A Phase 1, First-in-human, Multicentre, Open-label, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients with Advanced Solid Tumors

Introduction: Background: The epidermal growth factor receptor (EGFR) and mesenchymal-epidermal transition tyrosine kinase receptor (c-MET) are frequently upregulated and co-expressed in diverse solid tumors including non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), metastatic colorectal cancer (mCRC), and head and neck squamous cell carcinoma (HNSCC). [²²⁵Ac]-FPI-2068 is an EGFR/c-MET targeting bispecific antibody (FPI-2053) linked to the alpha emitting radioisotope actinium-225 which has been shown to have promising efficacy in a range of preclinical tumor models. [¹¹¹In]-FPI-2107 is the corresponding imaging theranostic partner (indium-111 conjugated to FPI-2053) that can be used to assess eligibility for treatment with [²²⁵Ac]-FPI-2068 and to enable estimation of tumor and normal organ dosimetry for [²²⁵Ac]-FPI-2068.

Methods: FPI-2068-101 is a first-in-human, phase 1, non-randomized, multicentre, open-label clinical study.

Up to 110 patients will be enrolled in the study, which will be conducted in 2 parts:

• Part A: FPI-2053 dose exploration to determine the optimal predose administration of FPI-2053 with treatment at dose level 1 of [²²⁵Ac]-FPI-2068.

• Part B: [²²⁵Ac]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A.

Key inclusion criteria are age ≥18 years, ECOG performance status 0–1, measurable disease per RECIST v1.1, adequate organ and bone marrow function, tumor to background ratio ≥2 in at least 1 extrahepatic lesion and life expectancy of ≥3 months.

Key exclusion criteria include unresolved toxicities from prior therapy, prior treatment with any systemic radiopharmaceutical, radiation therapy within 28 days of the first [¹¹¹In]-FPI-2107 dose, uncontrolled pleural effusion, uncontrolled pericardial effusion, ascites requiring recurrent drainage procedures (≥ once per month) and known CNS metastatic disease, unless treated and stable.

Patients will be dosed through intravenous administration every 56 days. Treatment can continue for 3 cycles of [²²⁵Ac]-FPI-2068 or until disease progression, initiation of alternative anticancer therapy or unacceptable toxicity.

The primary objectives of the study are to investigate the safety, tolerability, dosimetry and biodistribution of [²²⁵Ac]-FPI-2068 and [¹¹¹In]-FPI-2107, to determine the appropriate dose and the effect of pre-dose administration of FPI-2053 on the safety, tolerability and biodistribution of [²²⁵Ac]-FPI-2068 and [¹¹¹In]-FPI-2107, and to determine the recommended Phase 2 Dose (RP2D) of [²²⁵Ac]-FPI-2068 given with or without FPI-2053. The secondary objectives are to assess the pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of [²²⁵Ac]-FPI-2068 regimen. Participants with advanced, metastatic and/or recurrent solid tumors (NSCLC, PDAC, mCRC and HNSCC) that demonstrate uptake of the imaging agent as determined by SPECT/CT will be evaluated.

The study will include sites in the USA and Canada. Clinical Trial Identifier is NCT06147037.

Results: This is a Trial in Progress.

Conclusions: This is a Trial in Progress.