blanc JF, Pilla L, Feliu J, Rodriguez Garrote M, Pazo-Cid RA, Gallego I, Smith KE, Nordbladh K, Jimenez DG, Ellmark P, Pico de Coana Y, Ambarkhane SV, Beatty GL, O'Reilly EM. CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1. Cell Rep Med. 2025 Oct 7:102407. doi: 10.1016/j.xcrm.2025.102407. Online ahead of print.

Reference Type: DERIVED

PMID: 41061701 (View on PubMed)

Van Laethem JL, Borbath I, Prenen H, Geboes KP, Lambert A, Mitry E, Cassier PA, Blanc JF, Pilla L, Batlle JF, Garrote MR, Pazo-Cid RA, Gallego I, Smith KE, Ellmark P, Pico de Coana Y, Ambarkhane SV, Macarulla T. Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study. Lancet Oncol. 2024 Jul;25(7):853-864. doi: 10.1016/S1470-2045(24)00263-8. Epub 2024 Jun 1.

Reference Type: DERIVED

PMID: 38834087 (View on PubMed)

Other Identifiers

A-20-1013-C-03

Identifier Type: -

Identifier Source: org_study_id