A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

Study Overview
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Brief Summary
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This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of [225Ac]-FPI-2068, [111In]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC).

Detailed Description
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The study will be conducted in 2 parts: Part A: optimization of the FPI-2053 dose (treatment with dose level 1 of [225Ac]-FPI-2068 - fixed dose). Part B: dose escalation of [225Ac]-FPI-2068 with optimal FPI-2053. Part B will commence once the optimal dose of FPI-2053 is determined in Part A. The RP2D will be determined from Part B based on all available safety, efficacy, PK, and dosimetry information.

Official Title
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A Phase 1, First-in-human, Multicentre, Open-label, Dose Escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

Conditions
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Advanced Solid Tumor, Metastatic Colorectal Carcinoma, Head and Neck Squamous Cell Carcinoma, Non-small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: FPI-2053
* Drug: [111In]-FPI-2107
* Drug: [225Ac]-FPI-2068


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically and/or cytologically confirmed solid tumor that is metastatic, locally advanced, recurrent or inoperable. Disease that has progressed despite prior treatment, and for which additional effective standard therapy is not available or is contraindicated, not tolerable, or the participant refuses standard therapy. Measurable disease as defined by RECIST Version 1.1 ECOG Performance status of 0 or 1 Adequate organ function Key Exclusion Criteria: Previous treatment with any systemic radiopharmaceutical Prior anti-cancer therapy unless adequate washout and recovery from toxicities Contraindications to or inability to perform the imaging procedures required in this study Radiation therapy (RT) within 28 days prior to the first dose of [111In]-FPI-2107 Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (≥ once per month) Patients with known CNS metastatic disease unless treated and stable

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Exploration and Dose Escalation<br>The study conducted in two parts: Part A Dose Exploration and Part B Dose Escalation FPI-2053 dose exploration to determine the optimal pre-dose administration of FPI-2053 with a fixed dose of [225Ac]-FPI-2068. [225Ac]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A. | Drug: FPI-2053<br>* FPI-2053 is a bispecific antibody that targets EGFR and cMET<br>Drug: [111In]-FPI-2107<br>* [111In]-FPI-2107 is an imaging agent in which indium-111 is conjugated to FPI-2053. Participants will have a fixed dose of [111In]-FPI-2107 followed by imaging scans (with or without pre-administration of FPI-2053).<br>Drug: [225Ac]-FPI-2068<br>* [225Ac]-FPI-2068 is a radiopharmaceutical therapy in which an alpha emitter, actinium-225, is conjugated to FPI-2053. Participants will be dosed through IV administration every 56 days for up to 3 cycles of the Treatment Period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068 | • Incidence of Adverse Events and evaluation of dosimetry | Approximately 4 years post final administration | 
| Radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest. | For Part A, evaluate the impact of pre-dose administration of FPI-2053 on the radiation dosimetry of [111In]-FPI-2107 (whole body, organs, and selected regions of interest) Estimate the effect of pre-dose administration of FPI-2053 on the radiation dosimetry of [225Ac]-FPI-2068 (whole body, organs, and selected regions of interest) | Within 56 days of administration | 
| Maximum tolerated dose of [225Ac]-FPI-2068 and FPI-2053 | Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053 | 56 days post administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess preliminary anti-tumor activity of [225Ac]-FPI-2068 | • Tumour assessments will be based on RECIST v1.1 (Eisenhauer et al, 2009) and will be performed approximately every 8 weeks (± 1 week) after the first [225Ac]-FPI-2068 dose, or as clinically indicated. | Approximately 4 years post final administration | 
| Tumor uptake of [111In]-FPI-2107 | • Tumor uptake of [111In]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images | Approximately 56 days of final administration | 
| Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life. | • Determine the plasma concentrations and PK parameters of [111In]-FPI-2107, and [225Ac]-FPI-2068 and the effect of pre-dose administration of FPI-2053 on the plasma concentrations and PK parameters of [111In]-FPI-2107. | Approximately 56 days of final administration | 
| To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053 | • Presence of ADA for [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053 | Approximately 56 days of final administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TAT, bsAb, FPI-2068, FPI-2107, FPI-2053, FPI-1784, Actinium-225, 225Ac, Indium-111, 111In, Solid tumors, Targeted alpha therapy, Epidermal growth factor receptor, EGFR, Mesenchymal-epithelial transition factor, cMET, Bispecific antibody, Radioimmuno-SPECT agent, Radioimmuno-therapeutic agent, Monoclonal antibody, Bifunctional chelating agent, Radiopharmaceutical therapy, Alpha particle emitter, Directed bispecific monovalent antibody, Bifunctional chelate, mCRC, HNSCC, NSCLC, PDAC, RLT, Radioligand Therapy, EGFRm, EGFRwt