TST003 for Cancer

Not currently recruiting at 2 trial locations

Overseen By Lei Chen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Suzhou Transcenta Therapeutics Co., Ltd.

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

Disqualifiers: CNS metastases, Cardiovascular disease, Infections, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called TST003 for cancer patients. It aims to determine the safe dosage, understand the drug's duration in the body, and identify any side effects. The trial will also assess if patients' cancers respond to TST003. Participants will receive the drug every three weeks through an IV. This trial may suit individuals with advanced cancer that has not responded to other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had any systemic anti-cancer treatment within 4 weeks before starting the trial drug.

Is there any evidence suggesting that TST003 is likely to be safe for humans?

Research has shown that TST003 has a promising safety record in early studies. In animal tests, TST003 was well-tolerated after both single and repeated doses, suggesting potential safety for humans, though further research is necessary.

In human studies, TST003 was tested for safety in individuals with advanced solid tumors. Some participants experienced side effects like myelosuppression, where the bone marrow produces fewer blood cells. This can be a common side effect of certain cancer treatments.

As TST003 remains in the early testing stages, researchers are working to determine the safest dose and understand the drug's duration in the body. This information will help ensure TST003 is as safe as possible for patients who might benefit from it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TST003 because it is designed to specifically target tumors with positive GREM1 expression, which sets it apart from current cancer treatments that may not be as selective. Unlike traditional chemotherapy that attacks both cancerous and healthy cells, TST003 aims to zero in on cancer cells, potentially reducing side effects and improving patient outcomes. Furthermore, TST003 is administered every three weeks, offering a potentially more convenient dosing schedule compared to some existing treatments that require more frequent administration.

What evidence suggests that TST003 might be an effective treatment for cancer?

Research has shown that TST003 yields promising results in early tests. In studies with mice, TST003 significantly slowed the growth of prostate cancer tumors. This trial is studying TST003, which targets a protein called GREMLIN1 often found in certain cancer cells. Participants will receive TST003 every three weeks, either at increasing doses or at the recommended Phase 2 dose. Although more research is needed, these findings suggest TST003 could be effective against certain cancers. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults with certain advanced solid tumors, measurable lesions (for Phase Ib), and no standard treatment options left. They must be in good general health with proper organ function, not pregnant or nursing, and willing to use contraception. People who've had recent cancer treatments or severe illnesses are excluded.

Inclusion Criteria

My cancer has worsened despite treatment and there are no standard treatments left.

My liver tests for bilirubin, ALT, and AST are within normal limits.

I agree to use birth control during and 90 days after treatment.

Exclusion Criteria

I have brain metastases but haven't needed steroids for them in the last 4 weeks.

My heart's electrical activity (QT interval) is longer than normal or I have risk factors for irregular heartbeat.

I have had serious bleeding in my stomach or intestines in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2-4 visits (in-person)

Dose Escalation

Participants receive TST003 intravenously at increasing doses every 3 weeks to determine the recommended Phase 2 dose

Varies based on dose escalation schedule

Several visits after each dose for safety evaluations

Dose Expansion

Participants receive TST003 at the recommended Phase 2 dose every 3 weeks to assess efficacy and safety

Up to 1 year

Regular visits for assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TST003

Trial Overview TST003 is being tested for safety in cancer patients. The study will determine the safe dosage level, how long it stays in the body, side effects experienced by participants, and if it helps shrink their tumors. It's given intravenously every three weeks as long as benefits continue.

How Is the Trial Designed?

Group I: Phase 1b Part - Dose Expansion at Recommended Phase 2 dose Experimental Treatment 1 Intervention

Administer TST003 every 3 weeks to patients with positive GREM1 tumor expression at the recommended Phase 2 Dose,

Group II: Phase 1a Part - TST003 Dose Escalation Experimental Treatment 1 Intervention

TST003 administered every 3 weeks at increasing doses 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg

Who Is Running the Clinical Trial?

Suzhou Transcenta Therapeutics Co., Ltd.

Lead Sponsor

Trials

9

Recruited

1,700+

Published Research Related to This Trial

In a safety investigation involving 3,882 patients starting TS-1 therapy, the overall incidence of adverse reactions was 74.3%, with high rates of myelosuppression and gastrointestinal disorders, indicating significant side effects associated with this treatment.

The study highlighted the importance of safety monitoring and collaboration between healthcare providers to ensure proper patient eligibility and regular laboratory testing, which proved effective in managing the risks of serious adverse reactions during the early marketing period of TS-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Example of safety measures for antineoplastic agents immediately after market launch--a case of TS-1 capsule all example use result investigation that executes safety monitoring--]. Ito, K.[2019]

In a study of 67 patients with inoperable and recurrent gastric cancer, TS-1 therapy demonstrated a clinical efficacy with an overall response rate of 41%, particularly effective for peritoneal dissemination (57.1% response rate).

The treatment was found to be safe, with only 12.8% of patients experiencing severe adverse reactions (grade 3 or 4), and it resulted in a median survival time of 276 days, with notable long-term survival cases exceeding 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of TS-1 for inoperative and recurrent gastric cancer and evaluation of long survival cases]. Tanabe, K., Yoshida, K., Hamai, Y., et al.[2013]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05731271

A First-in-Human, Phase 1 Study of TST003 in Subjects ... The goal of this clinical trial is to test the safety of TST003 in patients with cancer. The main question[s] it aims to answer are:.

2. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/5977/739003/Abstract-5977-A-first-in-human-open-label-multi

A first-in-human, open-label, multi-center phase 1 study of ... This study will investigate TST003's safety, tolerability, and preliminary anti-tumor activity in patients with advanced solid tumors.

3. transcenta.com transcenta.com/ch/uploadfile/yushangweb_file/202404071451116612425fc75df.pdf

PowerPoint 演示文稿 The results (B) indicated that 10mg/kg TST003 significantly inhibited tumor growth and had a better anti-tumor activity when combo with DC101. Figure 3. CRPC ...

4. researchgate.net researchgate.net/publication/369810146_Abstract_465_The_preclinical_characterization_of_TST003_a_first-in-class_mAb_targeting_gremlin-1_overexpressed_by_cancer-associated_fibroblasts_and_tumor_cells

Abstract 465: The preclinical characterization of TST003, a ... ... Preclinical data demonstrate that TST003 exhibits promising efficacy as a monotherapy in Patient-Derived Xenograft (PDX) mouse models of human prostate and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12025430/

The Role of GREMLIN1, a Bone Morphogenetic Protein ... Preclinical data for Ginisortamab demonstrated that this antibody could reduce lung cancer cell proliferation in vitro [82]. Transcenta have developed TST003, a ...

6. transcenta.com transcenta.com/pipelineDet/id-6.html

TST003-TRANSCENTA HOLDING - A Global Fully ... TST003 is a first-in-class and high affinity humanized monoclonal antibody targeting GREMLIN-1, a regulatory protein that is highly expressed by stromal cells ...

7. withpower.com withpower.com/trial/phase-2-neoplasms-1-2023-c4018

TST003 for Cancer · Info for Participants TS-1 has been studied for safety in various cancers, showing a high incidence of adverse reactions like myelosuppression (reduced bone marrow activity) and ...

8. transcenta.com transcenta.com/Scientific_Publications/id-118.html

The Preclinical Characterization of TST003, a First-in-Class ... TST003 displayed excellent tolerability and safety profiles in NHP in single and repeated dose toxicity studies following i.v. administration. •These data ...