A Study to Evaluate Safety, Tolerability and Preliminary Efficacy of FP-1305 in Cancer Patients (MATINS)

NCT ID: NCT03733990

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-03
• Study Completion Date: 2023-10-31

Brief Summary

This is a first in human study to identify whether FP-1305 is suitable to use in humans. The previous pre-clinical studies have demonstrated that FP-1305 binds to a receptor known as CLEVER-1. CLEVER-1 has been shown to support tumour growth. No significant adverse events were witnessed in primates and the dose used will be 300 fold lower than the dose provided to primates which showed no toxicity.

The patients with advanced melanoma, uveal melanoma, cholangiocarcinoma, gallbladder cancer, ER+ breast, gastric, ovarian, pancreatic, colorectal, liver or anaplastic thyroid cancer who have exhausted all licenced therapeutic options will die due to their disease. Based on the investigator's existing data CLEVER-1 is expressed in these tumour types. Inhibition of CLEVER-1 with FP-1305 may have an anti-tumour effect in these patients.

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FP-1305 (bexmarilimab) 0.3 mg/kg

Part I, Dose-escalation FP-1305 0.3 mg/kg is administered in Q3W intervals

Group Type: EXPERIMENTAL

FP-1305 (bexmarilimab)

Intervention Type: BIOLOGICAL

The study will test for the first time in patients with cancer, an experimental medicine, called FP-1305. The study goal is to find the dose of FP-1305 that works best against cancer while it remains safe for use, tolerable and effective in patients with cancer.

FP-1305 (bexmarilimab) 1 mg/kg

Part I and II, Dose-escalation FP-1305 1 mg/kg is administered in Q3W, Q2W or Q1W intervals

Group Type: EXPERIMENTAL

FP-1305 (bexmarilimab)

Intervention Type: BIOLOGICAL

The study will test for the first time in patients with cancer, an experimental medicine, called FP-1305. The study goal is to find the dose of FP-1305 that works best against cancer while it remains safe for use, tolerable and effective in patients with cancer.

FP-1305 (bexmarilimab) 3 mg/kg

Part I and II, Dose-escalation FP-1305 3 mg/kg is administered in Q3W, Q2W or Q1W intervals

Group Type: EXPERIMENTAL

FP-1305 (bexmarilimab)

Intervention Type: BIOLOGICAL

The study will test for the first time in patients with cancer, an experimental medicine, called FP-1305. The study goal is to find the dose of FP-1305 that works best against cancer while it remains safe for use, tolerable and effective in patients with cancer.

FP-1305 (bexmarilimab) 10 mg/kg

Part I and II, Dose-escalation FP-1305 10 mg/kg is administered in Q3W, Q2W or Q1W intervals

Group Type: EXPERIMENTAL

FP-1305 (bexmarilimab)

Intervention Type: BIOLOGICAL

The study will test for the first time in patients with cancer, an experimental medicine, called FP-1305. The study goal is to find the dose of FP-1305 that works best against cancer while it remains safe for use, tolerable and effective in patients with cancer.

FP-1305 (bexmarilimab) 0.1 mg/kg

Part I Dose-escalation FP-1305 0.1 mg/kg is administered in three-week intervals

Group Type: EXPERIMENTAL

FP-1305 (bexmarilimab)

Intervention Type: BIOLOGICAL

The study will test for the first time in patients with cancer, an experimental medicine, called FP-1305. The study goal is to find the dose of FP-1305 that works best against cancer while it remains safe for use, tolerable and effective in patients with cancer.

FP-1305 (bexmarilimab) 30 mg/kg

Part II Dose-escalation FP-1305 30 mg/kg is administered in Q3W, Q2W or Q1W intervals

Group Type: EXPERIMENTAL

FP-1305 (bexmarilimab)

Intervention Type: BIOLOGICAL

The study will test for the first time in patients with cancer, an experimental medicine, called FP-1305. The study goal is to find the dose of FP-1305 that works best against cancer while it remains safe for use, tolerable and effective in patients with cancer.

Interventions

FP-1305 (bexmarilimab)

The study will test for the first time in patients with cancer, an experimental medicine, called FP-1305. The study goal is to find the dose of FP-1305 that works best against cancer while it remains safe for use, tolerable and effective in patients with cancer.

Intervention Type: BIOLOGICAL

Other Intervention Names

bexmarilimab

Eligibility Criteria

Inclusion Criteria

1. Written Informed Consent

2. Aged ≥ 18 years male or female

3. Tumour sample should be collected during screening period. If a recent tumour biopsy obtained within six months before the date of consent is available (or older, as agreed on a case by case basis with the sponsor), that may be used. At the discretion of the sponsor, the tumour sample may be optional for certain subjects in Part III

4. Life expectancy > 12 weeks

5. Histologically confirmed advanced (inoperable or metastatic) malignancies without standard therapeutic options available:

• Hepatocellular carcinoma
• Gallbladder cancer or intra- or extrahepatic cholangiocarcinoma
• Colorectal adenocarcinoma
• Serous poorly differentiated (Grade 3) ovarian adenocarcinoma or undifferentiated ovarian cancer
• Pancreatic ductal adenocarcinoma
• Immunotherapy (IO) refractory cutaneous melanoma (progression either on or after programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) or cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody therapy)
• Uveal melanoma in Parts II and III
• Gastric adenocarcinoma (including adenocarcinoma of the distal esophagus / GE junction) in Parts II and III
• ER+ breast cancer in Parts II and III
• Anaplastic thyroid cancer in Parts II and III

