TST001 for Cancer

Not currently recruiting at 20 trial locations

Overseen By Angela Ireland, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mabspace Biosciences (Suzhou) Co., Ltd.

Must not be taking: CLDN18.2 agents

Disqualifiers: CNS metastases, Severe cardiovascular disease, Concurrent malignancy, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, TST001, for individuals with advanced or hard-to-treat cancers, including certain stomach and pancreatic cancers. The goal is to evaluate how well TST001 works alone or with other treatments like nivolumab. The trial includes different groups based on previous treatments and cancer types. Suitable candidates include those with advanced stomach or pancreatic cancer that cannot be surgically removed and has not improved with standard treatments. Participants must have their cancer confirmed by a medical professional and meet specific health criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that TST001 is likely to be safe for humans?

Research has shown that TST001, a treatment being tested for various types of cancer, appears promising in terms of safety. In one study, TST001 combined with nivolumab was safe and well tolerated by patients with stomach cancer. In this study, patients received TST001 at a dose of 6 mg/kg every three weeks.

Other studies have also examined the safety of TST001 in patients with different solid tumors. These studies found that TST001 is generally well tolerated, with most people not experiencing severe side effects. However, as this is a new treatment, ongoing research is crucial to fully understand its safety.

It is important to note that TST001 remains in the early stages of testing. Researchers continue to learn about its effects and any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for gastrointestinal and pancreatic cancers, TST001 is unique because it is a monoclonal antibody that specifically targets CLDN18.2, a protein often overexpressed in these cancers. This targeted approach could potentially improve treatment precision and effectiveness by honing in on cancer cells without affecting healthy tissues as much. Researchers are excited about TST001 because its novel mechanism of action may offer new hope for patients, especially those with advanced or resistant forms of these cancers, who have limited options with current therapies like chemotherapy and radiation.

What evidence suggests that TST001 might be an effective treatment for advanced and/or metastatic solid tumors?

Research shows that TST001, a monoclonal antibody, holds promise for treating certain cancers. In this trial, participants with stomach or gastroesophageal junction (G/GEJ) cancer will receive TST001 in different cohorts. Previous studies have shown that combining TST001 with chemotherapy and nivolumab has led to positive outcomes, such as tumor reduction and improved patient conditions. One study even found that one patient showed no signs of cancer after treatment, while others experienced tumor shrinkage. For pancreatic cancer, where the protein Claudin 18.2 is often abundant, early results suggest TST001 might also be effective. This indicates that TST001 could become an important treatment option for these challenging cancers. ^{3 4 5 6 7}

Who Is on the Research Team?

Charlie Qi, MD

Principal Investigator

Suzhou Transcenta Therapeutics Co.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including stomach, gastroesophageal junction, and pancreatic cancers. Participants must have tried standard treatments without success or be unable to tolerate them. They should be in good physical condition (ECOG PS: 0-1) and not have severe heart disease, recent strokes or heart attacks, active infections like hepatitis B/C or HIV/AIDS.

Inclusion Criteria

My cancer is advanced and has been confirmed by lab tests.

I have untreated advanced pancreatic cancer, but may have had prior therapy if my cancer returned 6 months after treatment ended.

My heart, liver, and kidneys are functioning well.

Exclusion Criteria

I have never been treated with CLDN18.2 targeting drugs.

I haven't had another cancer within the last 5 years, except for certain treated types.

Documented history of multiple other allergies requiring interventions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding (Part A)

Participants receive TST001 in a 3+3 design to determine the dose, dosed every 2 or 3 weeks

Up to 12 weeks

Bi-weekly or tri-weekly visits

Treatment (Part B)

Participants receive TST001 in combination with Nivolumab or standard of care in different cohorts

Up to 24 months

Bi-weekly or tri-weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 days following last dose

What Are the Treatments Tested in This Trial?

Interventions

• TST001

Trial Overview TST001 is being tested alone or with other cancer drugs (Nivolumab or standard care chemotherapies) for safety and effectiveness against certain advanced cancers. This trial includes different patient groups based on prior treatment history and specific cancer types.

How Is the Trial Designed?

Group I: Part B Cohort C Experimental Treatment 3 Interventions

Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma.

