FDA Grants Fast Track Designation to Emactuzumab for Unresectable TGCT

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The FDA has granted fast track designation to the CSF-1R–inhibiting monoclonal antibody emactuzumab for the treatment of patients with tenosynovial giant cell tumor (TGCT) who are not amenable to or who would not benefit from surgery.1

Previously reported data from a phase 1 study (NCT01494688) demonstrated that patients with diffuse-type TGCT treated with emactuzumab (n = 63) achieved an overall response rate (ORR) of 71%, including a complete response rate of 3% and a partial response rate of 68%.2 Twenty-seven percent of patients had stable disease, none had progressive disease, and 2% were not evaluable for response.

Regarding safety, adverse effects (AEs) led to treatment discontinuation in 14% of patients, and no deaths were associated with AEs. The most AEs comprised pruritus (70%), asthenia (39%), face oedema (49%), peripheral oedema (44%), periorbital oedema (43%), and eyelid oedema (37%).

The agent is being further evaluated in the phase 3 TANGENT trial (NCT05417789), where patients with unresectable TGCT are being randomly assigned to receive emactuzumab or placebo.1,3

“The granting of fast track designation for emactuzumab in TGCT highlights the devastating toll that this disease has on patients, as well as the critical need that remains for new treatment options,” Elyse Seltzer, MD, chief medical officer of SynOx Therapeutics, stated in a news release. “Based on our clinical work to date, we believe that emactuzumab has significant potential to address key patient needs by offering an effective, short-course treatment with rapid onset and a durable response that allows individuals suffering from TGCT to better manage their disease and move forward with their lives. We look forward to completing the ongoing TANGENT study and progressing emactuzumab toward potential commercialization."

TANGENT is a multicenter, randomized, double-blind, placebo-controlled study enrolling patients at least 12 years of age with biopsy-confirmed local or diffuse TGCT who are not candidates for surgery if resection would be associated with predicted worsening functional limitations through surgical joint damage; and/or an anticipated high risk of early recurrence per multidisciplinary tumor board or equivalent assessment, or any other morbidity associated with the surgery; and/or are not expected to achieve improved clinical outcomes with surgery.3

Other key inclusion criteria consist of measurable disease with a longest diameter of at least 20 mm; and adequate organ and bone marrow function.

Patients with metastatic TGCT or another active cancer requiring concurrent or planned treatment are not allowed to enroll. Treatment with another CSF-1– or CSF-1R–targeted therapy, or another multi-kinase inhibitor, are not permitted within 3 months of enrollment. Surgery, chemotherapy, or radiotherapy within 3 months of enrollment are also disallowed.

In part 1 of the study, patients are being randomly assigned to receive emactuzumab or placebo. Patients in both arms are receiving treatment on day 1 of cycle 1, then once every 2 weeks for a total of 5 doses, followed by a 3-month observation period to close the 24-week first part of the study. In part 2, all patients—including those given placebo in part 1—will be allowed to receive open-label emactuzumab once every 2 weeks for a total of 5 doses.

ORR at 6 months is serving as the trial’s primary end point. Secondary end points include physical function, range of motion, worst stiffness, worst pain, quality of life, duration of response, tumor volume score, and surgical intervention rate.

The ongoing study is expected to enroll approximately 128 patients globally, and has a target primary completion date of April 30, 2026.

References

1. SynOx Therapeutics receives fast track designation from U.S. Food and Drug Administration for emactuzumab for tenosynovial giant cell tumours (TGCT). News release. SynOx Therapeutics. April 14, 2025. Accessed April 14, 2025. https://synoxtherapeutics.com/synox-therapeutics-receives-fast-track-designation-from-u-s-food-and-drug-administration-for-emactuzumab-for-tenosynovial-giant-cell-tumours-tgct/
2. 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
3. Study of emactuzumab for tenosynovial giant cell tumor (TGCT) (TANGENT). ClinicalTrials.gov. Updated February 19, 2025. Accessed April 14, 2025. https://clinicaltrials.gov/study/NCT05417789