CAR-T Cell Therapy for Gastrointestinal Cancers

Recruiting at 4 trial locations

Overseen By Jason B Litten, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Chimeric Therapeutics

Must not be taking: Corticosteroids, Antibiotics

Disqualifiers: CNS metastases, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

135 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CHM-2101, which uses the body's own immune cells, known as CAR-T cells, to combat advanced gastrointestinal (GI) cancers. It targets individuals whose cancer has returned or has not responded to at least one previous treatment. Those treated for stomach, colon, or certain types of rectal cancers and who have exhausted standard treatment options might be suitable candidates. Participants will receive a combination of medications before a single dose of CHM-2101. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but ongoing treatment with high-dose corticosteroids is not allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that CHM-2101 is likely to be safe for humans?

Research shows that CHM-2101, a new treatment using CAR T-cell therapy, is in the early stages of testing for human safety. This treatment targets and destroys certain cancer cells in the digestive system. As it is in the first two phases of research, scientists are still assessing its safety and tolerability.

Although detailed safety information isn't yet available, the FDA has granted CHM-2101 fast track status for related cancers, suggesting promising early evidence. This status often indicates potential benefits outweigh risks, but it doesn't guarantee safety.

Early-phase trials primarily ensure a treatment's safety and determine the correct dose. So far, no major safety issues have been publicly reported, but the risks of side effects remain under study. Prospective participants should discuss possible risks with the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for gastrointestinal cancers, which often involve chemotherapy and targeted therapies, CHM-2101 is unique because it utilizes CAR-T cell therapy. This approach involves engineering a patient's own T-cells to specifically recognize and attack cancer cells, providing a highly personalized treatment. Researchers are excited about CHM-2101 because it targets CDH17, a molecule commonly found on the surface of gastrointestinal cancer cells, potentially leading to more effective cancer cell eradication with fewer side effects. Additionally, this therapy offers the promise of long-lasting remission by harnessing the body's immune system.

What evidence suggests that CHM-2101 might be an effective treatment for gastrointestinal cancers?

Research shows that CHM-2101, the investigational treatment in this trial, is designed to find and destroy certain cancer cells in the digestive system. It targets cells that produce a protein called CDH17, which is linked to many digestive system cancers. Early studies suggest that targeting CDH17 could help overcome resistance to several drugs, a common issue in these cancers. The FDA has fast-tracked the treatment, indicating its potential in treating these difficult cancers. Initial results suggest that CHM-2101 might effectively target and kill cancer cells, offering hope for those with advanced digestive system cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Jennifer Eads, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with advanced GI cancers, including neuroendocrine tumors and colorectal or stomach cancer, that didn't respond to at least one standard treatment. Participants must have measurable disease (except in early phase), provide tissue samples, and be physically able to undergo the therapy.

Inclusion Criteria

Left ventricular ejection fraction of at least 50%

Availability of unstained tumor tissue slides from archived tumor tissue or a new tumor biopsy

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

I do not have uncontrolled Crohn's, ulcerative colitis, or similar GI disorders.

Half or more of my liver is affected by cancer.

I am currently on high-dose corticosteroid therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Manufacturing

Eligible participants undergo leukapheresis to collect PBMCs for product manufacturing, including enrichment of T cells, lentiviral transduction, ex vivo expansion, and cryopreservation of the CHM-2101 cell product.

4-6 weeks

Bridging Chemotherapy

Bridging chemotherapy is permitted to maintain disease stability during CHM-2101 manufacturing time, but is prohibited within the 2 weeks prior to leukapheresis and 2 weeks prior to planned CHM-2101 infusion.

Variable

Treatment

Participants receive three daily doses of IV fludarabine and cyclophosphamide, followed by a single dose of IV CHM-2101.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up continuing for 18 months or until disease progression.

18 months

What Are the Treatments Tested in This Trial?

Interventions

• CHM-2101

Trial Overview CHM-2101 CAR-T cell therapy is being tested on patients with specific gastrointestinal cancers. This personalized treatment involves modifying a patient's own immune cells to target and destroy cancer cells.

How Is the Trial Designed?

Group I: Autologous CDH17 CAR T-cell Therapy Experimental Treatment 1 Intervention

After receiving three daily doses of IV fludarabine and cyclophosphamide, participants will receive a single dose of IV CHM-2101. The dose of CHM-2101 during Phase 1 will be based on "3+3" rules of dose escalation. The recommended Phase 2 dose will be based on results from the Phase 1.

Who Is Running the Clinical Trial?

Chimeric Therapeutics

Lead Sponsor

Trials

2

Recruited

180+

Published Research Related to This Trial

A phase I trial of CAR T-cell therapy targeting claudin 18.2, which is mainly found in stomach mucosal cells, demonstrated promising efficacy against advanced digestive system cancers.

