Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT) (TANGENT)

A Phase III, Multicentre, Randomised, Double-Blind Study to Assess the Safety and Efficacy of Emactuzumab vs. Placebo in Subjects With Tenosynovial Giant Cell Tumour

This is a multicenter, Phase 3, randomised, double-blind, placebo-controlled study, which aims to evaluate the efficacy and safety of the investigational drug emactuzumab for the treatment of patients with localized or diffuse TGCT where surgical removal of the tumor is not viewed as an option.

The study consists of two parts. In Part 1, eligible subjects will be assigned in a 2:1 ratio to receive either emactuzumab or matching placebo in a double-blind fashion, that will be administered in total 5 times as an intravenous (i.v.) infusion once every 2 weeks. This will be followed by an observation period of 3 months leading to a total duration of 24 weeks in Part 1. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. Part 2 is a long-term double-blind follow-up phase of the subjects on emactuzumab or placebo. Subjects assigned to placebo in Part 1 have the option, subject to eligibility, to crossover to receive open-label emactuzumab in Part 2. Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment under certain circumstances.

Study Overview

• Status: Active, not recruiting
• Conditions: TGCT
• Intervention / Treatment: Drug: Emactuzumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LKH-Universitätsklinikum Graz
• Belgium
  • Ghent, Belgium, 9000
    • UZ Gent - Department of Medical Oncology
  • Brussels Capital
    • Woluwe-Saint-Lambert, Brussels Capital, Belgium, 1200
      • Cliniques Universitaires Saint-luc
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Arthur J.E. Child Comprehensive Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • McGill University Health Centre (MUHC)
• France
  • Lille, France, 59000
    • UNICANCER - Centre Oscar Lambret
  • Paris, France, 75248
    • Institut Curie - Hôpital de Paris
  • Toulouse, France, 31059
    • Oncopole Claudius Regaud Oncologie Médicale
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06189
      • Centre Antoine Lacassagne
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Institut Bergonie - PPDS
  • Loire-Atlantique
    • Saint-Herblain, Loire-Atlantique, France, 44115
      • Institut de Cancerologie de Ouest - Saint Herblain
  • Paris
    • Paris, Paris, France, 75014
      • AP-HP - Hôpital Cochin - Port-Royal, site Cochin
  • Rhône
    • Lyon, Rhône, France, 69373
      • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
• Italy
  • Bologna, Italy, 40136
    • IRCCS lstituto Ortopedico Rizzoli
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Pisa, Italy, 56124
    • Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
  • Lazio
    • Rome, Lazio, Italy, 00128
      • Fondazione Policlinico Universitario Campus Bio-Medico
  • Piedmont
    • Candiolo, Piedmont, Italy, 10060
      • Fondazione del Piemonte per l'Oncologia (IRCCS)
  • Sicily
    • Palermo, Sicily, Italy, 90127
      • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • Tuscany
    • Pisa, Tuscany, Italy, 56126
      • Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
    • Prato, Tuscany, Italy, 59100
      • Nuovo Ospedale di Prato
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum
• South Korea
  • Seoul, South Korea, 3080
    • Seoul National University Hospital
• Spain
  • Barcelona, Spain, 8041
    • Hospital de la Santa Creu i Sant Pau
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio - PPDS
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Madrin
    • Madrid, Madrin, Spain, 28040
      • Hospital Clinico San Carlos
  • Zaragoza
    • Zaragoza, Zaragoza, Spain, 50009
      • Hospital Universitario Fundacion Jimenez Diaz
• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 222 42
      • Skånes Universitetssjukhus Lund
• Switzerland
  • Basel, Switzerland, 4031
    • Universitäts Kinderspital Beider Basel (UKBB)
  • Bern, Switzerland, 3010
    • Inselspital - Universitätsspital Bern
• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital
  • London, United Kingdom, NW1 2BU
    • University College Hospital
  • Oxford, United Kingdom, OX3 7LD
    • Churchill Hospital, Cancer Haematology Center
• United States
  • California
    • Beverly Hills, California, United States, 90212
      • NextGen Oncology
    • Los Angeles, California, United States, 90089
      • USC Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90067
      • Sarcoma Oncology Research Center, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center (Overland Park) - USOR
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43201
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute Hematology Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Georgetown, Washington, United States, 20010
      • Medstar Washington Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >12 years
• Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where surgical resection would be associated with predicted worsening functional limitations through surgical joint damage, and/or subject has an anticipated high risk of early recurrence as determined by a multidisciplinary tumour board or equivalent, or any other morbidity associated with the surgery, and/or surgical treatment is not expected to improve the clinical outcomes of the subject.
• Measurable disease: longest diameter ≥20 mm.
• Adequate organ and bone marrow function
• If a woman of childbearing potential (WOCBP), must have a negative pregnancy test prior to starting treatment and agree to use a highly effective method of contraception
• Participants must have given written consent

