Phase 1 Trial of AZD6422 in CLDN18.2+ GI Tumors
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Beijing, China
- Peking University Cancer Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: AZD6422
It is anti-CLDN18.2
CAR-T cell therapy and the study consists of two parts: dose escalation (part 1) and dose expansion (part 2)
|
AZD6422 CAR-T product infusion after pre-conditioning
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of treatment-emergent AEs, AESIs, and SAEs.
Time Frame: Within 24 months of the last AZD6422 infusion or the start of a new anticancer treatment
|
Incidence of treatment-emergent AEs, AESIs, and SAEs.
|
Within 24 months of the last AZD6422 infusion or the start of a new anticancer treatment
|
|
Occurrence of Dose limiting toxicity.
Time Frame: Within 28 days after the first infusion
|
Occurrence of DLTs (Dose limiting toxicity).
|
Within 28 days after the first infusion
|
|
Changes from baseline in vital signs, laboratory parameters, physical examination, and 12-lead ECG.
Time Frame: Within 28 days after the first infusion
|
Changes from baseline in vital signs, laboratory parameters, physical examination, and 12-lead ECG.
|
Within 28 days after the first infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
ORR
Time Frame: 24 months post AZD6422 infusion
|
The proportion of participants who have a confirmed CR or confirmed PR as determined by the investigator at local site per RECIST v1.1.
|
24 months post AZD6422 infusion
|
|
DoR
Time Frame: 24 months post AZD6422 infusion
|
The time from first documented confirmed response until date of documented progression of disease per RECIST v1.1 as determined by investigator at local site or death due to any cause.
|
24 months post AZD6422 infusion
|
|
DCR
Time Frame: 24 months post AZD6422 infusion
|
The proportion of participants who have a confirmed CR, confirmed PR, or who have SD per RECIST v1.1 as assessed by the investigator at local site and derived from the raw tumor data for at least 11 weeks after infusion date.
|
24 months post AZD6422 infusion
|
|
PFS
Time Frame: 24 months post AZD6422 infusion
|
Time from infusion date until progression per RECIST v1.1 as assessed by the investigator at local site, or death due to any cause.
|
24 months post AZD6422 infusion
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Lin Shen, PHD, Peking University Cancer Hospital & Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D9540C00001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.