Clinical trial NCT06147037: A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Colorectal Carcinoma
Head and Neck Squamous Cell Carcinoma
Non-small Cell Lung Cancer
Pancreatic Ductal Adenocarcinoma
Keywords: FPI-2068
FPI-2107
FPI-2053
FPI-1784
Actinium-225
225Ac
Indium-111
111In
Solid tumors
Targeted alpha therapy
TAT
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
bsAb
Bifunctional chelate
mCRC
HNSCC
NSCLC
PDAC
RLT
Radioligand Therapy
EGFRm
EGFRwt
Lead sponsor: Fusion Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2023-11-27
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
timeFrame: Approximately 4 years post final administration
measure: Radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.
timeFrame: Within 56 days of administration
measure: Maximum tolerated dose of [225Ac]-FPI-2068 and FPI-2053
timeFrame: 56 days post administration
Secondary outcomes:
measure: Assess preliminary anti-tumor activity of [225Ac]-FPI-2068
timeFrame: Approximately 4 years post final administration
measure: Tumor uptake of [111In]-FPI-2107
timeFrame: Approximately 56 days of final administration
measure: Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life.
timeFrame: Approximately 56 days of final administration
measure: To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053
timeFrame: Approximately 56 days of final administration
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Hoag Hospital
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center Research Pavilion
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington/Fred Hutchinson Cancer Center
state: Washington
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre| Nova Scotia Health Authority
state: Nova Scotia
city: Montréal
country: Canada
facility: CHUM
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - CHUS
state: Quebec
Study officials:
affiliation: Fusion Pharmaceuticals Inc.
name: Lorraine Hughes, MS
role: STUDY_DIRECTOR
References: