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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06147037
• Other study ID #: FPI-2068-101
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 28, 2024
• Est. completion date: December 30, 2027

Study information

• Verified date: May 2024
• Source: Fusion Pharmaceuticals Inc.
• Contact: Clinical Trials Fusion Pharmaceuticals Clinical Operations
• Phone: 1 (888) 506-4215
• Email: clinicaltrials[@]fusionpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 110
• Est. completion date: December 30, 2027
• Est. primary completion date: December 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma
• Colorectal Neoplasms
• Head and Neck Squamous Cell Carcinoma
• Metastatic Colorectal Carcinoma
• Non-small Cell Lung Cancer
• Pancreatic Ductal Adenocarcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• FPI-2053
FPI-2053 is a bispecific antibody that targets EGFR and cMET
• [111In]-FPI-2107
[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).
• [225Ac]-FPI-2068
[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.

Locations

Country	Name	City	State
Canada	CHUM	Montréal	Quebec
Canada	CIUSSS de l'Estrie - CHUS	Sherbrooke	Quebec
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Hoag Hospital	Irvine	California
United States	UPMC Hillman Cancer Center Research Pavilion	Pittsburgh	Pennsylvania
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Washington/Fred Hutchinson Cancer Center	Seattle	Washington
United States	Stanford Hospital and Clinics	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Fusion Pharmaceuticals Inc.	AstraZeneca

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Sponsor Website