SKB315 in Combination Therapy in Patients With Advanced or Metastatic GC/ GEJ Adenocarcinoma

This study is a multicenter,open-label,randomized, phase II clinical study conducted in China. The purpose of this study is to evaluate the efficacy of SKB315 plus PD-1 inhibitor ±capecitabine in patients with Unresectable Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

This study will also evaluate efficacy, physical function, safety, and tolerability of SKB315 combination, as well as Pharmacokinetics (PK) of SKB315 and the immunogenicity profile of SKB315 will be evaluated as well.

• Tislelizumab (Drug): Tislelizumab will be administered as the protocol described
• SKB315 for injection (Drug): Tislelizumab will be administered as the protocol described
• Capecitabine (Drug): Capecitabine will be taken orally as the protocol described

Primary outcomes

• Objective Response Rate (ORR) [up to 2 years]: The sum of the number of cases with Complete Response (CR) and Partial Response (PR) in all treated tumor patients (CR + PR) divided by the total number of cases.

Secondary outcomes

• Duration of Response (DOR) [up to 2 years]: Time from the start of the first assessment of CR or PR in tumor patients to PD or death due to any reason.
• Progression Free Survival (PFS) [up to 2 years]: Time from start of treatment to progression of disease (PD) or death, whichever occurs first, in patients with tumors.
• Overall Survival (OS) [up to 2 years]: Time from start of treatment to death due to any reason.
• Safety and tolerability assessed by adverse events (AEs) [Until 90 days after the end of treatment]: An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
• Time to Response (TTR) [up to 2 years]: Time from the start of treatment to the first assessment of CR or PR in tumor patients.
• Disease Control Rate (DCR) [up to 2 years]: Proportion of patients with best overall response of CR, PR, or SD and without PD or death due to any reason at the time of assessment in tumor patients.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Locally advanced unresectable or metastatic gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma and have histologically confirmed adenocarcinoma
2. No previous systemic therapy for locally advanced unresectable or metastatic gastric/GEJ cancer.
3. Consent to provide archival or fresh tumor tissue slides for immunohistochemistry (IHC) assessment, and advanced solid tumors with Claudin 18.2 and PD-L1 expression as determined by IHC;
4. Presence of at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;
5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1;
6. Estimated survival ≥ 3 months as judged by the investigator;
7. Adequate organ and bone marrow function (no blood components and cytokines are allowed within 2 weeks prior to the first dose) ;
8. Patients of childbearing potential (male or female) must use effective medical contraception during the study and for 6 months after the end of dosing;

Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled brain metastasis
2. Diagnosed with gastric or GEJ adenocarcinoma with positive HER2
3. Received other drugs in clinical study, major surgeries, or any other antitumor therapies within 4 weeks prior to the first dose of study treatment;
4. Patients with active hepatitis B or hepatitis C;
5. Patients have significant gastric bleeding
6. The presence of clinically uncontrollable third interspace fluid
7. Have clinically significant systemic diseases that may adversely affect the safety of the study;
8. Patients who may have poor compliance with the clinical study or have other factors based on which the investigator considers that the patients are not appropriate to patients in the study.

• Yi Ba, professor, Principal investigator, Peking Union Medical College