Intratumoral Tigilanol Tiglate for Soft Tissue Sarcoma

Overseen By Head of Human Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: QBiotics Group Limited

Must not be taking: Warfarin

Disqualifiers: Brain metastases, Major surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called tigilanol tiglate (also known as Stelfonta or EBC-46) for individuals with advanced or spreading soft tissue sarcoma—a cancer affecting muscles, fat, or other soft tissues. The treatment involves injecting the tumor directly to determine if it shrinks or disappears. Eligible participants should have soft tissue sarcoma that can be felt or seen with ultrasound and is located on the body or limbs. This trial offers a chance to try a new approach that could help manage the disease. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires a 28-day period without taking any systemic anticancer therapy or investigational agents before starting the study treatment. This means you may need to stop certain medications, but it's best to discuss your specific situation with the study team.

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

Research has shown that tigilanol tiglate is generally safe for patients. In one study, 11 patients received the treatment and tolerated it well, experiencing no severe side effects. Another study found that tigilanol tiglate could serve as a good alternative to surgery, as patients managed the treatment well when injected directly into tumors. Reports confirm that tigilanol tiglate appears safe for individuals with soft tissue sarcoma, a type of cancer that forms in soft tissues. Overall, evidence suggests this treatment is safe for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for soft tissue sarcoma?

Tigilanol tiglate is unique because it directly targets tumors through intratumoral injections, delivering the treatment right where it's needed. This contrasts with traditional systemic therapies for soft tissue sarcoma, which often involve chemotherapy that circulates throughout the body. Researchers are excited about tigilanol tiglate because it has a novel mechanism of action that prompts the tumor cells to self-destruct while also activating the immune system to help clear the tumor. This localized approach could reduce side effects and improve the precision of treatment, potentially offering a more effective and gentler option for patients.

What evidence suggests that tigilanol tiglate might be an effective treatment for soft tissue sarcoma?

Research has shown that tigilanol tiglate holds promise for treating soft tissue sarcoma. In studies, this treatment reduced tumor size in patients, with 80% experiencing significant shrinkage. Tigilanol tiglate met its primary objectives in these studies, demonstrating expected efficacy. Overall, evidence suggests that tigilanol tiglate could offer hope for people with this type of cancer. Participants in this trial will receive single or multiple intratumoral injections of tigilanol tiglate. ^{1 3 4 5 6}

Who Is on the Research Team?

Edmund Bartlett, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced soft tissue sarcoma in limbs or body wall, able to consent and follow study rules. They must have a life expectancy over 12 weeks, be relatively active (ECOG ≤ 2), and not pregnant or breastfeeding. Participants need functioning kidneys and liver, agree to use contraception, and can't have major blood vessel tumors or recent treatments that conflict with the trial.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

Willing and able to provide written informed consent for the study prior to any protocol-specific procedures and to comply with all local and study requirements

My cancer is on the body wall or limbs and can be injected directly.

Exclusion Criteria

I plan to have direct tumor treatment or radiation within 28 days before screening or while on tigilanol tiglate.

My tumor is near or has spread into a major blood vessel.

I haven't had major surgery in the last 28 days and don't expect to need any during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single or multiple intratumoural injections of tigilanol tiglate at up to a fixed dose of 3.6 mg/m2

6 months

Multiple visits for injections and assessments

Follow-up

Participants are monitored for safety, efficacy, and local recurrence rate after treatment

6 months

Regular follow-up visits for monitoring

Pharmacokinetic Assessment

Evaluation of systemic exposure and metabolite analysis after a single intratumoural injection

24 hours

1 visit for blood sampling

What Are the Treatments Tested in This Trial?

Interventions

• Tigilanol Tiglate

Trial Overview The trial is testing Tigilanol Tiglate's effectiveness when injected directly into tumors of patients with advanced soft tissue sarcomas. It's an open-label Phase IIa study meaning everyone gets the treatment and both doctors and participants know what's being given.

How Is the Trial Designed?

Group I: Single Arm, Open Label Experimental Treatment 1 Intervention

Single or multiple Intratumoural injections of tigilanol tiglate at up to a fixed dose of 3.6 mg/m2 (Body Surface Area \[BSA\]) per treatment.

Tigilanol Tiglate is already approved in European Union, United States for the following indications:

Approved in European Union as Stelfonta for:

• Non-resectable, non-metastatic subcutaneous mast cell tumors located at or distal to the elbow or the hock, and non-resectable, non-metastatic cutaneous mast cell tumors in dogs

Approved in United States as Stelfonta for:

• Non-metastatic, skin-based (cutaneous) mast cell tumors (MCTs) and non-metastatic MCTs located under the dog's skin (subcutaneous), in particular areas of a dog's leg

Who Is Running the Clinical Trial?