The therapy showed acceptable safety, indicating it could be a viable treatment option for patients with solid tumors, which have traditionally been challenging to treat with CAR T-cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric Cancer CAR T-cell Target Antigen ID'd. [2022]

CDH17 CAR-T cells showed strong cytotoxic activity against small cell lung cancer (SCLC) cells in vitro, specifically targeting CDH17-expressing cells while sparing those that do not express this marker, indicating a precise therapeutic approach.

In an SCLC xenograft model, CDH17 CAR-T cells significantly slowed tumor growth without causing noticeable side effects, as evidenced by stable body weight in treated subjects, suggesting a favorable safety profile for this immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CDH17 with Chimeric Antigen Receptor-Redirected T Cells in Small Cell Lung Cancer. Tian, W., Zhao, J., Wang, W.[2023]

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]

B7H3-targeting CAR-T cells demonstrated effective tumor-killing activity against gastric cancer (GC) cells in both laboratory and animal studies, suggesting a promising new treatment approach.

The study found that B7H3 is linked to the stemness of tumor cells, meaning that targeting this protein could also help eliminate cancer stem cells, potentially leading to better treatment outcomes for patients with GC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor responses in gastric cancer by targeting B7H3 via chimeric antigen receptor T cells. Sun, F., Yu, X., Ju, R., et al.[2022]

CDH17 is consistently up-regulated in gastric cancer, and higher levels of this protein are associated with poorer overall survival rates in patients, indicating its potential as a prognostic biomarker.

Targeting CDH17 through RNA interference significantly inhibits gastric cancer cell proliferation and tumor growth in mouse models, suggesting that it could be a promising therapeutic target by disrupting Wnt/β-catenin signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CDH17 suppresses tumor progression in gastric cancer by downregulating Wnt/β-catenin signaling. Qiu, HB., Zhang, LY., Ren, C., et al.[2021]

The 111In-labeled anti-CDH17 monoclonal antibody (Mab) D2101 effectively targets CDH17 in gastric cancer, showing high tumor uptake (39.2% ID/g) and low uptake in normal tissues, indicating its potential as a safe imaging probe.

Immunohistochemical analysis demonstrated that CDH17 is more frequently expressed in gastric cancer specimens compared to HER2, suggesting that CDH17 could serve as a more reliable diagnostic marker for staging gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

111In-labeled anti-cadherin17 antibody D2101 has potential as a noninvasive imaging probe for diagnosing gastric cancer and lymph-node metastasis. Fujiwara, K., Tsuji, AB., Sudo, H., et al.[2020]

A llama-derived nanobody, VHH1, was used to create CDH17-targeted CAR T cells (CDH17CARTs) that effectively killed gastrointestinal cancers and neuroendocrine tumors in mouse models, demonstrating their potential as a new treatment for these solid tumors.

Importantly, CDH17CARTs did not harm normal intestinal cells, suggesting that targeting CDH17 could lead to safer cancer immunotherapies by avoiding damage to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. Feng, Z., He, X., Zhang, X., et al.[2022]

Olfactory receptor OR2H1 is widely expressed in various solid tumors, such as ovarian, lung, and breast cancers, while its expression in normal tissues is limited to the testis, suggesting a potential target for cancer therapy.

CAR T cells engineered to target OR2H1 demonstrated effective cytotoxicity against tumor cells in both laboratory and animal models, indicating that this approach could be a promising treatment for a range of epithelial cancers with a potentially acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory Receptor OR2H1 Is an Effective Target for CAR T Cells in Human Epithelial Tumors. Martin, AL., Anadon, CM., Biswas, S., et al.[2023]

The study developed a chimeric antigen receptor (CAR) targeting c-Met, which is highly expressed in about 20% of gastric cancer patients, showing promising results in both in vitro and in vivo models.

c-Met CAR T cells demonstrated significant tumor growth inhibition in a xenograft model of gastric cancer, indicating their potential as an effective therapy for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer. Kang, CH., Kim, Y., Lee, DY., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS844

A phase 1/2 study to evaluate CHM-2101, an autologous ... CHM CDH17 is a third generation autologous CAR T-cell product candidate that was designed to target and eradicate CDH17+ solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06055439

NCT06055439 | A Phase 1/2 Study to Evaluate CHM-2101, ... The goal of this clinical trial is to evaluate CHM-2101, an autologous CDH17 CAR T-cell therapy for the treatment of advanced gastrointestinal (GI) cancers ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT472336

A phase 1/2 study to evaluate CHM-2101, an autologous ... CHM CDH17 is a third generation autologous CAR T-cell product candidate that was designed to target and eradicate CDH17+ solid tumors.

4. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-chm-cdh17-for-gastroenteropancreatic-nets

FDA Grants Fast Track Designation to CHM CDH17 for ... CHM CDH17 has received fast track designation from the FDA for the treatment of patients with gastroenteropancreatic neuroendocrine tumors.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12281427/

Overcoming multidrug resistance in gastrointestinal ... Cadherin 17 (CDH17) has emerged as a promising target for gastrointestinal (GI) cancers, which are often complicated by multidrug resistance ...