IRB Study Number 24-967
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
• Evaluate the safety, tolerability, and dosimetry of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
• Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053
• Determine the effect of predose administration of varying doses of FPI-2053 on the radiation dosimetry of [111In]-FPI-2107 (whole body, organs, and selected regions of interest)
• Estimate the effect of predose administration of varying doses of FPI-2053 on the radiation dosimetry of [225Ac]-FPI-2068 (whole body, organs, and selected regions of interest)
Secondary Objectives
• Assess preliminary anti-tumour activity of [225Ac]-FPI-2068
• Obtain preliminary data on the tumour uptake of [111In]-FPI-2107
• Determine the PK of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068, and the effect of predose administration of varying doses of FPI-2053 on the PK of [111In]-FPI-2107 and [225Ac]-FPI-2068
• To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053
Inclusion Criteria
Informed Consent
Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this CSP.
Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, and analyses.
Age
- Must be 18 years of age or older at the time of signing the ICF.
Type of Participant and Disease Characteristics
- Histologically and/or cytologically confirmed solid tumour (either HNSCC, PDAC, CRC, NSCLC, GC, or RCC) that is metastatic or locally advanced and:
a. For treatment intent participants - inoperable (where surgery is not indicated due to disease extension, comorbidities, or other technical reasons) or recurrent.
b. For imaging only participants - determined to be clinically stable as per investigator assessment in the absence of concomitant anti-cancer therapy.
Moved to additional criteria (Section 5.3) as part of CSP V04.
For treatment intent participants only – Disease that has progressed despite prior treatment, and for which additional effective standard of care therapy is not available or is contraindicated, not tolerable, or the participant refuses standard therapy.
Measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Able to provide tumour tissue for analysis. If archival tissue obtained within the last 24 months is not available, a fresh biopsy will be requested for immunohistochemistry (IHC) and biomarker analyses. If a participant is unable to provide sufficient tumour tissue, they may still be considered eligible following discussion with the Medical Monitor. Availability of tissue must be confirmed prior to administration of FPI-2053 or [111In]-FPI-2107; however, the participant may receive study treatment prior to any analysis of the tissue.
Adequate organ function as indicated by the following laboratory values (all laboratory tests must be performed within 14 days prior to the first dose of investigational agent):
a) Haematological:
i. *Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 × 109/L)
ii. *Platelet count ≥ 100,000/mm3 (≥ 100 × 109/L)
iii. *Haemoglobin ≥ 9.0 g/dL (≥ 90 g/L)
iv. International normalised ratio 0.8 to upper limit of normal (ULN) or ≤ 3 for
participants receiving anticoagulant therapy such as coumadin or heparin
*Haematological criteria cannot be met with ongoing or recent blood transfusions (within 7 days prior to the scheduled first dose of study treatment) or require growth factor support (within 21 days prior to the scheduled first dose of study treatment).
b) Cardiac:
i. Resting QTcF: ≤ 450 msec for men and ≤ 470 msec for women
c) Renal:
i. Creatinine clearance ≥ 60 mL/min/1.73 m2 (calculated by Cockcroft-Gault formula)
d) Hepatic:
i. AST and ALT ≤ 3.0 × ULN (≤ 5 × ULN in participants with known liver metastasis)
ii. Serum total bilirubin ≤ 1.5 × ULN (≤ 3 x ULN in participants with Gilbert’s disease).
In the judgement of the Investigator, the participant is expected to be compliant and have a high probability of completing the study.
Anticipated life expectancy ≥3 months.
Reproduction
- a) All women of childbearing potential (WCBP) must agree to use at least two forms of contraception, one of which must be a highly effective method, or agree to remain abstinent, for the duration of study participation and for 6 months following both [111In]-FPI-2107 and the final dose of [225Ac]-FPI2068 (if applicable). See Appendix C for definitions of highly effective forms of contraception and WCBP.
b) Male participants should be asked to avoid unprotected sex with women of childbearing potential for the duration of study participation and for 6 months following both [111In]-FPI-2107 and the final dose of [225Ac]-FPI-2068 (if applicable). The effects of [111In]-FPI-2107 and [225Ac]-FPI-2068 on spermatogenesis and fertility in humans are not known. Participants should avoid procreation for 6 months after completion of study treatment and should refrain from donating sperm from the start of dosing until 6 months after discontinuing study treatment. See Appendix C for definitions of effective forms of contraception.
c) All WCBP must have a negative pregnancy test result during screening and prior to all imaging ([111In]-FPI2107 ± FPI-2053) and treatment [225Ac]-FPI-2068 ± FPI-2053) timepoints.
