emactuzumab (RG7155) / Roche, SynOx Therap - LARVOL DELTA

SynOx Therapeutics Completes Enrollment in Registrational Phase 3 TANGENT Clinical Trial Significantly Ahead of Timeline (GlobeNewswire) - "SynOx Therapeutics Limited...announced completion of patient enrolment in the TANGENT study. TANGENT is the company’s global, multi-centre, randomized, double-blind, placebo-controlled registrational Phase 3 trial of emactuzumab in patients with TGCT who are not amenable to or who would not benefit from surgery. SynOx expects to report top-line data from the study in the first quarter of 2026."

Enrollment closed • P3 data: top line • Tenosynovial Giant Cell Tumor

A phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of emactuzumab in patients with tenosynovial giant cell tumor (TANGENT). (ASCO 2025) - P3 | "Assessments include tumor evaluation, physical examination, vital signs, electrocardiograms, questionnaires, urinalyses, and blood tests for hematology, biochemistry, and PK of emactuzumab. Safety will be assessed by laboratory assessments and evaluation of adverse events."

Clinical • P3 data • Giant Cell Tumor of Bone • Oncology • Pain • Tenosynovial Giant Cell Tumor

Medical Management of Tenosynovial Giant Cell Tumor. (PubMed, Curr Oncol Rep) - "For an alternative to surgery, the CSF1R inhibitors pexidartinib and vimseltinib are approved in the United States for TGCT, and other CSF1R inhibitors are in clinical development...The potential risks and benefits of available treatments should be carefully considered in collaboration with a bone tumor-experienced, multidisciplinary team to determine the best course of care. Increased D-TGCT awareness and support through patient advocacy groups have helped to reshape the patient journey."

Journal • Review • Giant Cell Tumor of Bone • Oncology • Osteosarcoma • Solid Tumor • Tenosynovial Giant Cell Tumor

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

SynOx Therapeutics Receives Fast Track Designation from U.S. Food and Drug Administration for Emactuzumab for Tenosynovial Giant Cell Tumours (TGCT) (GlobeNewswire) - "SynOx Therapeutics Limited...announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to emactuzumab for the treatment of TGCT patients that are not amenable to or who would not benefit from surgery. Emactuzumab, a potentially best-in-class CSF-1 receptor (CSF-1R) inhibiting monoclonal antibody, is currently being evaluated in the TANGENT study, a global, multi-centre, randomized, double-blind, placebo-controlled registrational Phase 3 trial."

Fast track • Tenosynovial Giant Cell Tumor

SynOx Therapeutics Announces Board Chair Transition to Align with Advancing Regulatory and Commercialization Strategy (GlobeNewswire) - "Strengthened Leadership and Expanded U.S. Presence Positions SynOx for Regulatory Filings and Commercialization of Emactuzumab for Tenosynovial Giant Cell Tumours (TGCT)."

Commercial • Tenosynovial Giant Cell Tumor

TANGENT: A phase III, global, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of emactuzumab in patients with tenosynovial giant cell tumor (Sarcoma-RC 2025) - P3 | "The Phase 3 study is enrolling patients. Trial Design Phase 3, global, double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of fixed i.v. infusions of emactuzumab in TGCT patients."

Clinical • P3 data • Giant Cell Tumor of Bone • Musculoskeletal Pain • Oncology • Pain • Tenosynovial Giant Cell Tumor

A PHASE 3 MULTI-CENTER, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO ASSESS THE EFFICACY AND SAFETY OF EMACTUZUMAB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR TANGENT) (CTOS 2024) - P3 | "There are currently no worldwide approved systemic therapies available for the treatment of patients with TGCT. Emactuzumab demonstrated a favorable risk-benefit profile in early phase clinical studies without the need of chronic and/or daily treatment, which has been recognized to be important for the future treatment of TGCT. The efficacy and safety of emactuzumab in patients with TGCT will be further assessed in the Phase 3 TANGENT trial.References:1."

Clinical • P3 data • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

SynOx Therapeutics Further Strengthens Executive Team with Appointments of U.S.-Based Chief Medical Officer and Chief Commercial Officer (GlobeNewswire) - "SynOx Therapeutics Limited...today announced the appointments of Elyse Seltzer, M.D., as Chief Medical Officer (CMO) and Robert Francomano as Chief Commercial Officer (CCO). These strategic hires come at a pivotal time as SynOx accelerates the clinical development of emactuzumab, a potentially best-in-class CSF-1R inhibiting monoclonal antibody...'SynOx expects that his experience will be vital in preparing for the potential commercialization of emactuzumab and expanding the company’s footprint in the global market.'"

