TL118 for Solid Tumors

Recruiting at 19 trial locations

Overseen By Dawei Zhang

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Teligene US

Must not be taking: Chemotherapy, Immunotherapy, TCMs, others

Disqualifiers: Active CNS metastases, Other malignancies, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests TL118, an experimental pill, to evaluate its effectiveness for people with solid tumors that have a specific gene change called an NTRK fusion. The goal is to determine if TL118 can slow or stop tumor growth. Participants must have a confirmed diagnosis of a solid tumor with this gene fusion and have experienced tumor growth despite previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have had any systemic anti-tumor therapy, like chemotherapy or radiation, within 3 weeks before joining the trial.

Is there any evidence suggesting that TL118 is likely to be safe for humans?

Research shows that TL118 consists of several active ingredients already approved for use. These ingredients have undergone testing and are generally considered safe for humans. In earlier studies, TL118 was designed to cut off the blood supply to tumors, potentially aiding in cancer treatment.

Although detailed information on side effects for TL118 in solid tumors is not available, the approval of its components offers some reassurance about its safety. This trial is in Phase 2, indicating that earlier studies have shown the treatment to be safe. However, participants should remain aware of any possible side effects and report them to their doctors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TL118 because it offers a novel approach to treating solid tumors. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, TL118 targets specific pathways involved in tumor growth, potentially reducing harmful side effects. Additionally, TL118 is taken orally as a capsule, making it more convenient for patients compared to some existing treatments that require intravenous administration. This new mechanism and delivery method could make TL118 a game-changer in cancer treatment.

What evidence suggests that TL118 might be an effective treatment for solid tumors?

Research has shown that TL118 may help treat certain solid tumors with specific gene changes called NTRK fusions. In previous studies, TL118 helped patients live longer and slowed tumor spread. It also slowed the growth of aggressive tumors, whether used alone or with another drug, Gemcitabine. Combining TL118 with other treatments proved more effective than using each drug individually. These findings suggest that TL118 could benefit people with certain solid tumors. Participants in this trial will receive TL118 alone to evaluate its effectiveness. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific gene fusion called NTRK1/2/3. Participants must have tried other treatments without success or be unsuitable for standard care, and should not have used TRK inhibitors before (except briefly due to side effects). They need to be relatively active (ECOG score 0-2) and expected to live more than 3 months.

Inclusion Criteria

Additional requirements must be fulfilled for participation in the Study.

My blood, liver, kidney, and clotting tests are within normal ranges.

My cancer is advanced, has a specific gene change but no other major cancer-driving mutations.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TL118 capsule taken orally, 252 mg twice daily, for 28 days per cycle

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TL118

Trial Overview The study tests the effectiveness of TL118, an investigational drug in capsule form, on patients with solid tumors containing NTRK gene fusions. The goal is to see how well TL118 works against these types of cancers.

How Is the Trial Designed?

Group I: Single arm, Open label Experimental Treatment 1 Intervention

Participants will receive TL118 capsule taken orally with (preferred) or without food, 252 mg twice daily, 28 days for a cycle.

Who Is Running the Clinical Trial?

Teligene US

Lead Sponsor

Trials

3

Recruited

230+

Published Research Related to This Trial

Epithelioid sarcoma (EpS) is a rare and aggressive soft-tissue cancer primarily affecting young people, with a high fatality rate of about 50% despite current treatments like surgery and chemotherapy.

The recent approval of the EZH2 inhibitor tazemetostat as a targeted therapy for EpS has not significantly improved outcomes for most patients, highlighting the urgent need for new treatment strategies and the formation of a collaborative research community to advance understanding and therapy development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational Aspects of Epithelioid Sarcoma - Current Consensus. Grünewald, TGP., Postel-Vinay, S., Nakayama, RT., et al.[2023]

CPT-11 demonstrated significant tumor growth inhibition in 8 out of 15 human ovarian cancer lines and 6 out of 10 human soft-tissue sarcoma lines when administered at a daily dose of 20 mg/kg for five days.

The study suggests that more frequent administration of lower doses of CPT-11 may enhance its effectiveness in clinical settings, as the drug showed better results with a daily schedule compared to a weekly one, despite higher doses being used in the latter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma. Jansen, WJ., Kolfschoten, GM., Erkelens, CA., et al.[2019]

FL118, a novel anticancer compound identified through high throughput screening, effectively inhibits cancer cell growth at very low concentrations (less than nM) and works independently of p53 status, making it a promising treatment option for various cancers.

