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Gastric CancerPhase 1/2NCT04404595

Claudin18.2 CAR-T (CT041) in Patients With Gastric, Pancreatic Cancer, or Other Specified Digestive Cancers

A Phase 1/2 study testing CT041 in people with Gastric Cancer and Pancreatic Cancer, run by CARsgen Therapeutics Co., Ltd. at 16 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages 18 to 76 years
Conditions the study is for
Gastric Cancer, Pancreatic Cancer
What is being tested?
CT041
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
110 participants
Where
16 sitesin 2 countries
Study dates
23 Oct 2020to 1 Sep 2035
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 76 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients are eligible for screening for potential inclusion in the study ( indicates inclusion criteria at Baseline (for subjects to be eligible for preconditioning)):
  • Voluntarily signed the ICF;
  • Age ≥ 18 and < 76 years with pathologically/histologically confirmed diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, referred to collectively as STAD, or pancreatic adenocarcinoma (PAAD);or biliary tract cancers (BTCs, including intrahepatic/extrahepatic cholangiocarcinoma and gallbladder cancer but not ampullary carcinoma);
  • Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay;
  • Estimated life expectancy > 4 months*;
  • Failed or been intolerant of prior lines of systemic therapy:
Show all 53Show fewer
  • For screening:
  • Leukapheresis can be performed for subjects with STAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
  • Leukapheresis can be performed for subjects with PAAD who are receiving first-line treatment, or,
  • Leukapheresis can be performed for subjects with BTC who are receiving first-line treatment.
  • Baseline*:
  • Subjects with STAD who have progressed or were intolerant of at least 2 prior lines of systemic therapy, or,
  • Subjects with PAAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
  • Subjects with BTC who have progressed or were intolerant of at least 1 prior line of systemic therapy. For subjects with CCA with who has FGFR2 fusions or rearrangements, or IDH1-mutant must have received FDA-approved target therapies.
  • At least 1 measurable lesion per RECIST 1.1*;
  • ECOG performance status of 0 or 1*;
  • Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
  • Patients should have adequate CBC counts, renal and hepatic functions*;
  • Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception*;
  • Men must be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion*;
  • Sufficient nutritional status.
  • Exclusion Criteria for screening ( indicates exclusion criteria for baseline as well):
  • Pregnant or lactating women*;
  • HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV), or active syphilis infection;
  • Any active infection requiring systemic treatment*;
  • AEs from previous treatment that have not recovered*;
  • Patients who have clinically significant thyroid dysfunction;
  • Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell;
  • Patients who have received:
  • prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) within one year.
  • organ transplantation.
  • previous anti-claudin18.2 CAR T-cell therapy, mRNA-based cancer immunotherapy, or bispecific T cell engager.
  • Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
  • Patients with heavy tumor burdens;
  • Unstable/active ulcer, anastomotic recurrence with full-thickness tumor infiltration or tumor involving any major vessels, digestive tract bleeding, or recent digestive surgery that may have increased risk of bleeding*;
  • Patients who have a history of esophageal or gastric resection plus current evidence of locally recurrent tumor that involves any major blood vessels or that has evidence of recent bleeding or perforation*;
  • Patients requiring anticoagulant therapy such as warfarin or heparin;
  • Patients requiring long-term antiplatelet therapy;
  • Use of prednisone >/= 10mg daily or other equivalent steroids within 14 days before leukapheresis or preconditioning*;
  • Anticancer treatment within approximately 2 weeks prior to leukapheresis or preconditioning*;
  • Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning*;
  • Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients*;
  • Inadequate pulmonary function*;
  • Patients known to have active autoimmune diseases;
  • Patients with second malignancies;
  • Patients have significant neurologic disorders;
  • Patients are unable or unwilling to comply with the requirements of clinical trial.
  • Additional exclusion criteria solely for baseline (prior to conditioning regimen):
  • Fever > 38.0°C;
  • Active illness or existing toxicity that would place the subject at undue risk;
  • Abrupt deterioration of clinical status or condition;
  • Subjects who have received a live attenuated vaccine 4 weeks before preconditioning.
  • Inclusion Criteria Before Infusion: There are no inclusion criteria at this timepoint.

Who cannot join

  • Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
  • Inadequate pulmonary function;
  • Active infection requiring systemic therapy or causing fever within 7 days prior to investigational infusion;
  • Active illness or toxicity that would place the subject at undue risk;
  • Abrupt deterioration of clinical status or condition;
  • New or worsening Grade ≥ 3 non-hematologic toxicities.