QBiotics Group Limited

Lead Sponsor

Trials

4

Recruited

80+

Published Research Related to This Trial

The designer peptide [D]-K3H3L9 showed significant cytotoxic and antiproliferative effects against soft tissue sarcoma cell lines in vitro, indicating its potential as an effective treatment option.

In vivo studies in athymic and syngeneic mouse models demonstrated that intratumoral administration of [D]-K3H3L9 significantly inhibited tumor progression and exhibited antiangiogenic properties, suggesting a promising therapeutic mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of soft tissue sarcoma growth by a host defense-like lytic peptide. Steinstraesser, L., Hauk, J., Schubert, C., et al.[2021]

In a study involving 36 patients with advanced soft tissue sarcoma, edatrexate showed a partial response rate of 14%, with notable effectiveness in patients with malignant fibrous histiocytoma (MFH), where 5 out of 7 patients experienced a partial response.

While the overall activity of edatrexate was limited, it was generally well-tolerated, with mild myelosuppression and manageable side effects like fatigue and rash, suggesting that further research is needed, particularly for MFH patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edatrexate in patients with soft tissue sarcoma. Activity in malignant fibrous histiocytoma. Casper, ES., Christman, KL., Schwartz, GK., et al.[2019]

Ecteinascidin (ET-743) demonstrated promising antitumor activity in patients with advanced soft tissue sarcoma, achieving an 8% partial response rate and a 56% progression arrest rate in specific sarcoma types, indicating its potential effectiveness as a second- or third-line treatment.

The treatment was associated with manageable safety concerns, primarily reversible liver enzyme elevations and neutropenia, with no cumulative toxicities observed, and a median overall survival of 9.2 months in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. Le Cesne, A., Blay, JY., Judson, I., et al.[2018]

In a study of 11 patients with sarcoma, nanosomal docetaxel lipid suspension (NDLS) chemotherapy showed promising efficacy, with a 50% overall response rate and a 66.7% disease control rate in metastatic cases, indicating its potential effectiveness in treating this type of cancer.

NDLS-based chemotherapy was well tolerated, with no new safety concerns identified, although 63.6% of patients experienced at least one adverse event, primarily hematological and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study. Narayanan, P., Dattatreya, PS., Prasanna, R., et al.[2022]

Ecteinascidin-743 (ET-743) demonstrated antitumoral activity in advanced soft tissue sarcoma patients, with a 4% overall response rate and a 24% disease progression control rate at 6 months, indicating some effectiveness in a challenging patient population.

The treatment had a manageable safety profile, although 50% of patients experienced significant liver enzyme elevations and 61% had severe neutropenia, with two treatment-related deaths occurring due to complications likely linked to protocol violations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. Yovine, A., Riofrio, M., Blay, JY., et al.[2018]

Citations

1. onclive.com onclive.com/view/tigilanol-tiglate-shows-early-efficacy-in-soft-tissue-sarcomas

Tigilanol Tiglate Shows Early Efficacy in Soft Tissue ... Data from the first stage of a phase 2a study suggest that tigilanol tiglate reduced tumor volume in patients with soft tissue sarcoma.

2. targetedonc.com targetedonc.com/view/promising-efficacy-for-tigilanol-tiglate-in-advanced-soft-tissue-sarcoma

Promising Efficacy for Tigilanol Tiglate in Advanced Soft ... A phase 2a trial shows tigilanol tiglate achieves an 80% response rate in soft tissue sarcoma, offering hope for effective treatment options.

3. qbiotics.com qbiotics.com/announcement/qbiotics-reports-80-objective-response-rate-in-injected-tumours-in-stage-1-of-phase-iia-clinical-trial-of-tigilanol-tiglate-for-soft-tissue-sarcoma

QBiotics reports 80% objective response rate in injected ... Tigilanol tiglate met both its primary and secondary endpoints and delivered patients an impressive 80% Objective Response Rate in injected tumours.

4. cancernetwork.com cancernetwork.com/view/tigilanol-tiglate-exhibits-positive-efficacy-in-soft-tissue-sarcoma

Tigilanol Tiglate Exhibits Positive Efficacy in Soft Tissue ... Efficacy data revealed that among 10 efficacy evaluable patients in the stage I pilot trial, the objective response rate (ORR) was 80%, with ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03347-7/fulltext

1736P An open label phase IIa study evaluating the ... Intratumoural TT appears safe for patients with STS. Efficacy in ablating injected tumours was observed across different histologic types. The primary endpoint ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6921293/

Phase I dose-escalation study to determine the safety ... Tigilanol tiglate possesses antitumor activity and appears to be effective and well tolerated when injected intralesionally as an alternative to surgery.