Tenosynovial Giant Cell Tumor

P3, N=128, Recruiting, SynOx Therapeutics Limited | Trial primary completion date: Sep 2027 --> Apr 2026

Thorough clinical and radiological follow-up is mandatory as local recurrences are to be expected due to the infiltrative behavior. In case of a loco regional recurrence the fusion with FGFR2 may represent a therapeutic option for a targeted therapy on molecular level.

The patient was treated with pegylated interferon and imatinib, which resulted in stable disease after three months...Analysis of ligand-receptor interactions showed significant communication between neoplastic cells and macrophages mediated by CSF1 and CSF1R. Our findings emphasize the importance of comprehensive molecular analysis in diagnosing and treating rare malignancies like TGCT.

The case underscores the importance of considering MTB infection in the differential diagnosis of chronic unilateral knee arthritis, especially given the atypical clinical manifestations and imaging findings that can mimic other conditions like PVNS.

P2, N=21, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Nov 2026 --> May 2026

We conclude that these unusual tumors represent a distinct category of synoviocytic neoplasia, which we term "chondroid synoviocytic neoplasm", rather than simply ordinary TGCT with cartilage. Despite potentially worrisome morphologic features, they appear to behave in at most a locally aggressive fashion.

P1, N=85, Recruiting, Abbisko Therapeutics Co, Ltd | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P2, N=17, Active, not recruiting, Andrew J. Wagner, MD, PhD | Trial completion date: Jan 2025 --> Jul 2025

In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCT-like features and FN1::TEK fusions.

The final diagnosis for the knee nodule was pigmented villonodular synovitis. This case highlights the potential for pigmented villonodular synovitis to mimic MM, requiring additional pathologic analysis to yield an accurate diagnosis.

Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT whose disease is not amenable to surgery.

This study provides overall protein and gene profiles of PVNS and identifies the crucial role of TGF-β in synovial invasion pathology. Exploring the related molecular mechanism may also reveal a new strategy or target for PVNS therapy.

P2, N=20, Completed, AmMax Bio, Inc. | Recruiting --> Completed | N=48 --> 20 | Trial completion date: Jan 2026 --> Jun 2024 | Trial primary completion date: Nov 2025 --> Jun 2024

P2, N=11, Completed, AmMax Bio, Inc. | Active, not recruiting --> Completed

Due to histopathologic resemblance with other giant cell-rich lesions (giant cell granuloma of the jaws, brown tumor of hyperparathyroidism, and non-ossifying fibroma) for which signature mutations are known, mutational analysis of KRAS, FGFR1, and TRPV4 genes was conducted. The results revealed wild-type sequences for all the mutations tested, thereby supporting the diagnosis of tenosynovial giant cell tumor.

PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment for GCTST. In addition, we will discuss the differential diagnosis of this peculiar neoplasm.

P2, N=4, Terminated, AmMax Bio, Inc. | Active, not recruiting --> Terminated; Further enrollment was halted in November 2021, enrolled subjects completed the study. Sponsor stopped further recruitment in this intravenous study to focus on intra-articular route of administration in subjects with tenosynovial giant cell tumor.

P1/2, N=120, Active, not recruiting, Deciphera Pharmaceuticals LLC | Trial completion date: Jun 2024 --> Aug 2028 | Trial primary completion date: Dec 2023 --> Jul 2026

P3, N=128, Not yet recruiting, SynOx Therapeutics Limited | Trial completion date: Sep 2025 --> Sep 2027 | Trial primary completion date: Dec 2023 --> Sep 2027

P3, N=40, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Mar 2024 --> Feb 2026

P3, N=90, Active, not recruiting, Abbisko Therapeutics Co, Ltd | Recruiting --> Active, not recruiting

P3, N=120, Active, not recruiting, Deciphera Pharmaceuticals LLC | Trial primary completion date: Mar 2024 --> Aug 2023

P2, N=17, Active, not recruiting, Andrew J. Wagner, MD, PhD | Trial completion date: Jul 2024 --> Jan 2025

P3, N=90, Recruiting, Abbisko Therapeutics Co, Ltd

The results of immunoblotting assays suggested that silybinin as well as compound glycyrrhizin inhibited the protein expression of CYP3A4 and CYP2C9 in rats. Therefore, the combination of pexidartinib with silybinin and compound glycyrrhizin should be monitored to avoid clinical adverse effects.