Trial locations and contacts

16 sites in 2 countries.

16 sites in 2 countries

United States15 sites

  • Ohio State University

    Columbus, Ohio, 43210

  • TX Oncology-Baylor Charles Sammons Cancer Center

    Dallas, Texas, 75246

  • Karmanos Cancer Center

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Southern California

    Los Angeles, California, 90089

  • Froedtert Hospital and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Northwell Cancer Institute

    New Hyde Park, New York, 11042

  • The Mount Sinai Hospital

    New York, New York, 10029

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Cancer Hospital

    Rochester, Minnesota, 55905

  • UCSD

    San Diego, California, 92093

  • UCSF

    San Francisco, California, 94143

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Canada1 site

  • Princess Margaret Hospital

    Toronto, Ontario, M5GH 2C1

Other trials in Canada

About this study

Official title: Open-label, Multicenter, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous Anti-claudin 18.2 Chimeric Antigen Receptor T-cell Therapy in Subjects With Advanced Gastric, Pancreatic, or Other Specified Digestive System Cancers

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

Read the detailed description

This is an open label, multi-center, Phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous claudin18.2 chimeric antigen receptor T-cell therapy in patients with advanced gastric, pancreatic or other specified digestive system cancers.

Following consent, patients must have tumor tissue evaluated by CLDN18.2 IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (CT041). Following manufacture of the drug product, subjects will receive preconditioning prior to CT041 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.

Being tested
CT041
Keywords
CAR-T
Medical subject headings
Stomach Neoplasms, Pancreatic Neoplasms

What participants receive

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

  • CT041Biological

    treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion

Study groups in NCT04404595
Study groupRoleWhat they receive
anti-claudin18.2 chimeric antigen receptor T-cell therapyExperimentalPhase 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.
Receives: Biological: CT041

What is being measured

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

  1. Phase 1b (Cohort A): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with specified advanced digestive system cancers (STAD, PAAD, or BTC).

    Incidence of adverse events (AEs), AEs of special interest (cytokine release syndrome [CRS], neurotoxicity, secondary malignancy), serious adverse events (SAEs).

    Measured: up to year 15

  2. Phase 1b (Cohort A): Identify the recommended Phase 2 dose (RP2D) of CT041 therapy in subjects with advanced STAD, PAAD, or BTC.

    Incidence of dose-limiting toxicities (DLTs)

    Measured: day 0 - day 28

  3. Phase 1b (Cohort A): Identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) of CT041 therapy in subjects with STAD, PAAD, or BTC.

    The highest dose below the dose where the escalation was stopped when the frequency or severity of DLTs exceeds predefined safety criteria.

    Measured: day 0 - day 28

  4. Phase 1b (Cohort B): Determine the efficacy of CT041 by ORR in subjects with advanced STAD, PAAD, or BTC.

    Objective response rate by IRC assessment (RECIST v1.1)

    Measured: up to year 15

  5. Phase 2 (Cohort C): Determine the efficacy of CT041 by ORR in subjects with advanced STAD treated at the RP2D.

    Objective response rate by IRC assessment (RECIST v1.1)

    Measured: up to year 15

Secondary outcomes (20)

  1. Phase 1b/2: Objective Response Rate (ORR) per investigator assessment

    Rate of subjects experiencing an objective response (a binary variable indicating whether each subject experienced a ≥ partial response [PR] by Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1]), as determined by investigator assessment.

    Measured: up to year 15

  2. Phase 1b (Cohort A): Duration of Response

    Duration of time from first response to progression of disease as determined by investigator

    Measured: up to year 15

  3. Phase 1b (Cohort A): Time to Progression

    Duration of time in months from the date of CT041 infusion until disease progression, excluding deaths as determined by investigator.

    Measured: up to year 15

  4. Phase 1b (Cohort A): Disease Control Rate

    The incidence of a BOR of CR, PR, or SD based on investigator assessments using RECIST 1.1 criteria.

    Measured: up to year 15

  5. Phase 1b (Cohort A): Progression free survival

    The time in months from the date of CT041 infusion to the earliest date of disease progression or death due to any cause as determined by investigator.

    Measured: up to year 15

  6. Phase 1b (Cohort B): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with specified advanced digestive system cancers (STAD, PAAD, or BTC).

    Incidence of adverse events (AEs), AEs of special interest (cytokine release syndrome [CRS], neurotoxicity, secondary malignancy), serious adverse events (SAEs).

