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Advanced Solid TumorPhase 1NCT03874897

Chimeric Antigen Receptor T Cells Targeting claudin18.2 in Solid Tumors.

A Phase 1 study testing CAR-CLDN18.2 T-Cells, PD-1 Monoclonal Antibody and Chemotherapy in people with Advanced Solid Tumor, run by Peking University at 3 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

An open label, single/multiple dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-claudin18.2 chimeric antigen receptor T cell in advanced solid tumor. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Advanced Solid Tumor
What is being tested?
CAR-CLDN18.2 T-Cells, PD-1 Monoclonal Antibody and Chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
3 sitesChina
Study dates
26 Mar 2019to 26 Jan 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged 18 to 75 years, male or female;
  • Subjects with pathologically confirmed solid tumors (ie, advanced gastric cancer, esophagogastricgastroesophageal junction cancer, and pancreatic cancer) and have been failed to at least first-one prior line of systemic treatment;
  • Tumor tissue samplessample was positive for claudin 18.2 positive through for claudin18.2 IHC staining;assay(≥2+, and ≥40%);
  • Estimated life expectancy > 12 weeks;
  • According to the RECIST 1.1, there is at least one measurable or unmeasurable tumor lesionslesion；
  • ECOG physical status score 0 ~ 1, within 24 hours prior to apheresis, and at baseline (prior to pre-treatment);
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  • Sufficient venous access for mononuclear cell collection (abbreviation: apheresis)
  • Subjects should have adequate organ functions before screening and pre-treatment (at baseline).
  • Female subjects of childbearing age must undergo a serum pregnancy test at screening and prior to preconditioning and the results must be negative, and are willing to use a very effective and reliable method of contraception within 1 year after the last study treatment. The methods that can be used are: bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusion; or approved oral, injection or hormone-imparting contraceptive methods; or barrier contraceptive method: containing spermicidal foam / Gel/film/cream/suppository condom or occlusive cap (diaphragm or cervix/cap);
  • Men who have actively sexual intercourse with women with child-bearing potential, must agree to use barrier-based contraception if they have no vasectomy, for example, a condom containing a spermicidal foam/gel/film/paste/suppository, or use a contraceptive method for their spouse (see article 9 of the inclusion criteria). Moreover, all men are absolutely forbidden to donate sperm within 1 year after receiving the last study treatment infusion；
  • Subject participates in this clinical trial and sign Informed Consent Form voluntarily.

Who cannot join

  • Pregnant or lactating women;
  • HIV, Treponema pallidum or HCV serologically positive;
  • Any uncontrollable active infection, including but not limited to active tuberculosis, HBV infection (HBsAg positive, or HBcAb positive and HBV DNA positive);
  • Subjects have clinically significant thyroid dysfunction determined by investigator (serum thyroid hormone assays TT4, TT3, FT3, FT4, and serum thyroid stimulating hormone TSH) which is not suitable for entering into the study;
  • The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; except hair loss and, hyperpigmentation or other tolerable events determined by investigator or laboratory abnormalities allowed by the protocol;
  • Subjects who are using steroidshave recieved ≥15 mg/day glucocorticoid systemically currently within 7 days prior to apheresis; those using inhaled steroids recently or currently are not excluded;
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  • Previously allergic to immunotherapy and related drugs, history of severe allergiespreconditioning drug such as cyclophosphamide, fludarabine, or allergiestocilizumab or allergic to components of CT041CAR-CLDN18.2T injection, allergic to β-lactam antibiotics;the CT041 infusion;
  • Previously received any chimeric antigen receptor-modified T-cells(including CAR-T、TCR-T) .
  • Subjects have untreated or symptomatic brain metastases;
  • Subjects have central or extensivelywith centralcor diffused metastases in lung and .extensiveor diffused metastases in liver;liveror with rapid tumor progression since screening period evaluated by the investigator preconditioning (at baseline)；
  • The largest target tumor lesion>4cm
  • Subjects with unstable or active ulcers and gastrointestinal bleeding currently;
  • Subjects with a history of organ transplantation or awaiting organ transplantation;
  • Subjects requiring anticoagulant therapy;
  • Subjects requiring continuous anti-platelet therapy;
  • Subjects who have undergone major surgery or significant trauma within 4 weeks prior to apheresis, or who are expected to undergo major surgery during the study;
  • There are no other serious diseases that may limit subjects' participation in this trial;
  • The investigator assessed that the subject was unable or unwilling to comply with the requirements of the study protocol;
  • Blood oxygen saturation ≤ 95% before pre-treatmentapheresis or preconditioning (accept finger oxygen detection method);
  • Prior to pretreatmentpreconditioning, subjects developed, including but not limited to, new arrhythmias that could not be controlled with drugs, hypotension requiring pressor agent, bacterial, fungal or viral infections that required intravenous antibiotics. Creatinine clearance rate <40mL / min; The investigator judges that the subject is not suitable for continuing the trial. Subjects who use antibiotics to prevent infection can continue the trials if judged by the investigator;
  • The subject has a central nervous system disease sign or an abnormal neurological test result with clinical significance;
  • The subject is currently suffered from or have suffered from other incurable malignant tumors within previous 3 years, except in situ cervical cancer or skin basal cell cancer.