Exclusion Criteria:

• If a female, the subject is pregnant or breast feeding.
• Medical conditions, including auto-immune, requiring systemic immunosuppression. Any systemic treatment for these conditions (eg, glucocorticoids) is not allowed within 4 weeks of Screening and during the study.
• Known metastatic TGCT or other active cancer that requires concurrent or planned treatment
• Received systemic therapy for TGCT (investigational or approved) targeting CSF-1 or CSF-1R or any multi-tyrosine kinase inhibitor (eg nilotinib and imatinib) within 3 months prior to screening
• Any surgery, chemotherapy or radiotherapy within 3 months of screening
• Unresolved clinically significant toxicity from a previous treatment or any history of serious liver toxicity.
• Current or chronic history of liver disease.
• Inadequate renal and liver function
• Systemic antiretroviral therapy within 3 months of baseline
• Within 6 months of baseline has experienced: clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994) including severe thromboembolic event; incompletely healed clinically significant wounds, including bone fractures; pathological fracture or significant hypercalcaemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 in Part 1/Part 2: Emactuzumab; Group 1: Subjects receiving emactuzumab administered intravenously (i.v) on Day(D)1 and repeated once every two weeks (Q2W) for a total of 5 times, followed by an observation period of 3 months leading to a total period of 24 weeks in Part 1 and continued with a follow-up phase in Part 2. Eligible Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment in Part 2.	Drug: Emactuzumab; Emactuzumab administered once every 2 weeks (q2w)
Placebo Comparator: Group 2 in Part 1 and Part 2: Placebo; Group 2: Subjects receiving placebo administered intravenously (i.v) on D1 and repeated once every two weeks (Q2W) for 5 times followed by an observation period of 3 months to a total period of 24 weeks in Part 1. In Part 2, Eligible Subjects will have the option to receive open-label emactuzumab, administered by i.v once every 2 weeks (Q2W) for a total of 5 times.	Drug: Placebo; Matching placebo administered once every 2 weeks (q2w)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Objective Response Rate (ORR = complete response [CR] + partial response [PR]) by 6 months from initiation of therapy according to RECIST v1.1 based on independent, blinded central review	Day 0 - Day 180 (6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Function	Change in Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) TGCT from baseline to 6 months	up to 24 months
Range of Motion (ROM)	Mean change from baseline in active ROM of the joint over time	up to 24 months
Worst Stiffness	Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score over time	up to 24 months
Worst Pain	Mean change in Pain Numerical Rating Scale (NRS) from baseline over time	up to 24 months
Quality of Life (QoL)	Change in EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L)	up to 24 months
Duration of response (DoR)	Duration of response (DoR) as measured by RECIST version 1.1	up to 24 months
Tumour volume score (TVS)	Change in Tumour volume score (TVS)	up to 24 months
Surgical Intervention Rate	The number of subjects who undergo surgery during the study for TGCT	up to 24 months

Collaborators and Investigators

• Sponsor: SynOx Therapeutics Limited
• Investigators: Principal Investigator: Jean Y Blay, Prof, MD, Comprehensive Cancer Centre of Lyon

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2024
• Primary Completion (Actual): December 23, 2025
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Synovitis; TGCT, Tenosynovial Giant Cell Tumour; PVNS, Pigmented Villonodular Synovitis; Emactuzumab; Local TGCT; Diffuse TGCT
• Additional Relevant MeSH Terms: Giant Cell Tumor of Tendon Sheath; Musculoskeletal Diseases; Muscular Diseases; Neoplasms; Joint Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Tendinopathy; Giant Cell Tumors; Synovitis; Synovitis, Pigmented Villonodular; emactuzumab
• Other Study ID Numbers: SNX-301-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Summary (synopsis) of the CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No