In vivo studies demonstrated that FL118 has superior antitumor efficacy compared to several standard chemotherapy agents, leading to tumor regression in human tumor xenograft models, while also showing manageable side effects like temporary body weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel small molecule FL118 that selectively inhibits survivin, Mcl-1, XIAP and cIAP2 in a p53-independent manner, shows superior antitumor activity. Ling, X., Cao, S., Cheng, Q., et al.[2021]

EZN-2208, a PEGylated form of the topoisomerase inhibitor SN38, was found to be generally well-tolerated in a Phase 1 study involving 30 children with relapsed or refractory solid tumors, with a maximum tolerated dose identified at 24 mg/m².

The treatment showed preliminary antitumor activity, particularly in neuroblastoma, where two out of nine evaluable patients experienced partial responses, indicating potential clinical benefit for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 evaluation of EZN-2208, a polyethylene glycol conjugate of SN38, in children adolescents and young adults with relapsed or refractory solid tumors. Norris, RE., Shusterman, S., Gore, L., et al.[2018]

In patients with metastatic colorectal cancer, there is a significant decrease in certain lymphocyte populations (CD3+CD4+, CD8+CD28+, and CD19+) and an increase in activated T-cells and specific monocytes, indicating an altered immune response.

Treatment with CPT-11 (irinotecan) for 2-4 months led to a significant increase in CD3+CD4+ cell counts in patients with initially low levels, suggesting that this chemotherapy may help counteract the immunosuppressive effects of the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of irinotecan on the phenotype of peripheral blood leukocyte populations in patients with metastatic colorectal cancer. Melichar, B., Touskova, M., Vesely, P.[2018]

FL118, a new camptothecin analogue, shows superior antitumor efficacy compared to existing treatments like irinotecan and topotecan, effectively overcoming resistance in human tumor models.

Unlike traditional camptothecins, FL118's effectiveness does not depend on the expression level of the Top1 protein, suggesting that its antitumor activity may not primarily involve Top1 inhibition, although it does share similar hematopoietic toxicity mechanisms with other CPTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topoisomerase I (Top1): a major target of FL118 for its antitumor efficacy or mainly involved in its side effects of hematopoietic toxicity? Li, F., Ling, X., Harris, DL., et al.[2020]

A new combination treatment strategy using the CDK4/6 inhibitor palbociclib shows promise for treating Rb-positive soft tissue sarcomas by inducing cell cycle arrest, making the cancer cells more sensitive to other treatments like doxorubicin.

This synergistic effect was confirmed in both laboratory tests and in vivo studies using patient-derived xenografts, providing strong preclinical support for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest. Francis, AM., Alexander, A., Liu, Y., et al.[2022]

FL118 is a promising new anticancer drug that targets multiple resistance mechanisms by inhibiting several antiapoptotic proteins and inducing pro-apoptotic proteins, making it effective even in cancers with dysfunctional p53, which are typically resistant to many treatments.

Unlike traditional chemotherapy drugs like irinotecan and topotecan, FL118 is not affected by the ABCG2 efflux pump, allowing it to maintain efficacy in cancer cells that express high levels of this pump, which often leads to resistance against other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer drug FL118 is more than a survivin inhibitor: where is the Achilles' heel of cancer? Li, F.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06010342

A Study to Evaluate the Efficacy and Safety of TL118 ... The main objective of the study will be to evaluate the efficacy of TL118 in participants with solid tumors harboring NTRK gene fusions.

2. withpower.com withpower.com/trial/phase-2-neoplasms-2024-935fa

TL118 for Solid Tumors Trial Overview The study tests the effectiveness of TL118, an investigational drug in capsule form, on patients with solid tumors containing NTRK gene fusions.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3419965/

Improved efficacy of a novel anti-angiogenic drug ... This study demonstrated an unequivocal advantage to TL-118 therapy by significantly prolonging survival (threefold) and reducing metastasis perfusion and ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0090224

TL-118 and Gemcitabine Drug Combination Display ... To conclude, we demonstrate that the novel drug combination TL-118 has the ability to suppress the growth of an aggressive NB tumor. The promising results with ...

5. researchgate.net researchgate.net/figure/TL-118-treatment-composition-and-regimen_tbl1_229159488

TL-118 treatment composition and regimen | Download Table The synergistic effect of these drugs in combination was more effective than either TL or Gemcitabine alone (n = 9), via significantly reduced ...

6. trial.medpath.com trial.medpath.com/clinical-trial/6679c9bffda45d79/clinical-trial-anti-angiogenic-drug-combination-tl-118-pancreatic-cancer

A Clinical Trial of Anti-Angiogenic Drug Combination Tl-118 ... TL-118 is an anti-angiogenic drug combination designed for the treatment of cancer. The investigational product Tl-118 comprises of four well-known active ...