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

Phase 1

Recruiting

• Conditions: Cldn18.2-positive Advanced Solid Tumor
• Interventions: Drug: SHR-A1904; Adebrelimab; Drug: SHR-A1904; CAPOX; Adebrelimab

• Registration Number: NCT06350006
• Lead Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

Brief Summary

This study consists of two research phases:

Phase Ib (includes dose escalation phase and efficacy extension phase): 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, double-blind, multicenter clinical study of SHR-1904 combined with chemotherapy and immunotherapy Versus chemotherapy combined with immunotherapy for CLDN18.2-positive advanced solid tumors.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-01
• Study First Submitted QC: 2024-04-01
• Study First Posted: 2024-04-05
• Study Start: 2024-05-29
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-08
• Last Update Posted: 2024-08-09
• Primary Completion: 2027-12-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 924

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. Stage III: 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 subjects has other factors that could have affected the study results or led to the forced termination of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SHR-A1904 combined with Adebrelimab	SHR-A1904; Adebrelimab	SHR-A1904+ Adebrelimab
SHR-A1904 combined with CAPOX and Adebrelimab	SHR-A1904; CAPOX; Adebrelimab	SHR-A1904+ CAPOX+ Adebrelimab

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China