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

NCT06350006 | Recruiting Phase 1

• 1 other identifier: SHR-A1904-301
• Study Type: interventional
• Target: 924
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CLDN18.2-positive Advanced Solid Tumor

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• SHR-A1904 toxin binding antibody

  approximately 24 months

• SHR-A1904 Total antibody

  approximately 24 months

• Immunogenicity indicators of SHR-A1904: drug resistant antibody (ADA) and neutralizing antibody (NAb)

  approximately 24 months

• Expression level of CLDN18.2 in tumor tissues

  approximately 24 months

• Overall survival (OS)

  approximately 36 months

Study Arms (2)

SHR-A1904 combined with Adebrelimab

EXPERIMENTAL

SHR-A1904+ Adebrelimab

Drug: SHR-A1904; Adebrelimab

SHR-A1904 combined with CAPOX and Adebrelimab

EXPERIMENTAL

SHR-A1904+ CAPOX+ Adebrelimab

Drug: SHR-A1904; CAPOX; Adebrelimab

Interventions

SHR-A1904; Adebrelimab DRUG

SHR-A1904 combined with Adebrelimab: SHR-A1904+ Adebrelimab

SHR-A1904 combined with Adebrelimab

SHR-A1904; CAPOX; Adebrelimab DRUG

SHR-A1904 combined with Adebrelimab and CAPOX (Capecitabine, Oxaliplatin)

SHR-A1904 combined with CAPOX and Adebrelimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• HER2 expression in tumor tissue is positive.
• The adverse reactions of previous anti-tumor therapy has not recovered to NCI-CTCAE v5.0 grade≤ 1.
• Has ≥ grade 2 peripheral sensory neuropathy.
• Has an allergic reaction to any of the components treated in this study, or are allergic to humanized monoclonal antibody products.
• Has a history or current history of meningeal metastasis; or active brain metastases.
• Presence of dysphagia or other factors affecting the use of oral medications.
• Additional malignancy within the five years prior to the first administration or randomization.
• Has an active autoimmune disease or a history of autoimmune disease.
• Received systemic use of corticosteroids or other immunosuppressants for immunosuppressive effects within 14 days prior to the first administration or randomization.
• Has a history of clinically significant lung disease.
• Has serosal effusion ≥ grade 3 (based on NCI CTCAE5.0 criteria).
• There was an active infection requiring systemic treatment within 2 weeks prior to the first administration or randomization.
• A history of immunodeficiency, including a positive HIV test; Presence of active hepatitis B or hepatitis C.
• People who have previously received allogeneic hematopoietic stem cell transplantation or organ transplantation.

Sponsors & Collaborators

• Shanghai Hengrui Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Central Study Contacts

Qi Shi

CONTACT

0518-82342973; qi.shi.qs16@hengrui.com

Di Zong

CONTACT

0518-82342973; di.zong@hengrui.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is a multicenter Phase Ib/III clinical study. Phase Ib consists of two stages, IB-A for dose escalation and IB-B for efficacy expansion. The Phase III multi-center, randomized ,active-controlled, Open-label study was designed to evaluate the efficacy and safety of SHR-A1904 combined chemotherapy and immunotherapy versus chemotherapy combined immunotherapy in first-line treatment of CLDN18.2-positive solid tumors patients.

Study Record Dates

• First Submitted: April 1, 2024
• First Posted: April 5, 2024
• Study Start: May 29, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: December 31, 2025

Record last verified: 2025-09

Locations

CN (1)