A Phase 1/2 Study of [225Ac]-FPI-1434 Injection

Official Title

A Phase 1/2 Study of [225Ac]-FPI-1434 Injection in Patients With Locally Advanced or Metastatic Solid Tumours

Summary:

This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical trial designed to investigate safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumour activity of [111In]-FPI-1547 Injection (radioimmuno-imaging agent) and [225Ac]-FPI-1434 Injection (radioimmuno-therapeutic) and to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of repeat doses of [225Ac]-FPI-1434 Injection in patients with solid tumours that demonstrate uptake of [111In]-FPI-1547. The study consists of a Phase 1 portion that includes dose ascending cohorts (single and multi-dosing administration with/without cold antibody), a Cold Antibody Sub-Study, and a Phase 2 portion that includes tumour-specific cohorts.

Trial Description

Primary Outcome:

• Dose Escalation: Incidence of adverse events (AEs).
• Single-Dose Escalation: Incidence of dose limiting toxicities (DLTs).
• Multi-Dose Escalation: Incidence of DLTs.
• Dose Escalation: Incidence of clinically significant clinical laboratory abnormalities.
• Dose Escalation: Changes in electrocardiogram (ECG) parameters (PR, QRS, QT, and QTc intervals).
• Cold Antibody Sub-Study: Changes in uptake of [111In]-FPI-1547 Injection following FPI-1175 Infusion in selected regions of interest on SPECT/CT images.
• Cold Antibody Sub-Study: Changes in radiation dose estimates for selected tissues, organs and whole body both for [111In]-FPI-1547 and [225Ac]-FPI-1434 Injection at various dose levels following FPI-1175 Infusion.
• Evaluate anti-tumour activity of [225Ac]-FPI-1434 regimen

• Dose Escalation and Cold Antibody Sub-Study: Tumour uptake of [111In]-FPI-1547 in selected regions of interest on SPECT/CT images.
• Dose Escalation: Radiation doses for selected organs and whole body both for [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
• Dose Escalation and Cold-Antibody Sub-Study: Changes in radiation absorbed doses for tumour lesions for [225Ac]-FPI-1434.
• Dose Escalation and Cold-Antibody Sub-Study: Clearance for radioactivity and for the targeting antibody.
• Dose Escalation and Cold-Antibody Sub-Study: Area under the curve (AUC) for radioactivity and for the targeting antibody.
• Dose Escalation and Cold-Antibody Sub-Study: Cmax for radioactivity and for the targeting antibody.
• Dose Escalation and Cold-Antibody Sub-Study: Half-life for radioactivity and for the targeting antibody.
• Dose Escalation and Cold-Antibody Sub-Study: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 or Prostate Cancer Working Group 3 (PCWG3) guidelines.
• Dose Escalation: Changes in the corrected QT (QTc) interval in milliseconds after [225Ac]-FPI-1434 treatment, compared to baseline.
• Dose Escalation and Cold-Antibody Sub-Study: Changes in human growth hormone (hGh) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
• Dose Escalation and Cold-Antibody Sub-Study: Changes in insulin-like growth factor 1 (IGF-1) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
• Dose Escalation and Cold-Antibody Sub-Study: Changes in insulin-like growth factor binding protein 3 (IGFBP-3) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
• Cold Antibody Sub-Study: Incidence of AEs.
• Cold Antibody Sub-Study: Incidence of clinically significant clinical laboratory abnormalities.
• Cold Antibody Sub-Study: Changes in ECG parameters (PR, QRS, QT, and QTc intervals).
• Dose Escalation and Cold-Antibody Sub-Study: Time to response (TTR).
• Dose Escalation and Cold-Antibody Sub-Study: Duration of response (DoR).
• Dose Escalation and Cold-Antibody Sub-Study: Progression free survival (PFS).
• Dose Escalation and Cold-Antibody Sub-Study: Time to Progression (TTP).
• Dose Escalation and Cold-Antibody Sub-Study: Disease control rate (DCR).
• Dose Escalation and Cold-Antibody Sub-Study: Overall survival (OS).

View this trial on ClinicalTrials.gov