A study to investigate safety and anti-tumour activity of a Fibroblast Activation Protein (FAP)-targeting radiotracer (177Lu-FO-004) & Safety and Tolerability of a FAP imaging agent (68Ga-3BP-3940) in patients with advanced cancer.

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.