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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor; Non-small Cell Lung Cancer; Metastatic Colorectal Carcinoma; Head and Neck Squamous Cell Carcinoma; Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: FPI-2053; Drug: [111In]-FPI-2107; Drug: [225Ac]-FPI-2068

• Registration Number: NCT06147037
• Lead Sponsor: Fusion Pharmaceuticals Inc.

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2023-11-20
• Study First Submitted QC: 2023-11-20
• Study First Posted: 2023-11-27
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-28
• Last Update Posted: 2024-07-01
• Study Start: 2024-07-31
• Primary Completion: 2026-12-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Exploration and Dose Escalation	[225Ac]-FPI-2068	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.
Dose Exploration and Dose Escalation	[111In]-FPI-2107	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.
Dose Exploration and Dose Escalation	FPI-2053	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.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of [225Ac]-FPI-2068 and FPI-2053	56 days post administration	Determine the RP2D of \[225Ac\]-FPI-2068, given with or without FPI-2053
Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068	Approximately 4 years post final administration	• Incidence of Adverse Events and evaluation of dosimetry
Radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.	Within 56 days of administration	* 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)

Secondary Outcome Measures

Name	Time	Method
Assess preliminary anti-tumor activity of [225Ac]-FPI-2068	Approximately 4 years post final administration	• 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.
Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life.	Approximately 56 days of final administration	• 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.
Tumor uptake of [111In]-FPI-2107	Approximately 56 days of final administration	• Tumor uptake of \[111In\]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images
To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053	Approximately 56 days of final administration	• Presence of ADA for \[111In\]-FPI-2107, \[225Ac\]-FPI-2068, and FPI-2053

Trial Locations

Locations (11)

Hoag Hospital; 🇺🇸 Irvine, California, United States

Stanford Hospital and Clinics; 🇺🇸 Stanford, California, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Washington University in St. Louis; 🇺🇸 St. Louis, Missouri, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

UPMC Hillman Cancer Center Research Pavilion; 🇺🇸 Pittsburg, Pennsylvania, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Washington/Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

CHUM; 🇨🇦 Montréal, Quebec, Canada

CIUSSS de l'Estrie - CHUS; 🇨🇦 Sherbrooke, Quebec, Canada