Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12625000361404
Ethics application status
Approved
Date submitted
15/02/2025
Date registered
24/04/2025
Date last updated
24/04/2025
Date data sharing statement initially provided
24/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to investigate safety and anti-tumour activity of a Fibroblast Activation Protein (FAP)-targeting radiotracer (177Lu-FO-004) in patients with advanced cancer.
Scientific title
A Phase 1, Multicentre, Open-label, Non-randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of 177Lu-FO-004 in Patients with advanced solid tumours.
Secondary ID [1] 313681 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced solid tumours 336255 0
Condition category
Condition code
Cancer 332799 332799 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study uses two Fibroblast Activation Protein (FAP)-targeting investigational products to diagnose (68Ga-3BP-3940) and treat (177Lu-FO-004) patients with advanced solid tumours.

Following enrolment, patients will receive 100-250 MBq 68Ga-3BP-3940 1 hour prior to a PET/CT scan. The intravenous bolus injection will be performed under the supervision of the study Investigator or appropriately qualified delegate. The dose range of 68Ga-3BP-3940 was selected taking into account clinical and manufacturing consideration related to the short 68-minute half-life of 68Ga, decay during transport between manufacturing site and the patient, and variable elution efficiencies associated with the lifecycle of the gallium generator. The injected dose is therefore expected to vary, and all injected activities within the stated range are supported by the non-clinical toxicology study data. To initiate treatment with 177Lu-FO-004, patients must be identified as having FAP-positive tumours.

The Study will be conducted in 2 parts sequentially:

Part 1 Dose escalation: Up to 30 patients will be grouped into up to 4 cohorts and receive up to 6 cycles of 177Lu-FO-004 administered intravenously at 6-week intervals. The starting dose is 3.7 GBq, with potential de-escalation to 1.85 GBq or escalation in increments for a total of 4 dose levels (5.55 GBq; 7.4 GBq; 9.25 GBq). After completion of the first cycle by at least 3 evaluable patients, the Sponsor will convene a meeting with the Dose Cohort Review Committee (DCRC). Patient data including, but not limited to, demographics, haematology, clinical chemistry, urinalysis, electrocardiogram (ECG) results, dose limiting toxicity (DLTs), adverse events (AEs)/serious AEs (SAEs), and dosimetry, for current and prior cohorts will be reviewed by the DCRC. Dosimetry data for review by the DCRC will be generated by a central reviewer. The observed DLT rate at the current dose level will be compared to the dose escalation/de-escalation rules outlined in a BOIN design. Based on the design rules and review of all relevant data, the DCRC will reach agreement on whether to escalate to the next dose level, to expand recruitment at the current dose level, or to reduce to a lower or intermediate dose level. The DCRC will not recommend dose escalation above the dose level recommended per the BOIN design. The DCRC may also decide to reduce the total number of doses for the current and/or previous cohorts based on available clinical and dosimetry data. Based on patient data, including safety and dosimetry data, the dosing interval may be altered. The above steps will be repeated until the maximum sample size of 30 is reached, or until the number of patients treated at the current dose reaches 12, or until the study is stopped before that for safety or other reasons, whichever occurs first.

Part 2 will be initiated after the most suitable recommended Phase 2 dose (RP2D) is identified based on safety, tolerability and efficacy.

Part 2 RP2D expansion: Up to 26 additional patients will receive up to 6 cycles of the RP2D at 6-week intervals to confirm safety and efficacy using the same dosing schema as in part 1. Up to 6 of these patients will undergo additional pharmacokinetic and ECG assessments. All patients will undergo SPECT/CT scans at 4 time points in Cycle 1 and on 2 occasions in subsequent cycles for dosimetry. All patients will have CT for disease assessment every 12 weeks for up to 2 years.
Intervention code [1] 330276 0
Diagnosis / Prognosis
Intervention code [2] 330277 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340321 0
To evaluate the safety and tolerability of 177Lu-FO-004.
Timepoint [1] 340321 0
Vital signs, physical examinations, ECGs, laboratory assessments, ECOG performance status, AEs, and SAEs will be assessed during enrolment. Additionally vital signs will be assessed, blood and urine samples for safety monitoring will be collected additionally on day 1, 8, 15 and 22 of Cycle 1, on day 1, 8 and 22 of Cycle 2, and on day 1 and 22 for cycle 3 onwards. Physical examination, ECG´s and ECOG performance status will be assessed at day 1 of each cycle. Whole blood for surrogate PK will be collected at following time windows in cycle 1: within 5 min before end of infusion (EOI) and 0.5 h (± 5 min); 1 h (± 10 min); 2 h (± 10 min); 3 h (± 10 min); 4 h (± 15 min); 24 h (± 4 h); 48, 72, or 96 h (± 4 h); and 168 h (± 4 h) post-infusion. From cycle 2 onwards samples will be collected within 5 min before EOI and 0.5 h (± 5 min); 1 h (± 10 min); 2 h (± 10 min); 3 h (± 10 min); 4 h (± 15 min); and 168 h (± 4 h) post-infusion. Total 48-hour urine will be collected from the start of infusion to 1 hour after infusion, 1 to 6 hours post-infusion, 6 to 12 hours post-infusion, 12 to 24 hours post-infusion, 24 to 36 hours post-infusion, and 36 to 48 hours post-infusion. Adverse events will be continuously monitored until 2 years after enrolment.
Secondary outcome [1] 443712 0
To measure the radiation dosimetry of 177Lu-FO-004.
Timepoint [1] 443712 0
Dosimetry is performed after each SPECT/CT scan in cycle 1 on days 1, 2, 3 (or 4 or 5), 8 and days 1 and 8 from cycle 2 onwards.
Secondary outcome [2] 443716 0
To evaluate the safety of 68Ga-3BP-3940.
Timepoint [2] 443716 0
Safety of 68Ga-3BP-3940 will be evaluated up to the end of PET/CT Imaging.
Secondary outcome [3] 443714 0
To evaluate the pharmacokinetics (PK) of 177Lu-FO-004.
Timepoint [3] 443714 0
Whole blood will be collected from all patients in cycle 1 at following time points: within 5 min before end of infusion (EOI) and 0.5 h (± 5 min); 1 h (± 10 min); 2 h (± 10 min); 3 h (± 10 min); 4 h (± 15 min); 24 h (± 4 h); 48, 72, or 96 h (± 4 h); and 168 h (± 4 h) post-infusion. From cycle 2 onwards samples will be collected within 5 min before EOI and 0.5 h (± 5 min); 1 h (± 10 min); 2 h (± 10 min); 3 h (± 10 min); 4 h (± 15 min); and 168 h (± 4 h) post-infusion. Plasma PK samples will be collected at the same time points as for the whole blood samples only in cycle 1 of Part 2 (the RP2D Expansion PK Cohort). Total 48-hour urine will be collected from the start of infusion to 1 hour after infusion, 1 to 6 hours post-infusion, 6 to 12 hours post-infusion, 12 to 24 hours post-infusion, 24 to 36 hours post-infusion, and 36 to 48 hours post-infusion.
Secondary outcome [4] 443715 0
To evaluate preliminary activity of 177Lu-FO-004 in advanced solid tumours.
Timepoint [4] 443715 0
Tumour assessments will be performed at screening and at the end of every 6 weeks relative to the first dose of 177Lu-FO-004 during the treatment phase. Additionally, all participants will also have CT scans every 12 weeks for up to 2 years during the long-term Follow-up phase.
Secondary outcome [5] 443713 0
To determine tumour uptake using 68Ga-3BP-3940.
Timepoint [5] 443713 0
After enrolment the 68Ga-3BP-3940 imaging has to be completed (at least 5 days before start of treatment period).

