CLDN18.2-positive Advanced Solid Tumor
Conditions
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.
Interventions
DRUGSHR-A1904; Adebrelimab
SHR-A1904 combined with Adebrelimab: SHR-A1904+ Adebrelimab
DRUGSHR-A1904; CAPOX; Adebrelimab
SHR-A1904 combined with Adebrelimab and CAPOX (Capecitabine, Oxaliplatin)
Sponsors
Shanghai Hengrui Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of AE | Up to follow-up period, approximately 24 months | Phase 1b |
| Dose Limiting Toxicity (DLT) | approximately 24 months | Phase 1b |
| Maximal Tolerable Dose (MTD) | approximately 24 months | Phase 1b |
| Phase III Recommended Dose (RP3D) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SHR-A1904 toxin binding antibody | approximately 24 months | Phase 1b |
| Incidence and severity of AE | approximately 36 months | Phase 3 |
| 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 |
| Expression level of CLDN18.2 in tumor tissues | approximately 24 months | Phase 1b |
| Overall survival (OS) | approximately 36 months | Phase 3 |
Countries
China
Contacts
Primary ContactQi Shi
Backup ContactDi Zong
Outcome results
None listed