    Measured: up to year 15

  7. Phase 2 (Cohort C): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with advanced STAD.

    Incidence of adverse events (AEs), AEs of special interest (cytokine release syndrome [CRS], neurotoxicity, secondary malignancy), serious adverse events (SAEs).

    Measured: up to year 15

  8. Phase 1b(Cohort B)/2: Duration of Response

    Duration of time from first response to progression of disease as determined by investigator and IRC assessment.

    Measured: up to year 15

  9. Phase 1b(Cohort B)/2: Time to Progression

    Duration of time in months from the date of CT041 infusion until disease progression, excluding deaths as determined by investigator and IRC assessment.

    Measured: up to year 15

  10. Phase 1b(Cohort B)/2: Disease Control Rate

    The incidence of a BOR of CR, PR, or SD based on investigator and IRC assessments using RECIST 1.1 criteria.

    Measured: up to year 15

  11. Phase 1b(Cohort B)/2: Progression free survival

    The time in months from the date of CT041 infusion to the earlier date of disease progression or death due to any cause as determined by investigator and IRC assessment.

    Measured: up to year 15

  12. Phase 1b/2: Overall survival

    The time in months from the date of CT041 infusion until the date of death by any cause.

    Measured: up to year 15

  13. Phase 1b/2: Utilization of Hospital Resources

    Total days of hospitalization, including ICU days, during \& after CT041 infusion as described below:

    • Infusion-related hospital re-admission within 3 months after infusion.
    • The number and percentages of subjects, and the number of hospitalizations due to non-infusion reasons.
    • All-cause re-admission within 3 months after infusion, and from infusion to data cutoff date among those who required rehospitalization
    • Duration of hospitalization in intensive care

    Measured: Day 0 to 3 months

  14. Phase 1b(Cohort B)/2: PK and bio-distribution of CT041

    CAR transgene copy number, peak value, AUC, in vivo persistence.

    Measured: Baseline - month 18

  15. Phase 1b(Cohort B)/2: Health-related Quality of Life (HRQoL) in STAD patients (Cohorts B & C)

    • Change from baseline in HRQoL as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30.
    • Change from baseline in HRQoL as measured by EORTC QLQ-OG25.

    Measured: Baseline - month 18

  16. Phase 1b(Cohort B)/2: CLDN18.2 ICH Assay Performance

    • Association of CLDN18.2 expression level versus tumor response
    • Association of CLDN18.2 expression versus clinical disease characteristics

    Measured: Baseline - month 18

  17. Phase 1b(Cohort B)/2: Cytokine expression level in blood after CT041 infusion

    Evaluate cytokine expression level in blood after CT041 infusion.

    Measured: Baseline - week 20

  18. Phase 1b (Cohort B)/2: Anti-CT041 drug antibodies

    Number of subjects with anti-CT041 drug antibodies

    Measured: Baseline - month 12

  19. Phase 1b (Cohort B)/2: CT041 product characteristics

    Association of CT041 product characteristics with clinical safety/efficacy/PK

    Measured: Baseline - month 18

  20. Phase 1b (Cohort B)/2: Concordance analysis

    Concordance analysis of ORR of IRC assessment vs investigator assessment.

    Measured: up to year 15

Timeline

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

  1. First posted27 May 2020
  2. Study start23 Oct 2020
  3. Primary completion1 Jun 2025 (estimated)
  4. Study completion1 Sep 2035 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
3+3 dose escalation and expansion
Masking
None (open label)
Enrolment
110 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04404595
Sponsor's protocol ID
CT041-ST-02
Status last verified
Jan 2025
First submitted
19 May 2020
Last updated
8 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Botta GP, Chao J, Ma H, Hahn M, Sierra G, Jia J, Hendrix AY, Nolte Fong JV, Ween A, Vu P, Miller A, Choi M, Heyman B, Daniels GA, Kaufman D, Jamieson C, Li Z, Cohen E. Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells. J Immunother Cancer. 2024 Feb 5;12(2):e007927. doi: 10.1136/jitc-2023-007927.

    PubMed 38316518

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CT041 in people with Gastric Cancer and Pancreatic Cancer, run by CARsgen Therapeutics Co., Ltd. at 16 sites in 2 countries.

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 53 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Canada. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Phase 1b (Cohort A): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with specified advanced digestive system cancers (STAD, PAAD, or BTC). (time frame: up to year 15). The study lists 5 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 NCT04404595, which also lists 1 linked publication.

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 8 Jan 2025.

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