CAR T-cell Therapy for Stomach & Pancreatic Cancer

Recruiting at3 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Legend Biotech USA Inc

Must not be taking: Anticoagulants, Antiplatelets, Immunosuppressants

Disqualifiers: Cellular immunotherapy, Brain metastasis, HIV, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment using modified immune cells to target and kill cancer cells in patients with advanced stomach, esophagus, or pancreatic cancer. The treatment focuses on cancers that have a specific protein. The treatment targets a specific protein found on certain cancer cells and has shown promise in previous studies for treating advanced stomach and esophagus cancers. The study aims to find the best dose for future use.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude patients who require anticoagulant or long-term antiplatelet therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment LB1908, Satricabtagene autoleucel, satri-cel, CT041 for stomach and pancreatic cancer?

Research shows that CAR T-cell therapy, which is a type of treatment that uses specially modified immune cells to target cancer, has shown promise in early studies for pancreatic cancer. Some studies have demonstrated that this approach can lead to tumor reduction in animal models and has potential for further development in human trials. ^{1 2 3 4 5}

How is the treatment LB1908 different from other treatments for stomach and pancreatic cancer?

LB1908, a CAR T-cell therapy, is unique because it uses genetically engineered T cells to specifically target cancer cells, which is different from traditional treatments like chemotherapy that affect both cancerous and healthy cells. This approach is particularly novel for pancreatic cancer, where effective treatment options are limited. ^{1 4 6 7 8}

Research Team

Eligibility Criteria

Adults aged 18-75 with advanced stomach, GEJ, esophageal, or pancreatic cancer that's not operable and hasn't responded to standard treatments can join. They must have tried certain chemotherapies before and have CLDN18.2 positive tumors. Good organ function is required, they should be in decent physical shape (ECOG 0 or 1), expect to live at least four more months, and agree to use effective birth control for a year after treatment.

Inclusion Criteria

My cancer in the stomach, GEJ, or lower esophagus cannot be surgically removed and standard treatments are not suitable for me.

My organs are functioning well.

Presence of ≥ 1 radiologically measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

Exclusion Criteria

I need blood thinners like warfarin or heparin.

I have another type of cancer that doesn't meet the study's exceptions.

I do not have an active HIV, hepatitis B, or hepatitis C infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prescreening

Patients are confirmed to have sufficient expression of Claudin 18.2

2 weeks

Dose Escalation (Part A)

Patients with gastric, GEJ, or esophageal adenocarcinoma are treated with LB1908 at protocol-defined dose levels, with escalation to higher doses guided by evaluation of dose limiting toxicities

28 days

Dose Expansion (Part B)

Testing of the recommended dose for expansion in two cohorts: gastric, GEJ, and esophageal adenocarcinoma cohort and pancreatic adenocarcinoma cohort

90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Minimum of 2 years

Treatment Details

Interventions

• LB1908 (CAR T-cell Therapy)

Trial Overview The trial tests LB1908 cells designed to target Claudin 18.2 on cancer cells in patients with specific types of advanced gastrointestinal cancers. It's an early-phase study where researchers will try different doses to see what’s safe and might work.

Participant Groups

Group I: Experimental LB1908 Experimental Treatment 1 Intervention

Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells

LB1908 is already approved in China for the following indications:

Approved in China as Satricabtagene autoleucel for:

• Gastric adenocarcinoma
• Gastroesophageal junction adenocarcinoma

Who Is Running the Clinical Trial?

Legend Biotech USA Inc

Lead Sponsor

Trials

3

Recruited

150+

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]

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]

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]

This study identifies four promising tumor-specific antigens (CLA, CD66c, CD318, and TSPAN8) for CAR T cell therapy in pancreatic ductal adenocarcinoma (PDAC) after screening 371 antigens.

CAR T cells targeting CD318 and TSPAN8 showed significant efficacy in preclinical models, with CD318 leading to complete tumor eradication, suggesting these targets could be key for future clinical applications in PDAC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. Schäfer, D., Tomiuk, S., Küster, LN., et al.[2023]

The manufacturing process for lisocabtagene maraleucel (liso-cel), an autologous CAR T-cell therapy, has been optimized to ensure high product quality and consistency, even with diverse starting materials from patients with various hematologic malignancies.

Improvements in the manufacturing process led to over 95% T-cell purity and enhanced viability of the CAR T-cell product, demonstrating that liso-cel can effectively maintain its therapeutic potential despite variability in patient-derived materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing lisocabtagene maraleucel chimeric antigen receptor T-cell manufacturing for improved process, product quality and consistency across CD19+ hematologic indications. Teoh, J., Brown, LF.[2022]

In a phase 2 trial involving 111 patients with refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 82%, with 54% achieving a complete response, indicating its efficacy as a treatment option.

The treatment was associated with significant adverse events, including neutropenia in 78% of patients and neurologic events in 28%, highlighting the need for careful monitoring of safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. Neelapu, SS., Locke, FL., Bartlett, NL., et al.[2023]

In a retrospective analysis of 7 patients with prior allogeneic stem cell transplants (alloSCT) who received cilta-cel, an overall response rate of 85.7% was observed, indicating that cilta-cel is effective even in this heavily pretreated group.

The safety profile of cilta-cel in patients with prior alloSCT was similar to that of patients without alloSCT, with manageable side effects like cytokine release syndrome and no reported cases of graft-versus-host disease, suggesting that cilta-cel may be a viable treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. Htut, M., Dhakal, B., Cohen, AD., et al.[2023]

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

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

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

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Developing lisocabtagene maraleucel chimeric antigen receptor T-cell manufacturing for improved process, product quality and consistency across CD19+ hematologic indications. [2022]

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

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. [2023]

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

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. [2023]