Emactuzumab for Giant Cell Tumor

(TANGENT Trial)

Not currently recruiting at 54 trial locations

Overseen By Clinical Team Synox

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: SynOx Therapeutics Limited

Must not be taking: Immunosuppressants, Antiretrovirals, Tyrosine kinase inhibitors

Disqualifiers: Pregnancy, Metastatic cancer, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, emactuzumab, to determine its effectiveness for people with TGCT, a condition that causes tumors in joints and soft tissues. These tumors can be difficult to remove surgically, so the study explores whether this medication offers a better option. Participants will receive either the actual drug or a placebo (a harmless substance with no therapeutic effect) and may switch to the real drug if eligible. Suitable candidates have TGCT that is not easily treatable with surgery and experience issues like limited movement due to the tumor. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic immunosuppressive medications (like glucocorticoids) at least 4 weeks before starting and during the study. If you are on systemic therapy for TGCT or certain other treatments, you must stop them 3 months before screening.

Is there any evidence suggesting that emactuzumab is likely to be safe for humans?

Research has shown that emactuzumab has been safe in earlier studies. For patients with tenosynovial giant cell tumor (TGCT), previous research found that emactuzumab was generally well-tolerated. In one study, 71% of patients had a significant positive response to the treatment, suggesting the drug could be effective with a manageable safety profile.

Most patients handled the treatment well, though some experienced mild to moderate side effects, which is common in clinical trials. This means there might be some discomfort, but serious side effects were not typical. Emactuzumab's progression to a late-stage trial (Phase 3) indicates that earlier phases found it safe enough for broader testing.

Overall, for those considering joining a trial for emactuzumab, current data suggest it has been safe for many patients. However, as with any medical treatment, individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Emactuzumab is unique because it targets the CSF1R (colony-stimulating factor 1 receptor), which plays a crucial role in the development of giant cell tumors. Most treatments for giant cell tumors focus on surgery or radiation, but emactuzumab offers a novel approach by specifically blocking the signals that cause these tumors to grow. This targeted action not only promises to be more effective but might also reduce the side effects associated with more traditional therapies. Researchers are excited about the potential of emactuzumab to provide a new, more precise treatment option for patients with this challenging condition.

What evidence suggests that emactuzumab might be an effective treatment for TGCT?

Research has shown that emactuzumab, which participants in this trial may receive, may help treat tenosynovial giant cell tumor (TGCT), especially when surgery isn't possible. In a study with TGCT patients, 71% experienced a noticeable decrease in tumor size, indicating that the drug helped shrink the tumors in most people who used it. Emactuzumab blocks specific pathways that help tumors grow. These findings suggest that emactuzumab could be an effective treatment option for people with TGCT. ^{2 3 5 6 7}

Who Is on the Research Team?

Jean Y Blay, Prof, MD

Principal Investigator

Comprehensive Cancer Centre of Lyon

Are You a Good Fit for This Trial?

This trial is for individuals over 12 with TGCT where surgery could worsen joint function or has high recurrence risk, and who can't have improved outcomes from surgery. Participants need proper organ/bone marrow function, a negative pregnancy test for women of childbearing age, and must agree to use effective contraception.

Inclusion Criteria

My biopsy shows TGCT that could worsen my joint function or recur quickly.

I am older than 12 years.

If a woman of childbearing potential, must have a negative pregnancy test prior to starting treatment and agree to use a highly effective method of contraception

Exclusion Criteria

I have had heart or lung problems in the last 6 months.

I have a history of liver disease.

Pregnant or breastfeeding female

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive emactuzumab or placebo intravenously every 2 weeks for a total of 5 doses, followed by an observation period

24 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with options for open-label retreatment or crossover

up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Emactuzumab

Trial Overview

The study tests emactuzumab's effectiveness and safety in treating TGCT when surgery isn't an option. It's a double-blind trial comparing emactuzumab with placebo given as an IV every two weeks for five sessions, followed by observation and long-term follow-up phases.

How Is the Trial Designed?

Group I: Group 1 in Part 1/Part 2: Emactuzumab Experimental Treatment 1 Intervention

Group 1: Subjects receiving emactuzumab administered intravenously (i.v) on Day(D)1 and repeated once every two weeks (Q2W) for a total of 5 times, followed by an observation period of 3 months leading to a total period of 24 weeks in Part 1 and continued with a follow-up phase in Part 2. Eligible Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment in Part 2.

Group II: Group 2 in Part 1 and Part 2: Placebo Placebo Group 1 Intervention

Group 2: Subjects receiving placebo administered intravenously (i.v) on D1 and repeated once every two weeks (Q2W) for 5 times followed by an observation period of 3 months to a total period of 24 weeks in Part 1. In Part 2, Eligible Subjects will have the option to receive open-label emactuzumab, administered by i.v once every 2 weeks (Q2W) for a total of 5 times.

Who Is Running the Clinical Trial?

SynOx Therapeutics Limited

Lead Sponsor

Trials

1

Recruited

130+

Published Research Related to This Trial

Denosumab, a monoclonal antibody approved for treating aggressive giant cell tumors of bone, was evaluated in a study of 30 patients, showing significant clinical benefits when used as a neoadjuvant therapy, with a 63.6% objective response rate in that group.

