The phase 3 TANGENT trial (NCT05417789) has met its primary and secondary end points, with emactuzumab (RG-7155) showing statistically significant improvements in overall response rate (ORR) per RECIST 1.1 criteria and tumor volume score (TVS) vs placebo at 6 months, as well as clinically meaningful improvements in patient-reported functional measures, in adult patients with tenosynovial giant cell tumor (TGCT).1
This benefit was consistent with emactuzumab’s differentiated profile. Patient-reported and functional outcomes included physical function (PROMIS-PF), pain, range of motion, and stiffness. Of note, these benefits were rapidly achieved during short-course treatment, were durable, and were observed across clinically relevant patient groups.
Emactuzumab's safety profile was described as manageable and consistent with prior clinical experience. These data reinforce the agent's potential as a next-generation, short-course alternative to currently available chronic oral therapies, according to SynOx Therapeutics, the drug’s developer.
"The TANGENT results represent an important step in advancing a potential next-generation treatment for patients with TGCT," Raymond Barlow, PhD, chief executive officer of SynOx Therapeutics, stated in a news release. “Emactuzumab's combination of rapid onset, response rate, meaningful functional improvement, and a defined short-course regimen positions it as a potential alternative to chronic therapy, directly addressing key limitations of existing treatments.”
Based on these data, SynOx plans to submit a biologics license application to the FDA seeking the approval of emactuzumab for the treatment of patients with TGCT in the second half of 2026, with a European Union marketing authorization application to follow. The study will continue to follow enrolled patients to further characterize the durability of response and the potential for retreatment and crossover to open-label emactuzumab.
What is emacutuzumab’s mechanism of action?
The humanized monoclonal antibody emactuzumab is a potent and selective colony-stimulating factor 1 receptor (CSF-1R) antagonist that causes apoptosis of M2-type macrophages in the tumor microenvironment, thereby inhibiting tumor growth.1,2 By targeting the receptor through which CSF-1 drives macrophage recruitment and proliferation, emactuzumab addresses the underlying pathobiology of the tumor rather than acting as a cytotoxic agent. It is accordingly being developed as a short-course treatment for patients with TGCT and is designed to deliver rapid and durable disease control without the need for continuous treatment.1
What was the design of TANGENT?
TANGENT is a multicenter, phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of emactuzumab in patients with biopsy-confirmed localized or diffuse TGCT.2 Patients for whom surgical resection would be associated with potentially worse functional limitations, those at high risk of early recurrence, or patients with other morbidities were eligible for enrollment, and adolescent patients at least 12 years of age but no older than 18 were permitted to directly enter the open-label phase. Prior use of TKIs or CSF-1/CSF-1R–targeted therapies was also allowed, provided that there was a sufficient washout period.
TANGENT Trial Positions Emactuzumab as Short-Course TGCT Option
- The TANGENT trial met its primary and secondary end points, with a high level of statistical significance achieved with emactuzumab when compared with placebo at 6 months in patients with TGCT.
- Emactuzumab significantly improved ORR and TVS vs placebo at 6 months and resulted in rapid, durable, and clinically meaningful improvements in patient-reported outcomes, including physical function, pain, range of motion, and stiffness across subgroups.
- The safety profile was manageable and consistent with prior data, supporting emactuzumab’s potential as a short-course alternative to long-term oral therapies.
The study consists of two parts. In part 1, eligible patients are randomly assigned in a 2:1 ratio to receive either emactuzumab administered intravenously at a dose of 1000 mg or matching placebo once every 2 weeks for 5 cycles for a total of 10 weeks. Patients are stratified according to prior TKI therapy. Of note, patients were allowed to enter an 18-month follow-up phase after the 6-month double-blind period, during which patients who experienced signs of disease progression can receive open-label emactuzumab.1
The primary end point is ORR by RECIST 1.1 criteria at 6 months. Key secondary end points include PROMIS-PF, TVS, range of motion, pain, stiffness, quality of life, duration of response, and surgical intervention rate.1,2 The study planned to enroll approximately 128 patients across sites in the United States, Canada, Europe, and Asia.2
What prior data and regulatory updates have been reported with emacutuzumab?
Emacutuzumab previously demonstrated rapid, durable responses across a range of dose levels in patients with diffuse-type TGCT in a phase 1 study (NCT01494688).2 Among the 63 patients in this study, emactuzumab yielded an ORR of 71% for all dose levels, and 82% of patients who achieved a response did so within 3 months of starting treatment. The ORR was maintained at 70% and 64% after 1 and 2 years of follow-up, respectively. The optimal biological dose was identified as 1000 mg intravenously every 2 weeks. The most commonly observed adverse effects were grade 1/2 pruritus (70%), asthenia (62%), and facial edema (49%).
Based on these data, the FDA granted fast track designation to emactuzumab in April 2025 for the treatment of patients with unresectable TGCT, recognizing the significant unmet medical need in patients for whom surgery is not feasible or unlikely to provide meaningful benefit.3
The agent also received orphan medicinal product designation from the European Medicines Agency that same month.
Full datasets from the TANGENT trial are anticipated to read out at an upcoming medical meeting and be shared in a peer-reviewed publication.1
“Emactuzumab is the only short-course treatment option in late-stage development for patients…with TGCT,” Jean-Yves Blay, MD, a medical oncologist and general director of the Centre Leon Berard at the Comprehensive Cancer Centre of Lyon, France, as well as the principal investigator of TANGENT, concluded. “These phase 3 data provide compelling evidence of tumor response, a manageable safety profile, and most importantly for patients, of significant durable functional and quality of life benefits that allow patients struggling with TGCT to move forward with their lives without continuous therapy.”
References
- SynOx therapeutics announces positive topline results from the phase 3 TANGENT study, supporting emactuzumab as a differentiated, next-generation treatment for patients with tenosynovial giant cell tumor (TGCT). News Release. SynOx. April 13, 2026. Accessed April 13, 2026. https://synoxtherapeutics.com/synox-therapeutics-announces-positive-topline-results-from-the-phase-3-tangent-study/
- Gelderblom H, Palmerini E, Blay J-Y, et al. 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). J Clin Oncol. 2025;43(16 suppl):TPS11584. doi:10.1200/JCO.2025.43.16_suppl.TPS11584
- SynOx Therapeutics. SynOx Therapeutics receives fast track designation from U.S. Food and Drug Administration for emactuzumab for tenosynovial giant cell tumors (TGCT). News Release. SynOx. April 14, 2025. Accessed April 13, 2026. https://synoxtherapeutics.com/wp-content/uploads/2025/04/SynOx-Emactuzumab-FTD-PR-vFINAL.pdf