Eligibility
Key inclusion criteria
1. Individuals must have adequate organ function within the screening period, including bone marrow, liver and renal function.
2. Individuals must have an adequate Eastern Cooperative Oncology Group (ECOG).
3. Individuals must have a life expectancy of at least 6 months.
4. Individuals must have measurable disease per RECIST v1.1.
5. Individuals must have a histologically and/or cytologically confirmed advanced/metastatic solid tumour.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active second malignancy.
2. Received anticancer treatment for CNS metastases or prior radiopharmaceutical therapy within 14 days (within 28 days for checkpoint inhibitor and other antibody therapies).
3. Received prior therapy targeting FAP.
4. Unable to tolerate CT scans with contrast and/or PET scans.
5. Infection requiring systemic antibiotics within 2 weeks prior to administration of 177Lu-FO-004.
6. Impaired cardiac function or clinically significant cardiac diseases.
7. Female patients being pregnant or breast feeding.
8. Significant weight loss (>10% of body weight) within 28 days prior to providing informed consent for this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
9/05/2025
Actual
Date of last participant enrolment
Anticipated
10/04/2028
Actual
Date of last data collection
Anticipated
17/01/2030
Actual
Sample size
Target
56
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA,VIC
Recruitment hospital [1] 27463 0
Icon Integrated Cancer Centre North Lakes - North Lakes
Recruitment hospital [2] 27465 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 27464 0
GenesisCare - Murdoch - Murdoch
Recruitment hospital [4] 27466 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 43574 0
4509 - North Lakes
Recruitment postcode(s) [2] 43575 0
6150 - Murdoch
Recruitment postcode(s) [3] 43577 0
3084 - Heidelberg
Recruitment postcode(s) [4] 43576 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 318145 0
Commercial sector/Industry
Name [1] 318145 0
3B Pharmaceuticals GmbH
Country [1] 318145 0
Germany
Primary sponsor type
Commercial sector/Industry
Name
3B Pharmaceuticals GmbH
Address
Country
Germany
Secondary sponsor category [1] 320529 0
Commercial sector/Industry
Name [1] 320529 0
Syneos Health Australia Pty Ltd
Address [1] 320529 0
Country [1] 320529 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317026 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 317026 0
Ethics committee country [1] 317026 0
Australia
Date submitted for ethics approval [1] 317026 0
17/01/2025
Approval date [1] 317026 0
14/03/2025
Ethics approval number [1] 317026 0
Ethics committee name [2] 316790 0
Bellberry Human Research Ethics Committee L
Ethics committee address [2] 316790 0
Ethics committee country [2] 316790 0
Australia
Date submitted for ethics approval [2] 316790 0
18/12/2024
Approval date [2] 316790 0
03/02/2025
Ethics approval number [2] 316790 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139022 0
Prof Andrew Scott
Address 139022 0
Austin Health; Level 1, Harold Stokes Building 145 Studley Road, 3084 Victoria
Country 139022 0
Australia
Phone 139022 0
+61 3 9496 5007
Fax 139022 0
Email 139022 0
[email protected]
Contact person for public queries
Name 139023 0
Kylie Wilkie
Address 139023 0
Olivia Newton-John Cancer Research Institute 145 Studley Road Heidelberg VIC 3084 Country Australia
Country 139023 0
Australia
Phone 139023 0
+61394963573
Fax 139023 0
Email 139023 0
[email protected]
Contact person for scientific queries
Name 139024 0
Kylie Wilkie
Address 139024 0
Olivia Newton-John Cancer Research Institute 145 Studley Road Heidelberg VIC 3084 Country Australia
Country 139024 0
Australia
Phone 139024 0
+61394963573
Fax 139024 0
Email 139024 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.