6. ECOG performance status 0 or 1

7. Measurable disease in Parts II and III

9. Women of child-bearing potential must have a negative pregnancy test in serum prior to trial entry

10. Women of child-bearing potential and men who have partners of child-bearing potential must be willing to practise highly effective contraception for the duration of the trial and for three months after the completion of treatment

Exclusion Criteria

1. Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than five half-lives from a small molecule targeted therapy or oral anticancer chemotherapy before the first IMP administration

2. Any immunotherapy within preceding 6 weeks from the first IMP administration

3. Investigational therapy or major surgery within 4 weeks from the date of consent

4. Active clinically serious infection > Grade 2 NCI-CTCAE version 5.0 (Appendix 5 - Common Toxicity Criteria Gradings) within preceding 2 weeks from the date of consent

5. Brain metastases

6. Subject has not recovered from the previous therapies to Grade ≤ 1 severity as classified by the NCI-CTCAE version 5.0 (except Grade ≤ 2 alopecia, neuropathy or thyroid disorders)

7. Pregnant or lactating women

8. History of second malignancy except for non-melanotic skin cancer, cervical carcinoma in situ or superficial bladder cancer, or any other malignancy treated previously with curative intent and more than three years without relapse

9. Evidence of severe or uncontrolled systemic diseases, congestive cardiac failure New York Heart Association (NYHA) class 2 (Appendix 7 - NYHA classification), Myocardial Infarction (MI) within 6 months or laboratory finding that in the view of the investigator makes it undesirable for the subject to participate in the trial

10. Any medical condition that the Investigator considers significant to compromise the safety of the subject or that impairs the interpretation of IMP toxicity assessment

11. Confirmed human immunodeficiency virus infection

12. Symptomatic cytomegalovirus infection

13. Subjects with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia)

14. The subject requires systemic corticosteroid or other immunosuppressive treatment

15. Subjects with organ transplants

16. Subjects in dialysis

17. Use of Live (attenuated) vaccines for 30 days prior to the start of study treatment, during treatment, and until last visit

18. Subject is unwilling or unable to comply with treatment and trial instructions

19. Subjects with known hypersensitivity to the IMP or any of the pharmaceutical ingredients

1. Any ablative therapy (Radio Frequency Ablation or Percutaneous Ethanol Injection) for HCC (this should not exclude subjects if target lesion(s) have not been treated and occurred > 6 weeks prior trial entry)

2. Hepatic encephalopathy

3. Ascites refractory to diuretic therapy

4. Child-Pugh score ≥ 7

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

Sponsors

Faron Pharmaceuticals Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Petri Bono, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Terveystalo Ltd

Locations

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Clinical Research Institute HUCH Ltd

Helsinki, , Finland

Oulu University Hospital

Oulu, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Hospital

Turku, , Finland

The Institut Gustave Roussy

Villejuif, , France

Erasmus University Medical Center Rotterdam

Rotterdam, , Netherlands

START Madrid - CIOCC Hospital HM Sanchinarro

Madrid, , Spain

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

Queen Elizabeth Hospital Birmingham

Birmingham, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; Finland; France; Netherlands; Spain; United Kingdom

References

Rannikko JH, Verlingue L, de Miguel M, Pasanen A, Robbrecht D, Skytta T, Iivanainen S, Shetty S, Ma YT, Graham DM, Arora SP, Jaakkola P, Yap C, Xiang Y, Mandelin J, Karvonen MK, Jalkanen J, Karaman S, Koivunen JP, Minchom A, Hollmen M, Bono P. Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial. Cell Rep Med. 2023 Dec 19;4(12):101307. doi: 10.1016/j.xcrm.2023.101307. Epub 2023 Dec 5.

Reference Type: DERIVED

PMID: 38056464 (View on PubMed)

Hollmen M, Maksimow M, Rannikko JH, Karvonen MK, Vainio M, Jalkanen S, Jalkanen M, Mandelin J. Nonclinical Characterization of Bexmarilimab, a Clever-1-Targeting Antibody for Supporting Immune Defense Against Cancers. Mol Cancer Ther. 2022 Jul 5;21(7):1207-1218. doi: 10.1158/1535-7163.MCT-21-0840.

Reference Type: DERIVED

PMID: 35500016 (View on PubMed)

Virtakoivu R, Rannikko JH, Viitala M, Vaura F, Takeda A, Lonnberg T, Koivunen J, Jaakkola P, Pasanen A, Shetty S, de Jonge MJA, Robbrecht D, Ma YT, Skytta T, Minchom A, Jalkanen S, Karvonen MK, Mandelin J, Bono P, Hollmen M. Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors: Results from a Phase I/II Clinical Trial. Clin Cancer Res. 2021 Aug 1;27(15):4205-4220. doi: 10.1158/1078-0432.CCR-20-4862. Epub 2021 Jun 2.

Reference Type: DERIVED

PMID: 34078651 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002732-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FP2CLI001

Identifier Type: -

Identifier Source: org_study_id