Clinical • Tenosynovial Giant Cell Tumor

SynOx Therapeutics Adds New Investor and Capital to Series B Financing, Raising Total to $92 Million, and Doses First Patients in Phase 3 Trial (GlobeNewswire) - "SynOx Therapeutics Limited...announced that it has raised additional funding in a final close of its Series B financing....Proceeds from the financing are supporting a registrational Phase 3 clinical trial of emactuzumab, a potentially best-in-class CSF-1 receptor (CSF-1R) inhibiting monoclonal antibody for the treatment of Tenosynovial Giant Cell Tumour (TGCT). In conjunction with the closing of the Series B extension, SynOx today announced that the first patients have been dosed in its Phase 3 registrational study of emactuzumab."

Financing • Trial status • Tenosynovial Giant Cell Tumor

TANGENT: Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT) (clinicaltrials.gov) - P3 | N=128 | Recruiting | Sponsor: SynOx Therapeutics Limited | Trial primary completion date: Sep 2027 ➔ Apr 2026

Trial primary completion date • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

SynOx Therapeutics secures up to $35m debt financing with Hercules Capital to progress development and commercialisation of emactuzumab (PRNewswire) - "SynOx Therapeutics Limited...announces it has entered into a $35m loan facility with Hercules Capital....The transaction strengthens the Company's balance sheet as it executes TANGENT, a registrational Phase 3 study of emactuzumab, SynOx's potentially best-in-class CSF-1(R) inhibiting monoclonal antibody (mAb) for the treatment of TGCT. This loan facility provides SynOx with flexibility to fund additional clinical work in TGCT to augment TANGENT, activities to support the successful registration and commercialisation of emactuzumab in TGCT, and potentially to explore the use of emactuzumab in other CSF-1 driven and macrophage-mediated diseases."

Financing • Tenosynovial Giant Cell Tumor

SynOx Therapeutics announces $75m Series B round to fund Phase 3 trial of potential best-in-class treatment for TGCT (PRNewswire) - SynOx Therapeutics Limited...is pleased to announce the close of a $75m Series B financing....The proceeds will be used to generate registrational Phase 3 clinical and CMC data for emactuzumab, SynOx's potentially best-in-class CSF-1(R) inhibiting monoclonal antibody (mAb) for the treatment of Tenosynovial Giant Cell Tumour (TGCT)....SynOx is initiating a Phase 3 trial (TANGENT) to assess the efficacy and safety of emactuzumab in patients with localized and diffuse TGCT....'We are pleased to continue to support the SynOx team as it moves emactuzumab through to BLA and MAA submissions in TGCT.'"

Financing • Trial status • Tenosynovial Giant Cell Tumor

TANGENT: Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT) (clinicaltrials.gov) - P3 | N=128 | Not yet recruiting | Sponsor: SynOx Therapeutics Limited | Trial completion date: Sep 2025 ➔ Sep 2027 | Trial primary completion date: Dec 2023 ➔ Sep 2027

Trial completion date • Trial primary completion date • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

Paclitaxel and Bevacizumab With or Without Emactuzumab in Treating Patients With Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P2 | N=9 | Terminated | Sponsor: M.D. Anderson Cancer Center | Completed ➔ Terminated; The study was terminated early by the Sponsor

Trial termination • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

Updates on the Treatment of Tenosynovial Giant Cell Tumor. (PubMed, Hematol Oncol Stem Cell Ther) - "Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab."

Journal • Review • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

Malignant Tenosynovial Giant Cell Tumor May Harbor Mutation Other Than CSF1: A clinicopathologic study of 28 cases (USCAP 2023) - "While the majority of diffuse TSGCT harbor CSF1 fusion, targetable by imatinib, emactuzumab, and nilotinib, cases with malignant transformation (MTSGCT) have not responded to CSF1-R inhibitors. MTSGCT is at least an intermediate grade sarcoma of histiocytic phenotype of the knee, the majority with untoward outcome. Histologic criteria have been established for malignant transformation of diffuse TSGCT. Further studies are ongoing to identify possible alternate targets to CSF1-R in rare MTSGCT."

