CT041 CAR-T Therapy for Stomach and Pancreatic Cancer

Not currently recruiting at 20 trial locations

Overseen By Julia Carnevale

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Carsgen Therapeutics, Ltd.

Must not be taking: Anticoagulants, Antiplatelets, Steroids

Disqualifiers: Pregnancy, HIV, Hepatitis, 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 tests a new treatment called CT041, which uses CAR-T immune cell therapy to target certain digestive system cancers, such as advanced stomach and pancreatic cancer. The main goal is to determine if this treatment can effectively shrink tumors that express the protein claudin18.2. The trial will assess different doses to identify the most effective one for these cancers. Suitable candidates for this trial include those who have advanced gastric or pancreatic cancer, have specific tumor characteristics, and have not responded to other treatments. Participants should also be in generally good health, with no active infections or severe health issues. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you require certain medications like anticoagulants, long-term antiplatelet therapy, or prednisone at 10mg or more daily. Additionally, you should not have had anticancer treatment within approximately 2 weeks before certain trial procedures.

Is there any evidence suggesting that CT041 CAR-T therapy is likely to be safe for humans?

Research has shown that CT041 CAR-T therapy, which targets a protein called claudin18.2, generally has a manageable safety profile. Most patients have found the side effects tolerable. In studies involving patients with advanced digestive system cancers, CT041 was usually well-tolerated. Some side effects occurred, but they were considered manageable. These results are encouraging, especially for those who have not had success with other treatments. While side effects can vary, evidence suggests that CT041 is a safe option for people with certain stomach and pancreatic cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CT041 CAR-T therapy because it offers a novel approach to treating stomach and pancreatic cancer. Unlike traditional treatments like chemotherapy and radiation, CT041 uses chimeric antigen receptor (CAR) T-cells engineered to specifically target and eliminate cancer cells expressing the claudin18.2 protein. This targeted action could potentially lead to more effective treatment with fewer side effects, as it aims to directly attack cancer cells while sparing healthy tissue. Additionally, by focusing on this unique protein marker, CT041 might provide a new option for patients with advanced gastric cancer who have limited choices with current therapies.

What evidence suggests that CT041 might be an effective treatment for stomach and pancreatic cancer?

Research shows that CT041 CAR-T therapy, which participants in this trial will receive, could be promising for treating advanced stomach and pancreatic cancers. Previous studies found that this treatment effectively targets a protein called claudin18.2, present in these cancers. In patients who had already tried other treatments, CT041 showed very positive results and was generally well-tolerated. Some patients even experienced a complete response, meaning their cancer was no longer detectable after treatment. These findings suggest CT041 could be a good option for people with these hard-to-treat cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Harry H Yoon, MD

Principal Investigator

Mayo

Dae Won Kim, MD

Principal Investigator

Moffitt

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with advanced gastric or pancreatic cancer, who have tried other treatments without success. They must not be pregnant, have HIV/HBV/HCV, uncontrolled infections, significant heart/lung/neurological disorders, autoimmune diseases, a second cancer besides STAD/PAAD or previous cell therapies/transplants.

Inclusion Criteria

Your doctor thinks you will live for more than 4 months.

Voluntarily signed the ICF

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

Exclusion Criteria

I need blood-thinning medication like warfarin or heparin.

I have another type of cancer besides stomach or pancreatic cancer.

My cancer has significantly affected my lungs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Manufacturing

Patients undergo leukapheresis to collect autologous mononuclear cells for the manufacture of the investigational drug product (CT041)

4 weeks

Preconditioning and CT041 Infusion

Participants receive preconditioning treatment followed by CT041 infusion

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 15 years

Long-term Gene Safety Follow-up

All subjects will be asked to continue to undergo long-term gene safety follow-up

up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• CT041

Trial Overview The study tests CT041 CAR-T cells targeting claudin18.2 in patients with specific digestive cancers. It's an early-phase trial to assess safety and effectiveness of this therapy in those whose tumors express CLDN18.2 and who've failed standard treatments.

How Is the Trial Designed?

Group I: anti-claudin18.2 chimeric antigen receptor T-cell therapy Experimental Treatment 1 Intervention

Phase 1b will include two parts, dose escalation phase (Cohort A) followed by a dose expansion phase (Cohort B). Phase 2 (Cohort C) will evaluate the chosen dose in patients with advanced gastric cancer.

Who Is Running the Clinical Trial?

Carsgen Therapeutics, Ltd.

Lead Sponsor

Trials

8

Recruited

640+

CARsgen Therapeutics Co., Ltd.

