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

This is a FTiH, Phase 1 IIT to evaluate the safety, feasibility, cellular kinetics (CK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of AZD6422 in adult participants with advanced or metastatic CLDN18.2+ GI tumors.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Tumors
• Intervention / Treatment: Biological: AZD6422 CLDN18.2 CAR-T product

Detailed Description

Qualified researchers can request access to anonymized individual patient-level data from sponsor or the collaborator group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the sponsor disclosure commitment. Yes, indicates that sponsors are accepting requests for IPD, but this does not mean all requests will be shared.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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)

Number of Arms

1

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)	Biological: AZD6422 CLDN18.2 CAR-T product; AZD6422 CAR-T product infusion after pre-conditioning; Other Names: AZD6422

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent AEs, AESIs, and SAEs.	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.	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.	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	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	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	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 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: Peking University
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Lin Shen, PhD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Actual): June 25, 2025
• Study Completion (Actual): June 25, 2025

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 1, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: CLDN18.2+ GI Tumors Solid tumor CAR-T Cell therapy AZD6422
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: D9540C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from sponsor or the collaborator group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the sponsor disclosure commitment. Yes, indicates that sponsors are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: Sponsor or the collaborator group of companies will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to disclosure commitment.
• IPD Sharing Access Criteria: When a request has been approved sponsor will provide access to the de-identified individual patient-level detain an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No