CT041 CAR-T Therapy for Stomach and Pancreatic Cancer

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

110 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 1b/2, open label, multi-center, clinical study of Chimeric Antigen Receptor T Cells (CAR-T) targeting claudin18.2 in patients with advanced gastric, pancreatic or other specified digestive system cancers

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.

What data supports the effectiveness of the CT041 CAR-T treatment for stomach and pancreatic cancer?

Research shows that CAR T cell therapy, which involves modifying a patient's own immune cells to better attack cancer, has shown promise in treating pancreatic cancer by targeting specific proteins on cancer cells and improving immune response. In studies, these engineered cells have been able to significantly reduce tumor size in pancreatic cancer models. ^{1 2 3 4 5}

Is CT041 CAR-T therapy safe for humans?

In a phase 1 trial of CT041 CAR-T therapy for digestive system cancers, all patients experienced some blood-related side effects, but no severe cytokine release syndrome (a condition where the immune system is overly activated) or neurotoxicities (nerve-related side effects) were reported. This suggests that CT041 has an acceptable safety profile in humans. ^{1 2 6 7 8}

What makes CT041 CAR-T treatment unique for stomach and pancreatic cancer?

CT041 CAR-T treatment is unique because it uses genetically engineered T cells to specifically target and attack cancer cells that express the Claudin18.2 protein, which is found in certain stomach and pancreatic cancers. This approach is different from traditional treatments as it harnesses the body's immune system to fight cancer, offering a novel option for patients with limited effective treatments. ^{1 3 6 9 10}

Research Team

Harry H Yoon, MD

Principal Investigator

Mayo

Dae Won Kim, MD

Principal Investigator

Moffitt

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Potential of CAR T Cell Therapy in Pancreatic Cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Redirected T cells that target pancreatic adenocarcinoma antigens eliminate tumors and metastases in mice. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pancreatic Cancer UK Grand Challenge: Developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Restored CD8+PD-1+ T Cells Facilitate the Response to Anti-PD-1 for Patients With Pancreatic Ductal Adenocarcinoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. [2022]

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

A Histone Deacetylase Inhibitor, Panobinostat, Enhances Chimeric Antigen Receptor T-cell Antitumor Effect Against Pancreatic Cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

The next wave of cellular immunotherapies in pancreatic cancer. [2022]