MATINS
Research type
Research Study
Full 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.
IRAS ID
254302
Contact name
Shishir Shetty
Contact email
Sponsor organisation
Faron Pharmaceuticals Ltd
Eudract number
2018-002732-24
Duration of Study in the UK
6 years, 0 months, 0 days
Research summary
Research Summary
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.
In Part I, different doses will be given to individual participants to test the best dose. The first and the second study subject will get the lowest dose. Dose is raised step wise to the next study subjects once lower dose has been demonstrated safe. Two subjects are treated at each dose level. Each participant will continue the whole Part I in the same dose they have started the study. In Part II and III, all patients will receive the same dose, which is selected based on Part I. No patient will receive a placebo.
Summary of Results
CLEVER-1 is a protein that has been demonstrated to help tumours grow. Faron Pharmaceuticals Ltd are developing a study drug called FP-1305 which is an antibody for CLEVER-1. As an antibody, FP-1035 can block CLEVER-1 in the body and prevent tumours from growing.
The purpose of this study was to investigate the study drug FP-1305 in subjects with advanced solid tumours. This study was split into 3 parts and the overall objectives of this study were to determine the safety, tolerability (degree to which side effects of a drug can be tolerated) and preliminary efficacy (effectiveness) of FP-1305 in advanced solid tumours, following administration of doses of FP-1305.
1. In the first part of the study (Part 1, dose escalation), the dose was increased to determine the maximum tolerated dose (MTD [i.e., the highest dose of a drug or treatment that does not cause unacceptable side effects]).
2. The dose escalation part was followed by the second part (Part 2, dose expansion) to further test the selected dose(s) from Part 1 and explore new doses in special groups of predefined tumour types, and to investigate the tolerability, safety, pharmacokinetics (PK [i.e., the concentration of the drug in the blood]), pharmacodynamics (PD [i.e., what the drug does to the body]]) and preliminary efficacy of more frequent dosing.
3. Part 3 was planned to explore further doses of the Part 2 groups to demonstrate efficacy; however, after reviewing all the data, the Sponsor determined that sufficient safety and efficacy data from this study were available to achieve the objectives of this study and Part 3 of the study was not conducted.The study consisted of 216 subjects across the 2 parts of the study.
Assessments conducted to determine the efficacy of FP-1305 included:
• Tumour response to FP-1305 (including overall response, best response and duration of response); • Soluble CLEVER-1 (sCLEVER) assessment. CLEVER-1 is a protein that has been demonstrated to help tumours grow.
• Pro-inflammatory panel (biomarkers that are associated with the inflammatory response). The inflammatory response is one of the body's ways by which it attacks cancer cells).
• Chemokine panel (chemokines control the migration and positioning of immune cells in tissues).
• Flow cytometry (measurement of immune cells in the blood).
• Immunohistochemistry panel (to identify markers of cancer and the action of the immune system).Safety assessments were conducted, and blood samples were taken at set time points throughout the study to measure the amount of FP-1305 in the blood. Blood samples for antidrug antibodies (ADA [antibodies produced by the body in response to the drug which may inactivate the drug]) were collected.
The results of the safety assessments showed that FP-1305 was considered to be safe and well tolerated in subjects with advanced solid tumours across all dose strengths evaluated during the study (in once every 3 weeks, once every 2 weeks or once every week cycles at doses of 0.1, 0.3, 1.0, 3.0, 10 or 30 mg/kg). No dose limiting toxicities (side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment) were reported during the study. The majority of reported side effects were considered not related to the study drug and were mild or moderate in severity. There were no notable differences in the overall number of side effects related to the strength of the FP‑1305 dose. The most commonly occurring side effects were fatigue (extreme tiredness), anaemia (low levels of healthy red blood cells) and abdominal pain (stomach ache). The most commonly reported side effects that were considered related to study drug were fatigue, pyrexia (fever), nausea (feeling sick) and anaemia.
A total of 18 events related to the immune system were reported for 8 subjects, all of which were related to study drug and the majority of which were mild or moderate in severity.
Serious events are those that lead to death, are life-threatening, require inpatient hospitalization, or prolonged of existing hospitalization, result in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions and/or are a congenital anomaly/birth defect.
A total of 18 events that led to death of subjects were reported in the study, all of which were no considered related to FP-1305.
Overall, excluding serious events of disease progression that were not study drug related, 137 serious events were reported for 88 subjects, the majority of which were not related to FP-1305. A total of 17 serious events were related to FP-1305, of which only pyrexia was reported by more than 1 subject. A total of 5 serious events associated with hepatobiliary disorders (related to liver, bile ducts, and/or gallbladder) considered related to study drug were reported; however, the events were all single occurrences.
With respect to the other objectives of the study the following outcomes were reported:
• One (1) subject with colorectal cancer had an objective tumour response to the treatment. One (1) other subject had a partial tumour response in study.
• Subjects who had achieved complete response, partial response, and/or stable disease) were reported as having disease control rate. Disease control rate was recorded for 27/211 subjects (12.8%) as their best response by the 4th cycle of taking the drug and for 28/211 subjects (13.3%) by the 7th cycle of taking the drug.
• A total of 31 subjects (14.6%) had stable disease recorded as their best response to the treatment at any time in the study.
• There were positive changes in sCLEVER, proinflammatory panel, chemokine panel and measurement of immune cells in the blood after treatment with FP-1305. Subjects that had disease control rate recorded during the study had more positive results than subjects without disease control rate.
• An association between intratumoural CLEVER-1 and subjects having disease control was reported.
• The best results of the sCLEVER assessments after receiving FP1305 were recorded for those subjects that were treated with the 1.0 mg/kg and 3.0 mg/kg dose levels.
• The percentage of patients with FP-1305 antidrug antibodies (ADA) after receiving FP-1305 was recorded as 17.6% of evaluable patients. This was not considered related to the treatment safety or efficacy.
• Subjects with disease control rate survived for longer overall and also for longer without tumour progression compared to subjects without disease control rate. This difference was statistically significant, which means the results were unlikely to be by chance.
• The maximum concentrations of FP-1305 appeared to increase in a way which was proportional to the dose strength i.e. as the dose strength increased, so did the amount measured in blood samples. The amount of drug to which the body was exposed increased in a way which was more than proportional.
• The amount of FP-1305 measured in blood samples was compared between subjects who had been dosed with 1.0 mg/kg once every week and subjects who had been dosed with 1.0 mg/kg once every 3 weeks. There appeared to be no major differences in the amount of FP-1305 measured in blood samples between these subjects.In summary, the results of the study met the objectives of the study and allowed for the further clinical trials and investigations of FP-1305 for treatment of advanced solid tumours. The efficacy results of the study support using the 1.0 and 3.0 mg/kg doses for future studies.
REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
18/WM/0361
Date of REC Opinion
19 Dec 2018
REC opinion
Further Information Favourable Opinion