2158 - A First-in-Human Study of the Radiopharmaceutical [²²⁵Ac]-FPI-2068 in Patients (pts) with Advanced Solid Tumors

G. A. Ulaner¹, A. Juloori², T. Burns³, D. Juneau⁴, A. H. Iagaru⁵, J. Schindler⁶, S. Allan⁷, L. Jean-Louis⁸, G. J. Lunger⁷, M. Nawine⁹, N. Mueller⁹, G. Littlewood⁹, and W. Trigg⁹; ¹University of Southern California, Los Angeles, CA, ²Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, ³UPMC Hillman Cancer Center, Pittsburgh, PA, ⁴Département de médecine nucléaire, Centre Hospitalier de lUniversité de Montréal (CHUM), Montréal, QC, Canada, ⁵Stanford University, Palo Alto, CA, ⁶Fusion Pharmaceuticals, Bostong, MA, ⁷Fusion Pharmaceuticals, Boston, MA, ⁸Fusion Pharmaceutcals, Boston, MA, ⁹AstraZeneca, Cambridge, United Kingdom

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

Methods: This is a phase 1, non-randomized, multicenter, open-label clinical study. Pts with advanced, metastatic and/or recurrent solid tumors (NSCLC, PDAC, CRC and HNSCC) that demonstrate uptake of the imaging agent as determined by SPECT/CT will be evaluated. Up to 110 pts 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 FPI-2068.
• Part B: 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 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. Pts will be dosed through intravenous administration every 56 days. Treatment can continue for 3 cycles of 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 FPI-2068 and FPI-2107, to determine the appropriate dose and the effect of pre-dose administration of FPI-2053 on the safety, tolerability and biodistribution of FPI-2068 and FPI-2107, and to determine the recommended Phase 2 Dose of FPI-2068 given with or without FPI-2053. The secondary objectives are to assess the pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of FPI-2068 regimen. The study will include sites in the USA and Canada.
Results: TBD
Conclusion: TBD Clinical Trial Identifier is NCT06147037.