A Dose Escalation Study of Radio-labeled Antibody for the Treatment of Advanced Cancer

A Phase 1 Dose-escalation Study of Radio- Labeled Antibody, FF-21101(90Y) for the Treatment of Advanced Cancer

The purpose of this study is to determine the safety and tolerability in subjects who receive FF-21101(111In) for dosimetry and FF-21101(90Y) for treatment of advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Biological: FF21101

Detailed Description

The purpose of this study is to determine the safety and tolerability in subjects who receive FF-21101(111In) for dosimetry and FF-21101(90Y) for treatment of advanced solid tumors. This is an open label study that will recruit approx 70 patients

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute - Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University - Feinberg School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females ≥ 18 years of age
• Histologically or cytologically confirmed advanced solid tumor malignancy, refractory or relapsed from prior therapy, or for whom no alternative therapy is available
• At least 4 weeks beyond the last chemotherapy (or ≥ 5 half-lives for targeted agents, whichever is shorter), radiotherapy, major surgery or experimental treatment and recovered from all acute toxicities (≤ Grade 1)
• Archival tumor sample available, or be willing to undergo a fresh tumor biopsy, prior to study
• At least one measurable disease site that meets target lesion requirements
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Life expectancy of ≥ 3 months
• Adequate hematologic parameters without ongoing transfusional support:
• Negative serum pregnancy test
• Ability to provide written informed consent

Exclusion Criteria:

• Previous radioimmunotherapy. Previous antibody-based therapy is allowed as long as ≥ 28 days has elapsed from last dose to study treatment.
• Prior radiation to > 30% of the red marrow or to maximal tolerable level for any organ
• Serious cardiac condition within the last 6 months
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of antimicrobials that are considered to be essential for care of the patient
• History of retinal degenerative disease, history of uveitis, history of retinal vein occlusion (RVO), or any eye condition that would be considered a risk factor for RVO or has medically relevant abnormalities identified on screening ophthalmologic examination
• Active central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior, or currently treated brain metastases are allowed.
• Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
• Known autoimmune disease
• Active infection requiring intravenous (IV) antibiotic usage within the last week prior to the dosimetry portion of the study
• Corticosteroid use within 2 weeks of study treatment
• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence with study requirements or confound the interpretation of study results
• Pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lowest dose of FF-21101(90Y); In the therapeutic phase subjects in this cohort will receive one dose of radiolabeled FF21101	Biological: FF21101; (90Y) radio-labeled FF21101 (therapeutic monoclonal antibody to P-cadherin expressed by the CDH3 gene)
Experimental: 2X Lowest dose of FF-21101(90Y); In the therapeutic phase subjects in this cohort will receive one dose of radiolabeled FF21101 that is 2X the lowest dose	Biological: FF21101; (90Y) radio-labeled FF21101 (therapeutic monoclonal antibody to P-cadherin expressed by the CDH3 gene)
Experimental: 3X Lowest dose of FF-21101(90Y); In the therapeutic phase subjects in this cohort will receive one dose of radiolabeled FF21101 that is 3X the lowest dose	Biological: FF21101; (90Y) radio-labeled FF21101 (therapeutic monoclonal antibody to P-cadherin expressed by the CDH3 gene)
Experimental: 4X Lowest dose of FF-21101(90Y); In the therapeutic phase subjects in this cohort will receive one dose of radiolabeled FF21101 that is 4X the lowest dose	Biological: FF21101; (90Y) radio-labeled FF21101 (therapeutic monoclonal antibody to P-cadherin expressed by the CDH3 gene)
Experimental: 5X Lowest dose of FF-21101(90Y); In the therapeutic phase subjects in this cohort will receive one dose of radiolabeled FF21101 that is 5X the lowest dose	Biological: FF21101; (90Y) radio-labeled FF21101 (therapeutic monoclonal antibody to P-cadherin expressed by the CDH3 gene)
Experimental: Expansion Phase (Cohort 6), Ovarian; In the expansion phase, subjects in this cohort will be diagnosed with epithelial ovarian, peritoneal or fallopian tube carcinoma and will receive a dose of 25 mCi/m2 FF-21101(90Y)	Biological: FF21101; (90Y) radio-labeled FF21101 (therapeutic monoclonal antibody to P-cadherin expressed by the CDH3 gene)
Experimental: Expansion Phase (Cohort 7), Adv Tumors; In the expansion phase, subjects in this cohort will be diagnosed with triple negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), biliary cancer (cholangiocarcinoma or gall bladder carcinoma), pancreatic carcinoma, colorectal cancer and will receive a dose of 25 mCi/m2 FF-21101(90Y)	Biological: FF21101; (90Y) radio-labeled FF21101 (therapeutic monoclonal antibody to P-cadherin expressed by the CDH3 gene)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of radio-labeled FF21101	measured by number of patients with adverse events leading to discontinuation or number of patients with dose limiting toxicity	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients achieving overall response using Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1)	Overall response rates are defined as the number of patients achieving a best response of complete response [CR], partial response [PR], stable disease [SD], or progressive disease [PD])	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients expressing CDH3 (human cadherin 3/P-cadherin) as a predictor of clinical activity	measurement of CDH3 expression	Single sample taken at enrollment

Collaborators and Investigators

• Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: May 4, 2015
• First Submitted That Met QC Criteria: May 21, 2015
• First Posted (Estimate): May 27, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: FF21101US101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No