Clinical • Giant Cell Tumor of Bone • Oncology • Sarcoma • Tenosynovial Giant Cell Tumor • CD163 • CD34 • CD68 • CSF1 • HMGA2 • NCOR2 • PTPRC

A PHASE 3 MULTI-CENTER, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO ASSESS THE EFFICACY AND SAFETY OF EMACTUZUMAB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR (TANGENT) (CTOS 2022) - P3 | "There are currently no worldwide approved systemic therapies available for the treatment of patients with TGCT. Emactuzumab demonstrated a favorable risk-benefit profile in early phase clinical studies without the need of chronic and/or daily treatment, which has been recognized to be important for the future treatment of TGCT. The efficacy and safety of emactuzumab in patients with TGCT will be further assessed in the Phase 3 TANGENT trial.References1."

Clinical • P3 data • Giant Cell Tumor of Bone • Hematological Disorders • Hepatology • Immunology • Musculoskeletal Pain • Oncology • Orthopedics • Pain • Tenosynovial Giant Cell Tumor

Extensile Anterior and Posterior Knee Exposure for Complete Synovectomy of Diffuse Tenosynovial Giant Cell Tumor (Pigmented Villonodular Synovitis). (PubMed, JBJS Essent Surg Tech) - "Systemic agents such as tyrosine kinase inhibitors (e.g., nilotinib and imatinib) or agents targeting the CSF-1 (colony-stimulating factor-1) pathway (e.g., pexidartinib and emactuzumab) are active against TGCT. This will also reduce the risk of a postoperative nerve palsy.Although separate instruments for the anterior and posterior portions of the procedure are not necessary, separate drapes, gown, and gloves and other preoperative preparation should be readied in advance for the second portion of the procedure in order to save operative time. PVNS = pigmented villonodular synovitisROM = range of motionMRI = magnetic resonance imagingGastroc = gastrocnemiusPDS = polydioxanone sutureCAM = controlled ankle motionASA = acetylsalicylic acid (aspirin)."

Journal • Anesthesia • Fibrosis • Giant Cell Tumor of Bone • Immunology • Oncology • Orthopedics • Osteoarthritis • Pain • Rheumatology • Sarcoma • Solid Tumor • Tenosynovial Giant Cell Tumor • CSF1

Paclitaxel and Bevacizumab With or Without Emactuzumab in Treating Patients With Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P2 | N=9 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Sep 2022 | Trial primary completion date: May 2025 ➔ Sep 2022

Trial completion • Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor

TANGENT: Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT) (clinicaltrials.gov) - P3 | N=128 | Active, not recruiting | Sponsor: SynOx Therapeutics Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Giant Cell Tumor of Bone • Immunology • Oncology • Tenosynovial Giant Cell Tumor

Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade (BMJ) - P1b | N=221 | NCT02323191 | Sponsor: Hoffmann-La Roche | "No MTD was reached and the OBD was determined at 1000 mg of emactuzumab in combination with 1200 mg of atezolizumab....The confirmed objective response rate (ORR) was 9.8% for ICB-naïve UBC, 12.5% for ICB-experienced NSCLC, 8.3% for ICB-experienced UBC and 5.6% for ICB-experienced MEL patients, respectively. Tumor biopsy analyses demonstrated increased activated CD8 +tumor infiltrating T lymphocytes (TILs) associated with clinical benefit in ICB-naïve UBC patients and less tumor-associated macrophage (TAM) reduction in ICB-experienced compared with ICB-naïve patients."

P1 data • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Urothelial Cancer

"#SynOxTherapeutics reported #Emactuzumab designated as an #OrphanMedicinal Product in Europe https://t.co/rKE1OKOIXZ" (@1stOncology)

Emactuzumab designated as an Orphan Medicinal Product in Europe (PRNewswire) - "SynOx Therapeutics Limited...announces a regulatory update on emactuzumab, in development for the treatment of Tenosynovial Giant Cell Tumour (TGCT) and other diseases. The European Medicines Agency (EMA) has designated emactuzumab as an orphan medicinal product in the indication of TGCT for both localized and diffuse types of the disease....'We are now recruiting patients on to our phase III registrational trial (TANGENT) and look forward to providing an update on progress in the near future.'"

European regulatory • Trial status • Giant Cell Tumor of Bone • Oncology • Solid Tumor • Tenosynovial Giant Cell Tumor

TANGENT: Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT) (clinicaltrials.gov) - P3 | N=128 | Recruiting | Sponsor: SynOx Therapeutics Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Giant Cell Tumor of Bone • Immunology • Oncology • Tenosynovial Giant Cell Tumor