Cancer
Conditions
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.
Interventions
BIOLOGICALFP-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.
Sponsors
Faron Pharmaceuticals Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose-escalation, six dose levels
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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. 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 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 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 Specific Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) in the Trial Subjects. | 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. |
| Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | approximately 4 years and 9 months | 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. |
| The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | approximately 4 years and 9 months | 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. |
| The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | approximately 4 years and 9 months | 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) |
Countries
Finland, France, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FP-1305 (Bexmarilimab) 0.3 mg/kg Part I, Dose-escalation FP-1305 0.3 mg/kg is administered in Q3W intervals
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. | 13 |
| 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
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. | 130 |
| 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
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. | 41 |
| 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
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. | 18 |
| FP-1305 (Bexmarilimab) 0.1 mg/kg Part I Dose-escalation FP-1305 0.1 mg/kg is administered in three-week intervals
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. | 5 |
| FP-1305 (Bexmarilimab) 30 mg/kg Part II Dose-escalation FP-1305 30 mg/kg is administered in Q3W, Q2W or Q1W intervals
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. | 9 |
| Total | 216 |
Baseline characteristics
| Characteristic | FP-1305 (Bexmarilimab) 0.3 mg/kg | FP-1305 (Bexmarilimab) 1 mg/kg | FP-1305 (Bexmarilimab) 3 mg/kg | FP-1305 (Bexmarilimab) 10 mg/kg | FP-1305 (Bexmarilimab) 0.1 mg/kg | FP-1305 (Bexmarilimab) 30 mg/kg | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 39 Participants | 16 Participants | 9 Participants | 2 Participants | 1 Participants | 77 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 91 Participants | 25 Participants | 9 Participants | 3 Participants | 8 Participants | 139 Participants |
| Age, Continuous | 67.15 years STANDARD_DEVIATION 5.444 | 59.67 years STANDARD_DEVIATION 10.563 | 61.80 years STANDARD_DEVIATION 11.023 | 61.44 years STANDARD_DEVIATION 13.321 | 57.60 years STANDARD_DEVIATION 16.95 | 57.33 years STANDARD_DEVIATION 6.69 | 60.53 years STANDARD_DEVIATION 10.787 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 18 Participants | 7 Participants | 5 Participants | 0 Participants | 1 Participants | 33 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 106 Participants | 33 Participants | 12 Participants | 5 Participants | 8 Participants | 174 Participants |
| Region of Enrollment Finland | 6 participants | 43 participants | 12 participants | 3 participants | 5 participants | 3 participants | 72 participants |
| Region of Enrollment France | 0 participants | 26 participants | 5 participants | 4 participants | 0 participants | 0 participants | 35 participants |
| Region of Enrollment Netherlands | 2 participants | 16 participants | 8 participants | 4 participants | 0 participants | 1 participants | 31 participants |
| Region of Enrollment Spain | 0 participants | 20 participants | 8 participants | 3 participants | 0 participants | 5 participants | 36 participants |
| Region of Enrollment United Kingdom | 5 participants | 21 participants | 8 participants | 3 participants | 0 participants | 0 participants | 37 participants |
| Region of Enrollment United States | 0 participants | 4 participants | 0 participants | 1 participants | 0 participants | 0 participants | 5 participants |
| Sex: Female, Male Female | 8 Participants | 60 Participants | 19 Participants | 6 Participants | 5 Participants | 6 Participants | 104 Participants |
| Sex: Female, Male Male | 5 Participants | 70 Participants | 22 Participants | 12 Participants | 0 Participants | 3 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 12 / 130 | 3 / 41 | 3 / 18 | 0 / 5 | 0 / 9 |
| other Total, other adverse events | 13 / 13 | 122 / 130 | 38 / 41 | 17 / 18 | 5 / 5 | 9 / 9 |
| serious Total, serious adverse events | 1 / 13 | 57 / 130 | 13 / 41 | 10 / 18 | 3 / 5 | 4 / 9 |
Outcome results
Primary
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.
Time frame: Up to one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FP-1305 (Bexmarilimab) 0.3 mg/kg | Dose Limiting Toxicities (DLT) in the Trial Subjects. | 0 DLT |
| FP-1305 (Bexmarilimab) 1 mg/kg | Dose Limiting Toxicities (DLT) in the Trial Subjects. | 0 DLT |
| FP-1305 (Bexmarilimab) 3 mg/kg | Dose Limiting Toxicities (DLT) in the Trial Subjects. | 0 DLT |
| FP-1305 (Bexmarilimab) 10 mg/kg | Dose Limiting Toxicities (DLT) in the Trial Subjects. | 0 DLT |
| FP-1305 (Bexmarilimab) 0.1 mg/kg | Dose Limiting Toxicities (DLT) in the Trial Subjects. | 0 DLT |
| FP-1305 (Bexmarilimab) 30 mg/kg | Dose Limiting Toxicities (DLT) in the Trial Subjects. | 0 DLT |
Primary
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.
Time frame: approximately 4 years and 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FP-1305 (Bexmarilimab) 0.3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 13 Participants |
| FP-1305 (Bexmarilimab) 1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 122 Participants |
| FP-1305 (Bexmarilimab) 3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 38 Participants |
| FP-1305 (Bexmarilimab) 10 mg/kg | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 17 Participants |
| FP-1305 (Bexmarilimab) 0.1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 5 Participants |
| FP-1305 (Bexmarilimab) 30 mg/kg | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | 9 Participants |
Primary
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)
Time frame: approximately 4 years and 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FP-1305 (Bexmarilimab) 0.3 mg/kg | The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 1 Participants |
| FP-1305 (Bexmarilimab) 1 mg/kg | The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 20 Participants |
| FP-1305 (Bexmarilimab) 3 mg/kg | The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 4 Participants |
| FP-1305 (Bexmarilimab) 10 mg/kg | The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 2 Participants |
| FP-1305 (Bexmarilimab) 0.1 mg/kg | The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 0 Participants |
| FP-1305 (Bexmarilimab) 30 mg/kg | The Disease Control Rate (DCR) Response to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 1 Participants |
Primary
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.
Time frame: approximately 4 years and 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FP-1305 (Bexmarilimab) 0.3 mg/kg | The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 1 Participants |
| FP-1305 (Bexmarilimab) 1 mg/kg | The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 0 Participants |
| FP-1305 (Bexmarilimab) 3 mg/kg | The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 0 Participants |
| FP-1305 (Bexmarilimab) 10 mg/kg | The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 0 Participants |
| FP-1305 (Bexmarilimab) 0.1 mg/kg | The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 0 Participants |
| FP-1305 (Bexmarilimab) 30 mg/kg | The Response Objective Response Rate (ORR) to the Treatment Was Planned to be Determined by Tumor Imaging According to RECIST 1.1. | 0 Participants |