A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours

NCT05363605 | Terminated Phase 1 FDA Drug

• 1 other identifier: FPI-1966-101
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 6

Brief Summary

This first-in-human study evaluates safety, tolerability and distribution of \[225Ac\] FPI-1966, \[111In\]-FPI-1967, and vofatamab in patients with FGFR3-expressing solid tumors.

Conditions

Advanced Solid Tumor; Head and Neck Squamous Cell Carcinoma; Bladder Carcinoma; Susceptible FGFR3 Genetic Alterations; FGFR3; FGFR3 Overexpression; FGFR3 Receptor; FGFR3 Protein Overexpression; Ovarian Cancer; Colorectal Cancer; Breast Cancer; Liver Cancer; Lung Cancer; Gastric Cancer

Keywords

Actinium-225; Targeted Alpha Therapy; Radiopharmaceutical; Radioimmunoconjugate; Theranostic; Theragnostic; Radioligand; Antineoplastic agents; [225Ac]-FPI-1966

Outcome Measures

Primary Outcomes (5)

• Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.

  Approximately 2 years post final administration

• Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966

  Approximately 42 days post administration.

• Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)

  Within one week of administration

• Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.

  Within one week of administration

• Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  Up to two years post final administration.

Secondary Outcomes (11)

• Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1

  Approximately 2 years post final administration

• Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images

  Within one week of administration

• Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)

  Within one week of administration

• Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.

  28 days post final [225Ac]-FPI-1966administration

• Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody

  28 days post final [225Ac]-FPI-1966administration.

Study Arms (2)

Phase 1

EXPERIMENTAL

Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered with or without pre-dosing with vofatamab.

Drug: [225Ac]-FPI-1966; Drug: [111In]-FPI-1967; Biological: vofatamab

Phase 2

EXPERIMENTAL

Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.

Drug: [225Ac]-FPI-1966; Drug: [111In]-FPI-1967; Biological: vofatamab

Interventions

[225Ac]-FPI-1966 DRUG

\[225Ac\]-FPI-1966 is a targeted alpha therapeutic that consists of vofatamab, a bifunctional chelate, and actinium-225, an alpha particle emitting radionuclide. In Phase 1, the dose depends on cohort assignment. In Phase 2, the RP2D regimen will be administered.

Phase 1; Phase 2

[111In]-FPI-1967 DRUG

\[111In\]-FPI-1967 is an imaging agent that consists of vofatamab, a bifunctional chelate and indium-111 radionuclide. Participants will receive \[111In\]-FPI-1967 Injection of 185 MBq for imaging.

Phase 1; Phase 2

vofatamab BIOLOGICAL

Vofatamab is a Fibroblast Growth Factor Receptor 3 (FGFR3)-targeting human monoclonal antibody without a radioisotope. In Phase 1, the dose depends on cohort assignment. In Phase 2, if pre-dosing with vofatamab is indicated, the RP2D regimen will be administered.

Phase 1; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed ICF prior to initiation of any study-specific procedures
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically and/or cytologically documented diagnosis of locally advanced, inoperable, or metastatic solid tumours
• Refractory to all standard treatments, or for whom standard treatment is not available, or tolerable, or is contraindicated, or the participant refuses standard therapy
• Measurable disease per RECIST v. 1.1
• Available tumour tissue (archival or fresh biopsy)
• Adequate bone marrow, heart, liver, and kidney function

You may not qualify if:

• Prior systemic radiopharmaceutical therapy within six months prior to the first dose of \[111In\]-FPI-1967
• Prior radiation therapy (RT) to bone marrow \> 20 Gy
• RT within 30 days prior to the first dose of \[111In\]-FPI-1967
• Prior anti-cancer treatment (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents) within a certain amount of time prior to administration of the first dose of \[111In\]-FPI-1967
• Concurrent serious co-morbidities that could limit participants' full participation and compliance

Sponsors & Collaborators

• Fusion Pharmaceuticals Inc.: lead

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

GC Murdoch

Murdoch, Western Australia, 6150, Australia

Location

St Vincent's Hospital

Melbourne, Australia

Location

Related Links

• Sponsor website

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Urinary Bladder Neoplasms; Ovarian Neoplasms; Colorectal Neoplasms; Breast Neoplasms; Liver Neoplasms; Lung Neoplasms; Stomach Neoplasms

Interventions

vofatamab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Liver Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Stomach Diseases

Study Officials

• Julia Kazakin, MD

  Fusion Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 6, 2022
• Study Start: April 20, 2022
• Primary Completion: September 8, 2023
• Study Completion: September 8, 2023
• Last Updated: December 19, 2023

Record last verified: 2023-12

Locations

US (4); AU (2)