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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II Open-Label, Three-Part, Dose-Finding and Separate Cohort Expansion Trial to Assess the Safety, Tolerability and Preliminary Efficacy of Repeated Doses of CLEVER-1 Antibody FP-1305, in Subjects With Advanced Solid Tumours

Conditions
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Cancer

Intervention / Treatment
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* Biological: FP-1305 (bexmarilimab)


Participation Criteria
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Eligibility Criteria
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Subjects must meet all of the following inclusion criteria to be eligible for participation in the clinical trial: 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 ECOG performance status 0 or 1 Measurable disease in Parts II and III Adequate bone marrow, liver and kidney function defined as Blood white blood cell ≥ lower limit of normal Blood neutrophil count ≥ 1x10(9)/L Blood platelet count ≥ 100x10(9)/L, for HCC ≥ 50x10(9)/L Blood haemoglobin ≥ 9.0 g/dL Creatinine clearance > 40 mL/min calculated by Cockcroft-Gault formula AST ≤ 3 X ULN (≤ 5 x ULN when HCC or hepatic metastases are present) ALT ≤ 3 X ULN (≤ 5 x ULN when HCC or hepatic metastases present) Bilirubin ≤ 1.5 X ULN Albumin ≥ 3.0 g/dL The most recent measurements taken during the screening period must be within the required limits for the patient to be considered eligible (i.e. criteria met once during the screening period are not sufficient if there are more recent measurements available that are not within the required limits. It is however acceptable to repeat measurements if the initial measurements or subsequent measurements taken during the screening period are not within the required limits; the patient is eligible providing that the newest measurements are within the required limits). However, once a subject is out of the screening period, and has had eligibility confirmed and been enrolled, the pre-dose laboratory assessments are not subjected to inclusion criteria limits, but only for investigators assessment of subject safety. Women of child-bearing potential must have a negative pregnancy test in serum prior to trial entry 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; 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 Subjects in dialysis Use of Live (attenuated) vaccines for 30 days prior to the start of study treatment, during treatment, and until last visit Subject is unwilling or unable to comply with treatment and trial instructions Subjects with known hypersensitivity to the IMP or any of the pharmaceutical ingredients Specific Additional Exclusion Criteria for Hepatobiliary Cancers 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) Hepatic encephalopathy Ascites refractory to diuretic therapy Child-Pugh score ≥ 7

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose-escalation, six dose levels
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FP-1305 (bexmarilimab) 0.3 mg/kg<br>Part I, Dose-escalation FP-1305 0.3 mg/kg is administered in Q3W intervals | Biological: FP-1305 (bexmarilimab)<br>* 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.<br>* Other names: bexmarilimab;|
| Experimental: FP-1305 (bexmarilimab) 1 mg/kg<br>Part I and II, Dose-escalation FP-1305 1 mg/kg is administered in Q3W, Q2W or Q1W intervals | Biological: FP-1305 (bexmarilimab)<br>* 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.<br>* Other names: bexmarilimab;|
| Experimental: FP-1305 (bexmarilimab) 3 mg/kg<br>Part I and II, Dose-escalation FP-1305 3 mg/kg is administered in Q3W, Q2W or Q1W intervals | Biological: FP-1305 (bexmarilimab)<br>* 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.<br>* Other names: bexmarilimab;|
| Experimental: FP-1305 (bexmarilimab) 10 mg/kg<br>Part I and II, Dose-escalation FP-1305 10 mg/kg is administered in Q3W, Q2W or Q1W intervals | Biological: FP-1305 (bexmarilimab)<br>* 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.<br>* Other names: bexmarilimab;|
| Experimental: FP-1305 (bexmarilimab) 0.1 mg/kg<br>Part I Dose-escalation FP-1305 0.1 mg/kg is administered in three-week intervals | Biological: FP-1305 (bexmarilimab)<br>* 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.<br>* Other names: bexmarilimab;|
| Experimental: FP-1305 (bexmarilimab) 30 mg/kg<br>Part II Dose-escalation FP-1305 30 mg/kg is administered in Q3W, Q2W or Q1W intervals | Biological: FP-1305 (bexmarilimab)<br>* 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.<br>* Other names: bexmarilimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Incidence of 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. | Up to six years | 
| The response (ORR, CBR and irORR) to the treatment. | The objective response rate (ORR), clinical benefit rate (CBR) and immune-related ORR (irORR) 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 will be reported separately. | Up to six years |