SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor

A Phase Ib/III Study of SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor

This study consists of two research phases:

Phase Ib (includes dose escalation stage and efficacy expansion stage): To explore the safety, tolerability and initial efficacy of SHR-A1904 in the treatment of CLDN18.2-positive advanced solid tumors, and to determine the recommended dose and recommended population for the Phase III combination study.

Phase III: A randomized, Open-Label, multicenter clinical study of SHR-A1904 combined with chemotherapy and immunotherapy Versus chemotherapy combined with immunotherapy for CLDN18.2-positive advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: CLDN18.2-positive Advanced Solid Tumor
• Intervention / Treatment: Drug: SHR-A1904; Adebrelimab; Drug: SHR-A1904; CAPOX; Adebrelimab

• Study Type: Interventional
• Enrollment (Estimated): 924
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Di Zong; Phone Number: 0518-82342973; Email: di.zong@hengrui.com
• Study Contact Backup: Name: Qi Shi; Phone Number: 0518-82342973; Email: qi.shi.qs16@hengrui.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Ruihua Xu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 to 75 years old (including boundary values);
2. Volunteer to participate in this clinical study and sign informed consent;
3. ECOG score 0-1;
4. Expected survival ≥3 months;
5. Pathologically confirmed locally advanced unresectable or metastatic solid tumors;
6. positive CLDN18.2 expression in tumor tissue;
7. There is at least one measurable lesion that meets the RECIST 1.1 criteria;
8. Adequate bone marrow and organ function.

Exclusion Criteria:

1. Plan to receive any other antitumor therapy during this trial; Received other investigational drugs or treatments that are not on the market within 4 weeks prior to the first administration; Anti-tumor therapy, such as chemotherapy, radiotherapy, biotherapy, targeted therapy or immunotherapy, was received within 4 weeks before the first administration of the study drug. Palliative radiotherapy or local therapy within 2 weeks before the first administration of the study drug; Had major surgery other than diagnosis or biopsy within the 4 weeks prior to the first administration or randomization and required elective surgery during the trial.
2. HER2 expression in tumor tissue is positive.
3. The adverse reactions of previous anti-tumor therapy has not recovered to NCI-CTCAE v5.0 grade≤ 1.
4. Has ≥ grade 2 peripheral sensory neuropathy.
5. Has an allergic reaction to any of the components treated in this study, or are allergic to humanized monoclonal antibody products.
6. Has a history or current history of meningeal metastasis; or active brain metastases.
7. Presence of dysphagia or other factors affecting the use of oral medications.
8. Additional malignancy within the five years prior to the first administration or randomization.
9. Has an active autoimmune disease or a history of autoimmune disease.
10. Received systemic use of corticosteroids or other immunosuppressants for immunosuppressive effects within 14 days prior to the first administration or randomization.
11. Has a history of clinically significant lung disease.
12. Has serosal effusion ≥ grade 3 (based on NCI CTCAE5.0 criteria).
13. There was an active infection requiring systemic treatment within 2 weeks prior to the first administration or randomization.
14. A history of immunodeficiency, including a positive HIV test; Presence of active hepatitis B or hepatitis C.
15. People who have previously received allogeneic hematopoietic stem cell transplantation or organ transplantation.
16. Has severe cardiovascular and cerebrovascular diseases.
17. Gastrointestinal perforation and/or gastrointestinal fistula within the last 6 months prior to the first administration or randomization; Active gastrointestinal bleeding occurred 3 months before the first administration or randomization.
18. In the investigator's judgment, the subject has other factors that could have affected the study results or led to the forced termination of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1904 combined with Adebrelimab; SHR-A1904+ Adebrelimab	Drug: SHR-A1904; Adebrelimab; SHR-A1904 combined with Adebrelimab: SHR-A1904+ Adebrelimab
Experimental: SHR-A1904 combined with CAPOX and Adebrelimab; SHR-A1904+ CAPOX+ Adebrelimab	Drug: SHR-A1904; CAPOX; Adebrelimab; SHR-A1904 combined with Adebrelimab and CAPOX (Capecitabine, Oxaliplatin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of AE	Phase 1b	Up to follow-up period, approximately 24 months
Dose Limiting Toxicity (DLT)	Phase 1b	approximately 24 months
Maximal Tolerable Dose (MTD)	Phase 1b	approximately 24 months
Phase III Recommended Dose (RP3D)	Phase 1b	approximately 24 months
Progression-free survival (PFS) assessed by blind Independent Center Review (BICR) based on RECIST 1.1 criteria	Phase 3	approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SHR-A1904 toxin binding antibody	Phase 1b	approximately 24 months
SHR-A1904 Total antibody	Phase 1b	approximately 24 months
Immunogenicity indicators of SHR-A1904: drug resistant antibody (ADA) and neutralizing antibody (NAb)	Phase 1b	approximately 24 months
Expression level of CLDN18.2 in tumor tissues	Phase 1b	approximately 24 months
Overall survival (OS)	Phase 3	approximately 36 months
Incidence and severity of AE	Phase 3	approximately 36 months

Collaborators and Investigators

• Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: April 1, 2024
• First Submitted That Met QC Criteria: April 1, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SHR-A1904-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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