Patients receiving neoadjuvant denosumab experienced substantial symptom relief, including pain reduction and improved bladder and bowel functions, indicating its effectiveness in managing symptoms associated with sacral giant cell tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic benefits of neoadjuvant and post-operative denosumab on sacral giant cell tumor: a retrospective cohort study of 30 cases. Chen, Z., Yang, Y., Guo, W., et al.[2019]

Denosumab is effective in treating giant cell tumors (GCT) of the spine, providing pain relief and sometimes reducing tumor volume, making it a valuable option when traditional surgery is too risky or leads to significant functional loss.

In a cohort of 10 patients treated with Denosumab, there were no local recurrences after gross total excision followed by postoperative treatment, suggesting that Denosumab can enhance surgical outcomes and may be beneficial as a preoperative treatment as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab in the treatment of giant cell tumor of the spine. Preliminary report, review of the literature and protocol proposal. Boriani, S., Cecchinato, R., Cuzzocrea, F., et al.[2021]

In a study of 63 patients with diffuse-type tenosynovial giant-cell tumour (dTGCT), treatment with emactuzumab showed a high overall response rate of 71%, indicating significant clinical activity over a follow-up period of up to 2 years.

The treatment was associated with a manageable safety profile, with common side effects including pruritus, asthenia, and edema, while also leading to improvements in quality of life as measured by standard questionnaires.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical activity, safety and patient-reported quality of life for emactuzumab-treated patients with diffuse-type tenosynovial giant-cell tumour. Cassier, PA., Italiano, A., Gomez-Roca, C., et al.[2021]

Denosumab treatment in 15 patients with giant cell tumor of bone (GCTB) led to a significant reduction in tumor proliferation and angiogenesis, indicating its efficacy in managing this type of tumor.

The treatment resulted in the disappearance of osteoclast-like giant cells and a partial maturation of neoplastic cells towards an osteoblastic phenotype, suggesting a mechanism of action that may involve RANKL pathways, although immunophenotypical changes were minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. Girolami, I., Mancini, I., Simoni, A., et al.[2022]

In a pilot study of 8 central giant cell lesion (CGCL) specimens, 37.5% were found to have clinically relevant genomic alterations (CRGAs), including oncogenic mutations in genes like BRAF, GNAS, and KRAS.

The presence of somatic mutations that may activate the mitogen-activated protein kinase signaling pathway in 25% of the samples suggests this pathway could be a key driver of the aggressive behavior of CGCLs, indicating potential targets for personalized therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Genomic Profiling of Central Giant Cell Lesions Identifies Clinically Relevant Genomic Alterations. Bezak, B., Lehrke, H., Elvin, J., et al.[2017]

Emactuzumab, a monoclonal antibody targeting CSF1R, was found to be safe and well-tolerated in a phase 1 study involving 25 patients with diffuse-type tenosynovial giant cell tumor (dt-GCT), with no dose-limiting toxicities reported during the dose-escalation phase.

The treatment showed promising efficacy, with 86% of patients achieving an objective response and 7% achieving a complete response, indicating that emactuzumab could be a viable therapeutic option for this rare disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Cassier, PA., Italiano, A., Gomez-Roca, CA., et al.[2022]

In a study of 37 patients with recurrent or unresectable giant-cell tumors (GCT), 86% of evaluable patients showed a significant tumor response after treatment with denosumab, a monoclonal antibody targeting RANKL, indicating its potential efficacy in managing GCT.

While adverse events were common, with 33 out of 37 patients reporting issues, only one serious event was possibly related to the treatment, suggesting that denosumab has a manageable safety profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Thomas, D., Henshaw, R., Skubitz, K., et al.[2022]

Denosumab, a human monoclonal antibody that inhibits RANK ligand (RANKL), effectively impairs the growth of giant cell tumors of bone (GCTB), which are aggressive tumors that cause significant bone destruction.

Treatment with denosumab has been shown to reduce the extent of surgical intervention needed for GCTB and improve functional outcomes for patients, highlighting its potential as a valuable therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Denosumab may be a supplement to the surgical treatment of giant cell tumours of bone]. Sørensen, AL., Hansen, RL., Jørgensen, PH.[2022]

Denosumab, a medication used for treating giant cell tumor of bone, has been associated with a risk of clinically significant hypercalcemia after the treatment is stopped.

Healthcare providers should be aware of this risk and monitor patients for hypercalcemia following discontinuation of denosumab to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MHRA Drug Safety Update: denosumab (Xgeva) and rebound hypercalcaemia. [2019]

Citations

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A multicenter, randomized, double-blind phase III study to evaluate the safety and efficacy of Emactuzumab compared to placebo in patients with ...

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The approach recommended an optimal biological dose of emactuzumab for dosing every 2 weeks (q2w) ≥ 900 mg, approximately three-fold lower than the highest ...

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PK/PD Mediated Dose Optimization of Emactuzumab, a ...

This study used PK/PD data obtained from and open‐label, multicenter phase Ia/Ib study of emactuzumab (NCT01494688) that investigated the safety, PK, and ...