Group II: Part B Cohort B Experimental Treatment 2 Interventions

Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies.

Group III: Part B Cohort A Experimental Treatment 3 Interventions

Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma.

Group IV: Part A Q3W Experimental Treatment 1 Intervention

Dosed every 3 weeks IV with TST001, starting dose is 3 mg/kg, and multiple dose levels will be tested.

Group V: Part A Q2W Experimental Treatment 1 Intervention

Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, multiple dose levels will be tested.

Who Is Running the Clinical Trial?

Mabspace Biosciences (Suzhou) Co., Ltd.

Lead Sponsor

Trials

5

Recruited

580+

Suzhou Transcenta Therapeutics Co., Ltd.

Lead Sponsor

Trials

9

Recruited

1,700+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Imatinib mesylate has shown a high clinical response rate of 81.6% in patients with gastrointestinal stromal tumors (GIST), with 53.7% achieving a partial response and 27.9% having stable disease.

While most patients experienced only mild toxicities (grade 1 or 2), 21.1% had more severe side effects (grade 3 or higher), indicating that imatinib is relatively safe but can still cause significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of imatinib for gastrointestinal tumor]. Mizunuma, N.[2015]

A study analyzing 8512 individual case safety reports found that neuropsychiatric adverse drug reactions (ADRs) occurred in 17.8% of cases involving tyrosine kinase inhibitors (TKIs) for gastrointestinal stromal tumors, with avapritinib showing a higher reporting probability for these ADRs.

Notably, avapritinib was associated with rare neuropsychiatric ADRs such as lumbar spinal cord disorders, olfactory nerve disorders, and hallucinations, indicating the need for further research to better understand these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System. Barbieri, MA., Sorbara, EE., Russo, G., et al.[2023]

In a study of 470 Japanese patients with imatinib-resistant or intolerant gastrointestinal stromal tumors, sunitinib demonstrated good efficacy with a 20% objective response rate and a median progression-free survival of 22.4 weeks.

The treatment was generally well-tolerated, with 70% of patients experiencing grade ≥ 3 adverse events, but specific early adverse events like hand-foot syndrome and leukopenia were linked to improved progression-free survival, indicating they may serve as positive prognostic markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor. Komatsu, Y., Ohki, E., Ueno, N., et al.[2022]

A review of 81 clinical trials involving over 45,000 patients revealed that the reporting of adverse events (AEs) for targeted therapies and immunotherapies is often inadequate, particularly regarding recurrent/late toxicities and the duration of AEs.

The study highlights that more than 90% of trials failed to adequately report the timing and occurrence of all-grade AEs, indicating a need for improved transparency and detail in AE reporting in future oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Bossi, P., Botta, L., Bironzo, P., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4048

First-line osemitamab (TST001) plus nivolumab and capox ... The combination of TST001 6mg/kg Q3W plus nivolumab and CAPOX for the 1 st line treatment of patients with G/GEJ cancer is safe and well tolerated.

2. asco.org asco.org/abstracts-presentations/ABSTRACT378342

A phase I study of TST001, a high affinity humanized anti- ... Conclusions: Conclusion: TST001 in combination with CAPOX in first line gastric cancer patients is safe and encouraging anti-tumor activities have been observed ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2949819825000792

The prognostic role of Claudin 18.2 in advanced gastric or ... This SLR evaluated associations of CLDN18.2 expression with outcomes of interest in advanced G/GEJ adenocarcinoma. •. Main outcomes were patient ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10951399/

Dark horse target Claudin18.2 opens new battlefield for ... The results were found that among the 11 evaluable individuals one had CR who had a gastric adenocarcinoma, three had partial response (PR) (two ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS4176

A multi-cohort phase I/IIa clinical trial to evaluate the safety, ... Conclusions: Combination of TST001 with nivolumab and chemotherapy has the potential to improve the outcomes of patients with advanced or ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04396821

Study Details | NCT04396821 | A Trial to Evaluate Safety ... Cohort A is for patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma. Patients will receive TST001 at 2mg/kg ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT354399

A phase I clinical trial to evaluate the safety, tolerability ... A phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of TST001 in patients with locally advanced or metastatic solid tumors.