Breakthrough Emactuzumab Phase 3 TANGENT Trial in TGCT: SynOx Pharma Reports Enrollment Completed Ahead of Schedule

August 05, 2025 | Dublin, Oxford, and Philadelphia – SynOx Therapeutics Limited today announced the completion of patient enrollment in the registrational Phase 3 TANGENT trial evaluating emactuzumab in patients with Tenosynovial Giant Cell Tumor (TGCT) not amenable to surgery. Enrollment concluded significantly ahead of schedule, with top-line results expected in the first quarter of 2026.

“Completion of enrollment in our registrational TANGENT trial marks an important milestone for SynOx and for the TGCT community”

said Elyse Seltzer, M.D., Chief Medical Officer of SynOx Therapeutics.

“We are extremely grateful to the patients, families, investigators, and clinical sites whose dedication made this achievement possible and allowed us to enroll the study well ahead of schedule. Subject to data, we remain committed to providing a much-needed new treatment option for this challenging condition.” 

LinkedIn photo of Elyse Seltzer

Ray Barlow, Chief Executive Officer of SynOx, said,

“This is an exciting and transformative time for SynOx as we move emactuzumab through its pivotal Phase 3 program. We are enthusiastic about the upcoming steps and look forward to top-line results that we hope will highlight emactuzumab’s potential to significantly improve care for patients affected by this serious disease.” 

LinkedIn photo of Ray Barlow

About the TANGENT Trial

The TANGENT study (NCT05417789) is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial designed to assess the efficacy and safety of emactuzumab.
Patients were randomized in a 2:1 ratio to receive either emactuzumab (1000 mg every two weeks for five doses) or placebo.

• Primary endpoint: Objective Response Rate (ORR) by RECIST criteria at six months.
• Key secondary endpoints: patient-reported outcomes (PROMIS-PF), joint function (range of motion, pain, stiffness), durability of response, and safety.

Patients will be followed for two years, with those showing progression eligible to switch to open-label emactuzumab.

FDA Grants Fast Track Designation to Emactuzumab in TGCT

In April 2025, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to emactuzumab, a CSF-1R–targeting monoclonal antibody, for the treatment of patients with unresectable tenosynovial giant cell tumor (TGCT). The designation underscores the significant unmet medical need for effective therapies in patients for whom surgery is not feasible or unlikely to provide meaningful benefit.

The decision is supported by data from a phase 1 clinical trial (NCT01494688) involving 63 patients with locally advanced or relapsed TGCT. Emactuzumab demonstrated a 71% overall response rate (ORR) by RECIST criteria and 86% by tumor volume score, with a median time to response of 2 months. Responses were durable in many patients, with continued benefit observed for over 12 months. Patients also experienced clinically meaningful improvements in joint pain, stiffness, mobility, and overall quality of life.

Emactuzumab was generally well tolerated, with the most common adverse events being pruritus, fatigue, edema, and rash. Grade ≥3 events were infrequent, and no treatment-related deaths were reported. Treatment discontinuation due to adverse events occurred in 14% of patients, most often associated with transient liver enzyme elevations.

Read more information on SynOx Therapeutics Official Website.

What is Emactuzumab and How does it Work?

Emactuzumab is a humanized IgG1 monoclonal antibody developed by SynOx Therapeutics (originally in-licensed from Roche) that selectively targets the colony-stimulating factor 1 receptor (CSF-1R). The drug is designed to address the underlying biology of tenosynovial giant cell tumor (TGCT), a disease driven by overproduction of CSF-1, which recruits and maintains an abnormal population of tumor-associated macrophages (TAMs) in the synovial tissue. These macrophages contribute to joint inflammation, tumor growth, and functional impairment.
By binding to CSF-1R, emactuzumab blocks CSF-1 signaling, leading to the depletion of TAMs in the tumor microenvironment. This targeted immune modulation results in:

• Tumor shrinkage, by removing the macrophage support that drives growth.
• Symptom relief, including reduced pain, stiffness, and improved joint mobility.
• Durable responses, as the disruption of TAM-driven pathology addresses a root cause of disease progression.

Unlike conventional therapies that target tumor cells directly, emactuzumab works by modifying the tumor microenvironment, highlighting its potential as a precision therapy for macrophage-driven disorders such as TGCT.

What is Tenosynovial Giant Cell Tumor?

Tenosynovial Giant Cell Tumor (TGCT) is a rare, usually benign tumor affecting the synovium, the tissue lining joints and tendons. It arises from excessive proliferation of synovial cells and is driven by a chromosomal translocation that overproduces colony-stimulating factor-1 (CSF-1), recruiting macrophages to the tumor. TGCT is classified into two forms:

• Localized TGCT (Giant Cell Tumor of Tendon Sheath): Often a slow-growing, painless mass, typically in the fingers or hands. It is the second most common hand tumor after ganglion cysts.
• Diffuse TGCT (Pigmented Villonodular Synovitis – PVNS): Less common but more aggressive, usually affecting larger joints like the knee. It can cause swelling, pain, stiffness, and, if untreated, joint damage.

Although benign, TGCT can severely limit joint function and mobility. It mostly affects adults aged 25–50, with slightly higher incidence of localized TGCT in females. The global incidence is estimated at 43 cases per 1 million people, with localized TGCT being more frequent.
Symptoms typically include pain, swelling, tenderness, and joint instability. Diagnosis often requires imaging, such as X-rays or MRI, and sometimes a biopsy to distinguish TGCT from other joint conditions.

Treatment Options for TGCT

Surgery is the standard treatment for TGCT, but recurrence is common, particularly in diffuse cases. For patients who are not surgical candidates or experience relapse, targeted therapies offer alternatives. These include pexidartinib (Turalio), imatinib (Gleevec), and more recently, Vimseltinib (Romvimza). Vimseltinib has primarily been studied as a monotherapy in TGCT and some advanced solid tumors, showing promising efficacy and tolerability in early trials. Ongoing research, including studies like MOTION, is evaluating its safety, long-term outcomes, and potential future combinations with other therapies.