Testing AZD6422 for advanced gastrointestinal tumors with CLDN18.2 expression
FTiH, Phase 1 Investigator-Initiated Trial (IIT) to Evaluate the Safety, Feasibility, Cellular Kinetics, and Preliminary Antitumor Activity of AZD6422 in Adult Participants With Advanced or Metastatic CLDN18.2+ GI Tumors
This study is testing a new CAR-T cell therapy called AZD6422 to see if it can help adults with advanced gastrointestinal tumors that haven't responded to other treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 96 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Peking University Academic / other |
| Drugs / interventions | CAR-T |
| Locations | 1 site (Beijing) |
| Trial ID | NCT05981235 on ClinicalTrials.gov |
What this trial studies
This Phase 1 trial evaluates the safety and effectiveness of AZD6422, a CAR-T cell therapy targeting CLDN18.2, in adults with advanced or metastatic gastrointestinal tumors. The study focuses on assessing cellular kinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity. Participants must have a confirmed diagnosis of unresectable or metastatic GI adenocarcinoma that has not responded to previous treatments. The trial aims to gather critical data on the therapy's feasibility and potential benefits for patients.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with advanced CLDN18.2+ gastrointestinal tumors who have failed prior treatments.
Not a fit: Patients who have previously received CAR-T cell therapy or have a history of upper digestive tract bleeding related to CLDN18.2 targeting may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat gastrointestinal tumors.
How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this specific approach targeting CLDN18.2 in gastrointestinal tumors is relatively novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 1Capable of giving signed informed consent and keep compliance with the requirements and restrictions listed in the ICF and in this protocol. 2Age ≥ 18 years at the time of signing the informed consent. 3At least 1 lesion, that qualifies as a RECIST v1.1 target lesion at baseline. Histologically confirmed diagnosis of unresectable or metastatic GI adenocarcinoma that has failed prior lines systemic treatment or with standard anticancer therapy. 4Confirmation of CLDN18.2 expression determined by IHC . 5ECOG PS of 0 to 1. 6 Life expectancy of \> 12 weeks. 7Evidence of appropriate organ function, as determined by clinical laboratory values. 8Participants of childbearing potential (including woman of childbearing potential and males who have a partner) must take highly effective contraception measure. Exclusion Criteria: * 1.Prior treatment with any CAR-T cell therapy. 2.History of upper digestive tract bleeding secondary to previous CLDN18.2-targeting therapies; clinically significant unstable or active peptic ulcer disease or upper digestive tract bleeding 3.Cancer-related spinal cord compression, leptomeningeal disease, or brain metastases. 4.Receipt of the last dose of anticancer therapy within 5 half-lives or ≤ 21 days prior to apheresis, treatment radiotherapy within 6 weeks (loco-regional palliative radiotherapy within 7 days) prior to apheresis. 5.Treatment with any anticoagulant or antiplatelet therapy. 6.History of, or active, bleeding diatheses. 7.Active or chronic infection disease (s). 8.History of another primary malignancy ≤ 3 years before enrolment. 9.Any history of autoimmune neurological conditions. 10.Other active autoimmune or inflammatory disorders. 11.Stroke, intracranial haemorrhage, or seizure within 6 months of apheresis. 12.Active uncontrolled epilepsy. 13.Cardiac disease, including arrhythmias, QT prolongation, cardiomyopathy and unstable ischaemic heart disease. 14.Uncontrolled intercurrent illness. 15.Steroids or other immunomodulators of systemic therapeutic dose within 14 days prior to apheresis. 16.Prior pegylated G-CSF within 60 days before apheresis. Prior G-CSF/granulocyte-macrophage colony stimulating factor (GM-CSF) within 14 days before apheresis. 17.Any prohibited medication. 18.Major surgery within 2 weeks prior to apheresis, or planned surgery within 4 weeks after study intervention. 19.Any history of life-threatening allergies, hypersensitivity, or severe infusion reaction to monoclonal antibodies or biological therapies, or intolerance to the CAR-T product or its excipients. 20.Toxicity from previous anticancer therapy that has not resolved to baseline levels or to ≤ Grade 1 prior to apheresis. 21.Female participants who are pregnant or breastfeeding or expect to be pregnant or breastfeeding during the study. 22.Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 23.Receipt of live or live attenuated vaccine within 30 days prior to the start of lymphodepletion. 24.Participant has any medical or psychiatric condition.
Where this trial is running
Beijing
- Beijing Cancer Hospital — Beijing, China (Recruiting)
Study contacts
- Principal investigator: Lin Shen, PHD — Peking University Cancer Hospital & Institute
- Study coordinator: Lin Shen, PHD
- Email: linshenpku@163.com
- Phone: 01088196090
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.