CAR T-cell Therapy for Stomach & Pancreatic Cancer

Recruiting at 7 trial locations

Overseen By Legend Biotech USA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Legend Biotech USA Inc

Must not be taking: Anticoagulants, Antiplatelets, Immunosuppressants

Disqualifiers: Cellular immunotherapy, Brain metastasis, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LB1908, a type of CAR T-cell therapy, for individuals with advanced stomach or pancreatic cancer. The goal is to determine if this treatment can help when other standard treatments are no longer effective or suitable. Suitable candidates have a confirmed diagnosis of advanced gastric, gastroesophageal, esophageal, or pancreatic cancer that cannot be treated with surgery and have already tried standard therapies. 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.

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.

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

Research has shown that the treatment LB1908, which targets a protein called Claudin 18.2, has been studied in patients with advanced gastrointestinal cancers. This treatment resembles another therapy called satricabtagene autoleucel, or "satri-cel." Studies on satri-cel indicate it can improve patient outcomes and has a generally manageable safety profile, meaning most side effects are not severe and can be controlled.

Although this trial is in its early stages, the fact that a similar treatment has been tested and found to be generally well-tolerated offers some hope for LB1908's safety in humans. However, since this is a Phase 1 study, the main focus is on ensuring the treatment's safety. Researchers are still learning about how people respond to the treatment. So far, the data appears promising but is still being collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for stomach and pancreatic cancer, like chemotherapy and radiation, work by attacking rapidly dividing cancer cells. But LB1908 works differently, targeting a specific protein called Claudin 18.2 found on cancer cells. Researchers are excited about LB1908 because it uses Chimeric Antigen Receptor (CAR) T-cell therapy to directly harness the body's immune system to fight the cancer, potentially offering a more precise and powerful attack on the tumor with fewer side effects than traditional treatments. This innovative approach could pave the way for more personalized and effective cancer therapies.

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

Research has shown that a new treatment, Claudin 18.2-targeted CAR T-cell therapy, specifically LB1908, could help treat advanced stomach and pancreatic cancers. In earlier studies, patients with stomach and gastroesophageal junction cancers lived longer without their cancer worsening. For pancreatic cancer, the therapy extended the period patients remained cancer-free and reduced cancer markers in their blood. These results suggest that targeting Claudin 18.2 might effectively treat these challenging cancers. The treatment's side effects are considered manageable, which is encouraging for those considering joining the trial. Participants in this trial will receive the experimental LB1908 therapy. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• LB1908

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.

How Is the Trial Designed?

Group I: Experimental LB1908 Experimental Treatment 1 Intervention

Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells

LB1908 is already approved in China, United States for the following indications:

Approved in China as Satricabtagene autoleucel for:

• Gastric adenocarcinoma
• Gastroesophageal junction adenocarcinoma

Approved in United States as Satricabtagene autoleucel for:

• Advanced gastric adenocarcinoma
• Pancreatic adenocarcinoma

Who Is Running the Clinical Trial?

Legend Biotech USA Inc

Lead Sponsor

Trials

3

Recruited

150+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

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

Final results of CT041-CG4006 phase 1 trial. Results: From 26 March 2019 to 26 January 2024, a total of 98 pts received CT041 infusion, including GC (n=73), pancreatic cancer (n=10), ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40460847/

Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) ... These results support satri-cel as a new third-line treatment for advanced gastric or gastro-oesophageal junction cancer patients. Funding: ...

3. carsgen.com carsgen.com/en/news/20251020/

Newsroom | CARsgen In this trial, the sustained disease-free survival and marked declines in CA19-9 levels suggest that satri-cel, an innovative cellular ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00860-8/abstract

Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) ... Satri-cel treatment resulted in a significant improvement in progression-free survival, with a manageable safety profile. These results support ...

5. oncologypipeline.com oncologypipeline.com/apexonco/solid-tumour-car-t-first

A solid tumour Car-T first? | ApexOnco Carsgen Therapeutics' satricabtagene autoleucel, a low-key project that targets Claudin18.2 and secured buy-in from Moderna two years ago, ...

6. carsgen.com carsgen.com/en/news/20250626/

CARsgen Therapeutics Announces NDA Acceptance of ... The National Medical Products Administration (NMPA) of China has accepted the New Drug Application (NDA) for satricabtagene autoleucel (“satri-cel”, CT041)

7. dailynews.ascopubs.org dailynews.ascopubs.org/do/satricabtagene-autoleucel-yields-pfs-and-os-benefit-advanced-gastric-and

Satricabtagene Autoleucel Yields PFS and OS Benefit in ... Satricabtagene autoleucel (satri-cel) significantly improves progression-free survival (PFS) and overall survival (OS) compared with treatment of physician's ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38830992/

Claudin18.2-specific CAR T cells in gastrointestinal cancers Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625008608

Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) ... Satri-cel treatment resulted in a significant improvement in progression-free survival, with a manageable safety profile.