Trial locations and contacts

3 sites in 1 country.

China3 sites

  • Department of GI Oncology, Peking University Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • The First Affiliated Hospital , Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310006

  • The First Affiliated Hospital of Zhengzhou University

    Zhengzhou, Henan, 450052

Other trials in China

About this study

Official title: An Open Label, Single/Multiple Dose Exploratory Clinical Study to Evaluate the Safety, Efficacy, and Cytokinetics of Autologous Humanized Anti-claudin18.2 Chimeric Antigen Receptor T Cell in Advanced Solid Tumor Subjects

An open label, single/multiple dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-claudin18.2 chimeric antigen receptor T cell in advanced solid tumor.

Read the detailed description

This study is an open, single/multiple infusion, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of CAR-CLDN18.2 T cell therapy, and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumor with positive claudin 18.2 expression and failed to standard systemic treatment.

Being tested
CAR-CLDN18.2 T-Cells, PD-1 Monoclonal Antibody, Chemotherapy
Keywords
Advanced solid tumor, claudin18.2, CAR-T cell therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CAR-CLDN18.2 T-CellsDrug

    Also called Chimeric Antigen Receptor T Cells Targeting Claudin18.2

    Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses

    • Chimeric Antigen Receptor T Cells Targeting Claudin18.2

  • PD-1 Monoclonal AntibodyDrug

    Also called Toripalimab

    Chimeric Antigen Receptor T Cells Targeting Claudin18.2 with PD-1

  • ChemotherapyDrug

    First-line systemic therapy according to physician's choice

Study groups in NCT03874897
Study groupRoleWhat they receive
CAR-CLDN18.2 T-CellsExperimentalThe subjects enrolled will be sequentially assigned to the corresponding dose level.
Receives: Drug: CAR-CLDN18.2 T-Cells
Cohort 1ExperimentalCT041 monotherapy in patients with GI cancers who failed standard chemotherapy
Receives: Drug: CAR-CLDN18.2 T-Cells
Cohort 2ExperimentalCT041 plus anti-PD1 therapy in patients with GI cancers who failed standard chemotherapy
Receives: Drug: CAR-CLDN18.2 T-Cells; Drug: PD-1 Monoclonal Antibody
Cohort 3ExperimentalCT041 sequential treatment after first-line therapy in GC/GEJ
Receives: Drug: CAR-CLDN18.2 T-Cells; Drug: Chemotherapy
Cohort 4Experimentalprior treatment failure to anti-CLDN18.2 monoclonal antibody
Receives: Drug: CAR-CLDN18.2 T-Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (DLT)

    Safety

    Measured: 28 days of single infusion

  2. Maximum tolerated dose (MTD)

    tolerability

    Measured: 28 days of single infusion

Secondary outcomes (9)

  1. Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)

    CAR-CLDN18.2 DNA in peripheral blood detected by q-PCR at each visit after infusion

    Measured: 26 weeks

  2. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Adverse events occurring through 26 weeks and 12 months post infusion of CAR-CLDN18.2 T-Cell infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.

    Measured: 1 year

  3. Antitumor efficacy-Progression-free survival (PFS)

    The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.

    Measured: 1 year

  4. Antitumor efficacy-Duration of response (DOR)

    The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause

    Measured: 1 year

  5. Antitumor efficacy-Duration of disease control (DDC)

    The period from the first evaluation of clinical benefit to the first evaluation of PD or any cause of death.

