A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SKB315 for Injection in Patients With Advanced Solid Tumors Expressing Claudin18.2
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 246
- 试验地点
- 2
- 主要终点
- Phase 1b: Objective Response Rate (ORR)
研究概览
简要总结
This is a multicenter, open-label, multiple-dose dose finding and expansion study to evaluate the safety, tolerability, pharmacokinetic(PK) profile, and anti-tumor efficacy of SKB315 for injection in patients with advanced solid tumors.
详细描述
This is a multicenter, open-label, multiple-dose dose finding and expansion study to evaluate the safety, tolerability, PK profile, and anti-tumor efficacy of SKB315 for injection in patients with advanced solid tumors.The study is divided into Phase 1a and Phase 1b: Phase 1a is a dose escalation study to determine the maximum tolerated dose(MTD); Phase 1b （monotherapy）is a dose expansion study to conduct preliminary evaluation of anti-tumor efficacy and further evaluation of safety, tolerability, PK, and immunogenicity of SKB315.Phase 1b（combination with Tagitanlimab and Capecitabine） is designed to evaluate the efficacy and safety of SKB315 combination with Tagitanlimab and Capecitabine in CLDN18.2-positive of patients with locally advanced, recurrent, or metastatic gastric and esophagogastric junction adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ia&Ib(monotherapy):1) Male or female patients aged 18 to 80 years (inclusive) at the time of signing the informed consent form (ICF); 2) Patients with histologically and/or cytologically confirmed advanced solid tumors who have failed standard of care, or who have no available standard of care regimen, or who are unqualified for standard of care; 3) Consent to provide archival or fresh tumor tissue slides for immunohistochemistry (IHC) assessment, and advanced solid tumors with Claudin 18.2 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) Have recovered to ≤ Grade 1 (according to national cancer institute (NCI) common terminology criteria adverse events (CTCAE) V5.0) from previously treated toxicity prior to the first dose of study treatment; 9) Patients of childbearing potential (male or female) must use effective medical contraception during the study and for 6 months after the end of dosing; 10) Patients voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol-specified visits and relevant procedures.
- •Phase Ib (combination) Inclusion criteria
- •Age 18 to 80 years old (including boundary values);
- •Histopathologically confirmed unresectable locally advanced, recurrent, or metastatic adenocarcinoma of the gastric and gastroesophageal junction 3 positive CLDN18.2 expression in tumor tissue;
- •4. ECOG score 0-1;
- •Expected survival ≥3 months;
- •There is at least one measurable lesion that meets the RECIST 1.1 criteria;
- •Adequate bone marrow and organ function
排除标准
- •Ia&Ib(monotherapy)1) Received other drugs in clinical study, major surgeries, or any other anti-tumor therapies within 4 weeks prior to the first dose of study treatment; 2) Received any previous therapy targeting Claudin18.2; 3) Plan to receive any other anti-tumor therapy during the study; 4) Received strong cytochrome P450 3A4(CYP3A4) inhibitors or inducers within 2 weeks prior to the first dose of study treatment or within 5 half-lives of drug elimination, whichever is longer; 5) Have other malignancies within 5 years prior to signing of ICF; 6) Pregnant or lactating women; 7) Known history of allergy to any component of SKB315 or other monoclonal antibodies (mAbs); 8) Known history of alcohol abuse (consumption of more than 14 units of alcohol per week or drug abuse); 9) Patients with active hepatitis B or hepatitis C; 10) Human immunodeficiency virus (HIV) positive; 11) Active severe digestive disease; 12) History of major cardiovascular diseases 13) Confirmed serious lung disease or lung disease that may impair the respiratory reserve function of the patient as judged by the investigator; 14) History of serious dementia, altered mental status, or any psychiatric disorder; 15) Concomitant or known metastases to brain or central nervous system; 16) Have clinically significant systemic diseases that may adversely affect the safety of the study; 17) Subjects who may have poor compliance with the clinical study or have other factors based on which the investigator considers that the subjects are not appropriate to participate in the study.
- •Ib(combination)
- •HER2 expression in tumor tissue is positive.
- •Has a history of brain metastases.
- •Additional malignancy within the five years prior to the first administration.
- •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.
- •A history of immunodeficiency, including a positive HIV test; Presence of active hepatitis B or hepatitis C.
- •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.
研究组 & 干预措施
Phase 1a：Dose escalation
Eleven dose levels are tentatively planned for Phase 1a
干预措施: SKB315 for injection (Drug)
Phase 1b: Dose expansion
The dose of SKB315 for injection in Phase 1b is selected based on the Phase 1a monotherapy dose escalation study.
干预措施: SKB315 for injection (Drug)
Phase 1b combination
The dose of SKB315 for injection in Phase 1b is selected based on the Phase 1a monotherapy dose escalation study.
干预措施: SKB315 for injection (Drug)
结局指标
主要结局
Phase 1b: Objective Response Rate (ORR)
时间窗: 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.
Phase 1a: Dose Limiting Toxicities (DLT)
时间窗: From data of initial dose until up to 21/28 days for treatment
Incidence of Dose Limiting Toxicities
次要结局
- Overall Survival (OS)(Up to 2 years)
- Duration of Response (DOR)(Up to 2 years)
- Progression Free Survival (PFS)(Up to 2 years)