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

• ClinicalTrials.gov Identifier: NCT03733990
• Recruitment Status: Recruiting
• First Posted: November 7, 2018
• Last Update Posted: November 23, 2020
• Sponsor: Faron Pharmaceuticals Ltd
• Information provided by (Responsible Party): Faron Pharmaceuticals Ltd

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cancer	Biological: FP-1305	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 650 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Dose-escalation, five dose levels
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 3, 2018
• Estimated Primary Completion Date: November 30, 2024
• Estimated Study Completion Date: November 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: FP-1305 0.3 mg/kg; Part I/ Dose-escalation FP-1305 0.3 mg/kg is administered in three-week intervals	Biological: FP-1305; 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.
Experimental: FP-1305 1 mg/kg; Part I, Dose-escalation FP-1305 1 mg/kg is administered in three-week intervals	Biological: FP-1305; 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.
Experimental: FP-1305 3 mg/kg; Part I, Dose-escalation FP-1305 3 mg/kg is administered in three-week intervals	Biological: FP-1305; 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.
Experimental: FP-1305 10 mg/kg; Part I, Dose-escalation FP-1305 10 mg/kg is administered in three-week intervals	Biological: FP-1305; 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.
Experimental: FP-1305 0.1 mg/kg; Part I/ Dose-escalation FP-1305 0.1 mg/kg is administered in three-week intervals	Biological: FP-1305; 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.

Outcome Measures

Primary Outcome Measures :

1. Dose limiting toxicities (DLT) in the trial subjects. [ Time Frame: Up to one year ]
   Tolerable dose(s) will be determined by the TITE-CRM based on the occurrence/non-occurrence of dose limiting toxicities in the trial subjects.
2. Incidence of Treatment - Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to six years ]
   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.
3. CLEVER-1 positivity in the tumour. [ Time Frame: Up to six years ]
   CLEVER-1 in tumour sample prior to treatment will be identified with immunohistochemistry and reported as positive cells / mm2 of sample.
4. The objective response rate (ORR) of the treatment. [ Time Frame: Up to six years ]
   The objective response rate (ORR) to the treatment will be determined by tumour imaging (tumor size) according to RECIST v.1.1. ORR will be reported as the proportion of subjects of all evaluable subjects.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in the clinical trial:

1. Written Informed Consent
2. Aged ≥ 18 years male or female
3. Recent (less than six months old from the date of consent) tumour sample obtained for biomarker analysis in Parts I and II (optional 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
8. 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.
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 those treated with curative intent more than three years previously without relapse and non-melanotic skin cancer, cervical carcinoma in situ or superficial bladder cancer
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

Specific Additional Exclusion Criteria for Hepatobiliary Cancers

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

Contacts and Locations

Contacts

Contact: Matti Karvonen, MD, PhD; 02 469 5151 ext 358; matti.karvonen@faron.com

Contact: Jarna Hannukainen, PhD; 02 469 5151 ext 358; jarna.hannukainen@faron.com

Locations

United States, Texas

The University of Texas Health Science Center at San Antonio; Recruiting

San Antonio, Texas, United States, 78229-3901

Contact: Sukeshi Patel Arora, MD, PhD

Finland

Clinical Research Institute HUCH Ltd; Recruiting

Helsinki, Finland, 00290

Contact: Annika Pasanen, MD, PhD

Oulu University Hospital; Recruiting

Oulu, Finland, 90220

Contact: Sanna Iivanainen, MD, PhD

Tampere University Hospital; Recruiting

Tampere, Finland, 33520

Contact: Tanja Skyttä, MD, PhD

France

The Institut Gustave Roussy; Recruiting

Villejuif, France, 94805

Contact: Christophe Massard, MD, PhD

Netherlands

Erasmus University Medical Center Rotterdam; Recruiting

Rotterdam, Netherlands, 3015 GD

Contact: Maja deJonge, MD, PhD

Spain

START Madrid - CIOCC Hospital HM Sanchinarro; Recruiting

Madrid, Spain, 28050

Contact: María José de Miguel, MD, PhD

United Kingdom

The Royal Marsden NHS Foundation Trust; Recruiting

Sutton, Surrey, United Kingdom, SM2 5PT

Contact: Anna Minchom, MD, PhD

Queen Elizabeth Hospital Birmingham; Recruiting

Birmingham, United Kingdom, B15 2GW

Contact: Yuk Ting Ma, MD, PhD

The Christie NHS Foundation Trust; Recruiting

Manchester, United Kingdom, M20 4BX

Contact: Donna Graham, MD, PhD

Sponsors and Collaborators

Faron Pharmaceuticals Ltd

Investigators

• Principal Investigator: Petri Bono, MD, PhD; Terveystalo Ltd

More Information

• Responsible Party: Faron Pharmaceuticals Ltd
• ClinicalTrials.gov Identifier: NCT03733990
• Other Study ID Numbers: FP2CLI001; 2018-002732-24 ( EudraCT Number )
• First Posted: November 7, 2018
• Last Update Posted: November 23, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No