Emactuzumab Responses Yield Statistical Significance in Tenosynovial Giant Cell Tumor

Primary and secondary end points of the phase 3 TANGENT trial (NCT05417789) assessing emactuzumab were met with a high level of statistical significance compared with placebo for patients with tenosynovial giant cell tumor (TGCT), according to a press release from SynOx Therapeutics.¹

The primary end point was objective response rate (ORR) at 6 months measured by RECIST 1.1. The secondary end points detected the effect of emactuzumab on physical function, range of motion, stiffness, pain, and duration of response, which were measured by the tumor volume score, Patient-Reported Outcomes Measurement Information System Physical Function TGCT t score, range of motion, and assessments for pain, stiffness, and quality of life.

The press release also highlighted that emactuzumab in patients with TGCT demonstrated a manageable safety profile, which was consistent with previously reported data. Additionally, a sustained and durable clinical benefit was noted.

In 2026, SynOx Therapeutics plans to submit a biologics license application to the FDA and a European Medicines Agency marketing authorization application. Full data will be presented at an upcoming medical meeting.

“Emactuzumab is the only short-course treatment option in late-stage development for patients suffering with TGCT. These phase 3 data provide compelling evidence of tumor response, a manageable safety profile, and, most importantly for patients, significant durable functional and quality-of-life benefits that allow patients struggling with TGCT to move forward with their lives, without continuous therapy,” Jean-Yves Blay, MD, PhD, professor of medicine at the University Claude Bernard in Lyon, France; general director of the Centre Leon Berard, the Comprehensive Cancer Centre of Lyon; and principal investigator of the study, said in the press release.¹

At the 2025 American Society of Clinical Oncology Annual Meeting, the TANGENT study findings were presented during a poster session as a trial in progress. Patients were randomly assigned 2:1 to receive emactuzumab or placebo.² Patients were stratified by prior tyrosine kinase inhibitor (TKI) therapy.

An estimated 128 patients were enrolled and given 1000 mg of emactuzumab every 2 weeks for 5 doses over 8 weeks or placebo. Placebo dosing was matched.³

Patients 12 years or older but younger than 18 years could be enrolled and directly entered into the open-label portion of the study. Patients 12 years or older were permitted in the trial. Additionally, if patients had biopsy results–confirmed TGCT where surgical resection was associated with worse functioning and limitations, high risk of early recurrence, or any other morbidity, they were eligible for the study. Patients previously using TKIs or colony-stimulating factor 1(CSF-1)/CSF-1 receptor targeted therapy with a significant washout period was allowed.

Previous data with emactuzumab in this population showed an ORR of 71% for all dose levels.⁴ After 1-year follow-up, the ORR remained at 70%, and at 2 years, it was 64%. Adverse effects were grade 1/2 and included pruritus (70%), asthenia (62%), and facial edema (49%).

“The TANGENT results represent an important step in advancing a potential next-generation treatment for patients with TGCT,” Ray Barlow, CEO of SynOx Therapeutics, said in the press release.¹ “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. We believe this approach directly addresses key limitations of existing treatments and represents an important advancement for patients suffering from this debilitating disease. We look forward to engaging with the FDA as we advance toward a planned BLA submission in the second half of 2026.”

References

1. SynOx Therapeutics announces positive topline results from the phase 3 TANGENT study. News release. SynOx Therapeutics. April 13, 2026. Accessed April 14, 2026. https://tinyurl.com/36424wjr
2. Gelderblom H, Palmerini E, Blay JY, 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):TPS11584. doi:10.1200/JCO.2025.43.16_suppl.TPS11584
3. Study of emactuzumab for tenosynovial giant cell tumor (TGCT) (TANGENT). ClinicalTrials.gov. Updated February 2, 2026. Accessed April 14, 2026. https://tinyurl.com/2p7ruzrp
4. Cassier PA, Italiano A, Gomez-Roca C, et al. Long-term clinical activity, safety and patient-reported quality of life for emactuzumab-treated patients with diffuse-type tenosynovial giant-cell tumour. Eur J Cancer. 2020;141:162-170. doi:10.1016/j.ejca.2020.09.038