Lead Sponsor

Trials

33

Recruited

3,100+

Published Research Related to This Trial

Adoptive cell therapy using CAR-engineered T cells shows promise as a safe treatment option for patients with pancreatic ductal adenocarcinoma, indicating it may help restore effective immune surveillance against tumors.

Early results suggest that CAR T cells not only have the ability to attack tumors directly but also stimulate the body's own immune system to fight cancer, enhancing overall anti-tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. Beatty, GL.[2023]

Pancreatic cancer is projected to become the second leading cause of cancer-related deaths in the U.S. by 2030, highlighting the urgent need for new treatment options, as current immunotherapies have shown limited effectiveness.

Chimeric antigen receptor (CAR) T cell therapy is emerging as a promising treatment for pancreatic cancer, utilizing genetically engineered T cells to target specific cancer-associated antigens, with ongoing preclinical and early clinical trials exploring its efficacy and potential combinations with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential of CAR T Cell Therapy in Pancreatic Cancer. Akce, M., Zaidi, MY., Waller, EK., et al.[2022]

In a phase 1 clinical trial involving 37 patients with CLDN18.2-positive digestive system cancers, CT041 CAR T cell therapy demonstrated a promising overall response rate of 48.6% and a disease control rate of 73.0%.

The treatment showed an acceptable safety profile, with all patients experiencing grade 3 or higher hematologic toxicity but no severe cytokine release syndrome or neurotoxicities, indicating that CT041 could be a viable option for patients with previously treated gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Qi, C., Gong, J., Li, J., et al.[2022]

A novel combination therapy using dual-specific CAR T-cells targeting Her2 and gp100, along with a vaccinia virus vaccine and the histone deacetylase inhibitor panobinostat, effectively eradicated tumors in murine models of pancreatic cancer.

The treatment not only induced cancer cell death but also enhanced the CAR T-cells' ability to develop into long-lasting memory cells, suggesting a promising approach for future pancreatic cancer therapies in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Histone Deacetylase Inhibitor, Panobinostat, Enhances Chimeric Antigen Receptor T-cell Antitumor Effect Against Pancreatic Cancer. Ali, AI., Wang, M., von Scheidt, B., et al.[2022]

Pancreatic cancer is highly aggressive with a low 5-year survival rate of about 10%, and current treatments are limited, highlighting the urgent need for effective therapies.

While CAR T cell therapy has shown success in blood cancers, its effectiveness in pancreatic cancer is still limited; ongoing research is exploring strategies like enhancing CAR T cells and using alternative immune cells to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The next wave of cellular immunotherapies in pancreatic cancer. Yeo, D., Giardina, C., Saxena, P., et al.[2022]

CAR-T cell therapy demonstrated promising response rates in various solid cancers, with a median overall response of 62% across 15 clinical trials involving 159 patients, including 100% in ovarian epithelial cancer and 82% in advanced gastric/pancreatic cancer.

The therapy was well-tolerated, with only one reported case of cytokine release syndrome, indicating a favorable safety profile as it is evaluated for use in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Role of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in the Treatment of Solid Tumors. Siddiqui, RS., Sardar, M.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2501

Final results of CT041-CG4006 phase 1 trial. Satri-cel/CT041 demonstrated a promising safety profile and highly encouraging efficacy in heavily pretreated patients with CLDN18.2-positive advanced GI ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04404595

NCT04404595 | Claudin18.2 CAR-T (CT041) in Patients ... This is an open label, multi-center, Phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous claudin18.2 chimeric antigen receptor ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625000164

The high efficacy of claudin18.2-targeted CAR-T cell ... The present study showed the robust anti-tumor activity of claudin18.2-targeted CAR-T cells against PC and reported the feasibility of the antibody-dependent ...

4. nature.com nature.com/articles/s41591-022-01800-8

Claudin18.2-specific CAR T cells in gastrointestinal cancers These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10860094/

Metastatic gastric cancer target lesion complete response with ... We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4017

Safety, tolerability, and preliminary efficacy results in ... These preliminary results suggest that CT041 had manageable safety/tolerability profile and promising efficacy in patients with previously treated advanced G/ ...

7. jitc.bmj.com jitc.bmj.com/content/12/2/e007927

Metastatic gastric cancer target lesion complete response ... We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04581473

NCT04581473 | Study to Evaluate the Efficacy, Safety and ... Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell Injection. ClinicalTrials.gov ID NCT04581473. Sponsor CARsgen ...