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

NCT03733990 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: FP2CLI0012018-002732-24
• Study Type: interventional
• Target: 216
• Locations: 6 countries
• Sites: 11

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

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicities (DLT) in the Trial Subjects.

  Tolerable dose(s) will be determined by the TITE-CRM based on the occurrence/non-occurrence of dose limiting toxicities in the trial subjects.

  Up to one year

• Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability)

  Number of adverse events and serious adverse events. Adverse events are collected, graded and reported according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

  approximately 4 years and 9 months

• The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1.

  The objective response rate (ORR) to the treatment will be determined by tumour imaging (tumor size) according to RECIST v.1.1. Results from each tumour type, dose level and dosing frequency are reported separately.

  approximately 4 years and 9 months

• The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1.

  The disease control rate (DCR) response to the treatment will be determined by tumour imaging (tumor size) according to RECIST v.1.1 are presented by cycles and by doing so there is no difference in the definition of DCR and Clinical Benefit Rate (CBR)

  approximately 4 years and 9 months

Study Arms (6)

FP-1305 (bexmarilimab) 0.3 mg/kg

EXPERIMENTAL

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

Biological: FP-1305 (bexmarilimab)

FP-1305 (bexmarilimab) 1 mg/kg

EXPERIMENTAL

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

Biological: FP-1305 (bexmarilimab)

FP-1305 (bexmarilimab) 3 mg/kg

EXPERIMENTAL

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

Biological: FP-1305 (bexmarilimab)

FP-1305 (bexmarilimab) 10 mg/kg

EXPERIMENTAL

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

Biological: FP-1305 (bexmarilimab)

FP-1305 (bexmarilimab) 0.1 mg/kg

EXPERIMENTAL

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

Biological: FP-1305 (bexmarilimab)

FP-1305 (bexmarilimab) 30 mg/kg

EXPERIMENTAL

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

Biological: FP-1305 (bexmarilimab)

Interventions

FP-1305 (bexmarilimab) 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.

Also known as: bexmarilimab

FP-1305 (bexmarilimab) 0.1 mg/kg; FP-1305 (bexmarilimab) 0.3 mg/kg; FP-1305 (bexmarilimab) 1 mg/kg; FP-1305 (bexmarilimab) 10 mg/kg; FP-1305 (bexmarilimab) 3 mg/kg; FP-1305 (bexmarilimab) 30 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent
• Aged ≥ 18 years male or female
• 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
• Life expectancy \> 12 weeks
• 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

You may not qualify if:

• 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
• Any immunotherapy within preceding 6 weeks from the first IMP administration
• Investigational therapy or major surgery within 4 weeks from the date of consent
• 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
• Brain metastases
• 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)
• Pregnant or lactating women
• 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
• 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
• Any medical condition that the Investigator considers significant to compromise the safety of the subject or that impairs the interpretation of IMP toxicity assessment
• Confirmed human immunodeficiency virus infection
• Symptomatic cytomegalovirus infection
• Subjects with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia)
• The subject requires systemic corticosteroid or other immunosuppressive treatment
• Subjects with organ transplants

Sponsors & Collaborators

• Faron Pharmaceuticals Ltd: lead

Study Sites (11)

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3901, United States

Location

Clinical Research Institute HUCH Ltd

Helsinki, 00290, Finland

Location

Oulu University Hospital

Oulu, 90220, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

The Institut Gustave Roussy

Villejuif, 94805, France

Location

Erasmus University Medical Center Rotterdam

Rotterdam, 3015 GD, Netherlands

Location

START Madrid - CIOCC Hospital HM Sanchinarro

Madrid, 28050, Spain

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Queen Elizabeth Hospital Birmingham

Birmingham, B15 2GW, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 38056464 DERIVED

• 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.

  PMID: 35500016 DERIVED

• 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.

  PMID: 34078651 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

bexmarilimab

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Faron Pharmaceuticals Ltd

info@faron.com

+35824695151

Study Officials

• Petri Bono, MD, PhD

  Terveystalo Ltd

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose-escalation, six dose levels

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: November 7, 2018
• Study Start: December 3, 2018
• Primary Completion: September 6, 2023
• Study Completion: October 31, 2023
• Last Updated: April 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); FI (4); US (1); FR (1); ES (1); NL (1)