    Measured: 1 year

  6. Antitumor efficacy-Overall survival (OS)

    The period from the first infusion to any cause of death

    Measured: 1 years

  7. Antitumor efficacy-Objective response rate (ORR)

    The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 4 weeks after the first evaluation

    Measured: 1 year

  8. Antitumor efficacy-Disease control rate (DCR)

    The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).

    Measured: 1 year

  9. Long term survival follow up

    The period from the first infusion to any cause of death

    Measured: 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2019
  2. Study start26 Mar 2019
  3. Primary completion20 Mar 2021
  4. Study completion26 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03874897
Sponsor's protocol ID
CT041-CG4006
Status last verified
Apr 2024
First submitted
11 Mar 2019
Last updated
30 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Liu C, Zeng H, Li J, Zhang P, Liu D, Zhang M, Xue R, Gong J, Zhang X, Sun Y, Shen L, Qi C. Long-term control of peritoneal metastases following claudin 18.2-targeted CAR T-Cell therapy in advanced gastric cancer. J Hematol Oncol. 2026 Jul 1;19(1):48. doi: 10.1186/s13045-026-01826-2.

    PubMed 42381043

  • Li J, Liu L, Tao M, Han Z, Ma M, Jiang L, Liu C, Liu D, Zhang P, Zhang M, Xue R, Gong J, Zhang X, Shen L, Qi C. Impact of concomitant medications on efficacy of CLDN18.2-specific CAR-T cell therapy in advanced gastric cancer. Br J Cancer. 2026 Feb;134(3):439-446. doi: 10.1038/s41416-025-03289-7. Epub 2025 Nov 29.

    PubMed 41318814

  • Li J, Tao M, Liu L, Liu C, Ma M, Liu D, Zhang P, Zhang M, Xue R, Gong J, Zhang C, Zhang X, Shen L, Qi C. Peripheral blood neutrophils contribute to Claudin18.2-specific CAR-T cell treatment resistance in advanced gastric cancer. Br J Cancer. 2025 Jun;132(12):1167-1176. doi: 10.1038/s41416-025-03015-3. Epub 2025 Apr 17.

    PubMed 40246985

  • Qi C, Liu C, Gong J, Liu D, Wang X, Zhang P, Qin Y, Ge S, Zhang M, Peng Z, Zhou J, Lu Z, Lu M, Cao Y, Yuan J, Wang Y, Wang Z, Xue R, Peng X, Wang Y, Yuan D, Li J, Zhang X, Shen L. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results. Nat Med. 2024 Aug;30(8):2224-2234. doi: 10.1038/s41591-024-03037-z. Epub 2024 Jun 3.

    PubMed 38830992

  • Qi C, Zhang P, Liu C, Zhang J, Zhou J, Yuan J, Liu D, Zhang M, Gong J, Wang X, Li J, Zhang X, Li N, Peng X, Liu Z, Yuan D, Baffa R, Wang Y, Shen L. Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials. J Clin Oncol. 2024 Jul 20;42(21):2565-2577. doi: 10.1200/JCO.23.02314. Epub 2024 May 24.

    PubMed 38788174

  • Qi C, Xie T, Zhou J, Wang X, Gong J, Zhang X, Li J, Yuan J, Liu C, Shen L. CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer. J Hematol Oncol. 2023 Sep 9;16(1):102. doi: 10.1186/s13045-023-01491-9.

    PubMed 37689733

  • Qi C, Gong J, Li J, Liu D, Qin Y, Ge S, Zhang M, Peng Z, Zhou J, Cao Y, Zhang X, Lu Z, Lu M, Yuan J, Wang Z, Wang Y, Peng X, Gao H, Liu Z, Wang H, Yuan D, Xiao J, Ma H, Wang W, Li Z, Shen L. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat Med. 2022 Jun;28(6):1189-1198. doi: 10.1038/s41591-022-01800-8. Epub 2022 May 9.

    PubMed 35534566

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CAR-CLDN18.2 T-Cells, PD-1 Monoclonal Antibody and Chemotherapy in people with Advanced Solid Tumor, run by Peking University at 3 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (DLT) (time frame: 28 days of single infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03874897, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2024.

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