In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

MMP9, SPP1, and TYROBP were identified as osteoclast-specific up-regulated genes of the tenosynovial giant cell tumour via bioinformatic analysis, which had a reasonable diagnostic efficiency and served as potential drug targets.

Our findings provide additional evidence that the CSF1/CSF1R pathway is involved in the pathogenesis of XGET/KPGCT. These findings suggest a possible role for CSF1R inhibition in the treatment of unresectable or metastatic XGET/KPGCT.

We identified the risk indicators and developed a nomogram in this study to forecast the likelihood of local recurrence-free survival in patients with diffused-tenosynovial giant cell tumor from temporomandibular joint.

P1/2, N=120, Active, not recruiting, Deciphera Pharmaceuticals LLC | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2022 --> Dec 2023

Careful consideration should be given to the differential diagnosis of pediatric patients presenting with monoarthritis. This report highlights the importance of early and accurate diagnosis and underscores the necessity for effective treatments for epithelioid sarcoma. Surgical resection or radical surgery is recommended, while novel treatment strategies targeting EZH2 show promise.

DOG1 is also useful in reinforcing a diagnosis of chondroblastoma in a clinicoradiological context, especially in laboratories lacking H3.3K36M immunostain. However, its staining pattern is variable.

TGCT can arise at the craniocervical junction and is easily misdiagnosed because of its rare occurrence. IHC examination of a tumor specimen should be done to confirm the diagnosis. GTR is the objective when treating these tumors, especially when they are the diffuse type, as they have a high recurrence rate. Radiation and small-molecule therapies are viable postoperative therapies if GTR cannot be achieved or in cases of recurrence.

For the first time, this paper was able to provide data on a large sample for Germany. Notably, the low sensitivity of the clinical diagnosis confirms the importance of histopathology for diagnosing L‑TSRZT.

In the current study, the metabolic activation of PEX was investigated in human/mouse liver microsomes (HLM/MLM) and primary human hepatocytes (PHH) using glutathione (GSH) and methoxyamine (NHOMe) as trapping reagents. CYP3A4 and CYP3A5 were identified as the primary enzymes responsible for the formation of these adducts using recombinant human P450s and CYP3A chemical inhibitor ketoconazole. Overall, our studies suggested that PEX metabolism can produce reactive metabolites mediated by CYP3A, and the association of the reactive metabolites with PEX hepatotoxicity needs to be further studied.

In Part 1, participants are randomized to receive vimseltinib 30 mg twice weekly or matching placebo for ≤24 weeks. Part 2 is a long-term treatment phase in which participants will receive open-label vimseltinib.

In Asian patients with symptomatic TGCT not amenable to improvement with surgery, pexidartinib demonstrated clinical benefit in tumor response and improvement in joint function. The overall safety profile of pexidartinib was comparable with previous data. Hepatotoxicity was manageable with frequent liver test monitoring and dose modifications as defined in the protocol, and no new safety signals were observed in this Asian population.

Pts with TGCT not amenable to surgery and no prior anti-CSF1/CSF1R therapy (previous treatment with imatinib or nilotinib was allowed) were enrolled and treated with vimseltinib 30 mg twice weekly (recommended phase 2 dose). Longer follow-up demonstrated that vimseltinib continued to be well tolerated with a manageable safety profile in pts with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy. Antitumor activity continued to improve with a promising overall ORR. At week 25, the majority of responders experienced ≥30% reductions in worst and average pain.

Pts with TGCT not amenable to surgery who received prior anti-CSF1/CSF1R therapy (including pexidartinib, cabiralizumab, or vimseltinib) were enrolled and treated with vimseltinib 30 mg twice weekly (recommended phase 2 dose). Longer follow-up demonstrated that vimseltinib continued to be well tolerated with a manageable safety profile in pts with TGCT not amenable to surgery who received prior anti-CSF1/CSF1R therapy. Antitumor activity continued to improve in this pretreated population, with an increased ORR. At week 25, all responders experienced ≥30% reductions in worst and average pain.