Exclusion Criteria
Medical Conditions
1 As judged by the Investigator, any evidence of the malignancy which, in the Investigator's opinion, makes it undesirable for the participant to participate in the study.
2 Contraindications to or inability to perform the imaging procedures required in this study (e.g., inability to lay flat for the image acquisitions, etc.).
3 Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (≥ once per month).
4 Previous or concurrent cancer that is distinct from the cancer under investigation in primary site or histology, except cervical carcinoma in situ, treated cutaneous basal cell carcinoma or squamous cell carcinoma, and superficial bladder tumours. Any cancer curatively treated >2 years prior to the first dose of [111In]-FPI-2107 is permitted.
5 History of organ transplantation, including stem cell transplantation; or prior treatment with chronic immunosuppressants.
6 History of myocardial infarction or New York Heart Association Class II-IV congestive heart failure within 6 months of the administration of the first dose of [111In]-FPI-2107), Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or worse conduction defect (e.g., right or left bundle branch block) or uncontrolled hypertension.
7 Concurrent severe and/or uncontrolled illness not related to cancer and/or social situation that would limit compliance with study requirements, including but not limited to:
a) Psychiatric illness, substance abuse
b) Serious chronic gastrointestinal conditions associated with diarrhoea.
c) Ongoing or active known infection, including HIV infection, hepatitis B or hepatitis C virus.
d) Has significant pulmonary dysfunction, including pneumonitis, interstitial lung disease (ILD), idiopathic pulmonary fibrosis, cystic fibrosis, or severe chronic obstructive pulmonary disease.
i. Has had a history of non-infectious ILD/pneumonitis that required oral or IV steroids, or supplemental oxygen. Participants with a history of radiation pneumonitis which has clinically and radiologically resolved and not requiring treatment with steroids may be eligible. The Investigator must carefully evaluate benefit-risk assessment on a case basis and discuss it with the Sponsor Study Physician prior to the participant's enrolment.
e) Diabetes mellitus with fasting serum glucose ≥ 160 mg/dL or random ≥ 250 mg/dL and glycated haemoglobin (HbA1c) > 8% (> 64 mmol/mol).
Prior/Concomitant Therapy
8 Prior systemic radiopharmaceutical therapy.
9 Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents within five half-lives or 4 weeks, whichever is shorter, prior to administration of the first dose of [111In]-FPI-2107:
a) Ongoing toxicities from prior treatment(s) must have resolved to ≤ CTCAE Grade 1, except for alopecia.
b) Concurrent systemic high-dose corticosteroids (in dosing exceeding 10 mg once a day of prednisone or equivalent) is excluded except when used intermittently in an antiemetic regimen, or as part of a premedication regimen.
10 External beam radiation therapy (EBRT) within 28 days prior to the first dose of [111In]-FPI-2107.
11 Major surgical procedure within 28 days prior to administration of the first dose of [111In]-FPI-2107.
12 *Received any type of vaccine (e.g., live, live-attenuated, killed, viral vector or messenger RNA [mRNA] vaccine) within 30 days prior to the first dose of FPI-2053 or [111In]-FPI-2107.
* Killed, viral vector, and mRNA vaccines may be allowed after completion of the DLT-period upon agreement between the Investigator, Sponsor, and Medical Monitor.
Prior/Concurrent Clinical Study Experience
13 Participation in another clinical study with an investigational product administered in the last 4 weeks or 5 half-lives, whichever is shorter.
14 Known or suspected allergies or contraindications to the Investigational Medicinal Product (IMP) or any component of the investigational drug formulation.
Diagnostic Assessments
15 Known untreated or active central nervous system (CNS) metastases and/or carcinomatous meningitis:
a) To be eligible for the study treatment, participants must have stable, well controlled disease for ≥ 1 month, as confirmed by magnetic resonance imaging (MRI) or CT scan, and CNS metastases must be well controlled by low dose steroids, anti-epileptics, or other symptom-relieving medications.
16 Clinically relevant proteinuria (e.g., urinary dipstick analysis for proteins is 3 + [300 mg/dL] or 4 + [1000 mg/dL], or daily urinary protein excretion > 500 mg).
Other Exclusions
17 Involvement in the planning and/or conduct of the study (applies to both Fusion Pharmaceuticals staff and/or staff at the study site).
18 Judgment by the Investigator that the participant should not take part in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
19 *Previous enrolment in the present study.
*Note that individuals who do not meet the criteria for participation in this study (general screen failure) may be rescreened. Only one general rescreening is allowed per participant in the study. Participants who complete imaging assessment but are not eligible for treatment will not be permitted to repeat the imaging screening, except imaging only participants who may be re-enrolled when their disease progresses if applicable.
20 Currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
