Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)

NCT05417789 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: SNX-301-020
• Study Type: interventional
• Target: 128
• Locations: 13 countries
• Sites: 48

Brief Summary

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.

Conditions

TGCT

Keywords

TGCT, Tenosynovial Giant Cell Tumour; PVNS, Pigmented Villonodular Synovitis; Synovitis; Emactuzumab; Local TGCT; Diffuse TGCT

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Physical Function

  up to 24 months

• Range of Motion (ROM)

  up to 24 months

• Worst Stiffness

  up to 24 months

• Worst Pain

  up to 24 months

• Quality of Life (QoL)

  up to 24 months

Study Arms (2)

Group 1 in Part 1/Part 2: Emactuzumab

EXPERIMENTAL

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

Group 2 in Part 1 and Part 2: Placebo

PLACEBO COMPARATOR

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

Interventions

Emactuzumab DRUG

Emactuzumab administered once every 2 weeks (q2w)

Group 1 in Part 1/Part 2: Emactuzumab

Placebo DRUG

Matching placebo administered once every 2 weeks (q2w)

Group 2 in Part 1 and Part 2: Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• SynOx Therapeutics Limited: lead

Study Sites (48)

NextGen Oncology

Beverly Hills, California, 90212, United States

Location

Sarcoma Oncology Research Center, LLC

Los Angeles, California, 90067, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90089, United States

Location

University of Kansas Cancer Center (Overland Park) - USOR

Overland Park, Kansas, 66210, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University

Columbus, Ohio, 43201, United States

Location

OHSU Knight Cancer Institute Hematology Oncology

Portland, Oregon, 97239, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MedStar Washington Hospital Center

Georgetown, Washington, 20010, United States

Location

LKH-Universitätsklinikum Graz

Graz, 8036, Austria

Location

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

UZ Gent - Department of Medical Oncology

Ghent, 9000, Belgium

Location

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 4N1, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University Health Centre (MUHC)

Montreal, Quebec, H1T 2M4, Canada

Location

Centre Antoine Lacassagne

Nice, Alpes-Maritimes, 06189, France

Location

Institut Bergonie - PPDS

Bordeaux, Gironde, 33000, France

Location

Institut de Cancerologie de Ouest - Saint Herblain

Saint-Herblain, Loire-Atlantique, 44115, France

Location

AP-HP - Hôpital Cochin - Port-Royal, site Cochin

Paris, Paris, 75014, France

Location

Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes

Lyon, Rhône, 69373, France

Location

UNICANCER - Centre Oscar Lambret

Lille, 59000, France

Location

Institut Curie - Hôpital de Paris

Paris, 75248, France

Location

Oncopole Claudius Regaud Oncologie Médicale

Toulouse, 31059, France

Location

Fondazione Policlinico Universitario Campus Bio-Medico

Rome, Lazio, 00128, Italy

Location

Fondazione del Piemonte per l'Oncologia (IRCCS)

Candiolo, Piedmont, 10060, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Sicily, 90127, Italy

Location

Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello

Pisa, Tuscany, 56126, Italy

Location

Nuovo Ospedale di Prato

Prato, Tuscany, 59100, Italy

Location

IRCCS lstituto Ortopedico Rizzoli

Bologna, 40136, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello

Pisa, 56124, Italy

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Hospital Clinico San Carlos

Madrid, Madrin, 28040, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Zaragoza, Zaragoza, 50009, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 8041, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Skanes Universitetssjukhus Lund

Lund, Skåne County, 222 42, Sweden

Location

Universitäts Kinderspital Beider Basel (UKBB)

Basel, 4031, Switzerland

Location

Inselspital - Universitätsspital Bern

Bern, 3010, Switzerland

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

Churchill Hospital, Cancer Haematology Center

Oxford, OX3 7LD, United Kingdom

Location

MeSH Terms

Conditions

Synovitis, Pigmented Villonodular; Synovitis

Interventions

emactuzumab

Condition Hierarchy (Ancestors)

Giant Cell Tumor of Tendon Sheath; Giant Cell Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Tendinopathy; Muscular Diseases

Study Officials

• Jean Y Blay, Prof, MD

  Comprehensive Cancer Centre of Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 14, 2022
• Study Start: October 9, 2024
• Primary Completion: December 23, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); BE (2); TW (2); ES (6); NL (1); KR (1); GB (3); AU (1); IT (8); SE (1); FR (8); CA (3); CH (2)