Clinical trial NCT06350006: SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor
Official title: A Phase Ib/III Study of SHR-A1904 Combinations in CLDN18.2-Positive Advanced Solid Tumor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cldn18.2-positive Advanced Solid Tumor
Lead sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-04-05
Enrollment: 924
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a multicenter Phase Ib/III clinical study. Phase Ib consists of two phases, IB-A for dose escalation and IB-B for efficacy extension. The Phase III multi-center, randomized controlled, double-blind 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and severity of AE
timeFrame: Up to follow-up period, approximately 24 months
measure: Dose Limiting Toxicity (DLT)
timeFrame: approximately 24 months
measure: Maximal Tolerable Dose (MTD)
timeFrame: approximately 24 months
measure: Phase III Recommended Dose (RP3D)
timeFrame: approximately 24 months
measure: Progression-free survival (PFS) assessed by blind Independent Center Review (BICR) based on RECIST 1.1 criteria
timeFrame: approximately 36 months
Secondary outcomes:
measure: SHR-A1904 toxin binding antibody
timeFrame: approximately 24 months
measure: SHR-A1904 Total antibody
timeFrame: approximately 24 months
measure: Immunogenicity indicators of SHR-A1904: drug resistant antibody (ADA) and neutralizing antibody (NAb)
timeFrame: approximately 24 months
measure: Expression level of CLDN18.2 in tumor tissues
timeFrame: approximately 24 months
measure: Overall survival (OS)
timeFrame: approximately 36 months
measure: Incidence and severity of AE
timeFrame: approximately 36 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: