A Phase Ib Clinical Study on the Efficacy, Safety, Tolerability, and Pharmacokinetics of HS-20093 in Patients With Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
研究概览
简要总结
HS-20093 is a humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells.
This is a phase 1b, open-label, multi-center study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of HS-20093 in patients with advanced gastric and gastroesophageal junction adenocarcinoma.
详细描述
The first approximately 20 eligible participants who meet the inclusion criteria and do not meet the exclusion criteria will receive intravenous infusion of 8.0 mg/kg HS-20093 once every three weeks (Q3W). Treatment will continue until objective disease progression or other treatment discontinuation criteria are met.
Based on preliminary safety, efficacy, and pharmacokinetic data, the sponsor may decide whether subsequent participants will continue the current dosing regimen (8.0 mg/kg, Q3W), switch to a lower dose (e.g., 6.0 mg/kg, Q3W), a higher dose (e.g., 10.0 mg/kg, Q3W), or transition to a dosing frequency of once every two weeks (with a single dose not exceeding 6.0 mg/kg).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least age of 18 years at screening, with no restrictions on gender.
- •Signed and dated Informed Consent Form.
- •Participants with pathologically or cytologically confirmed locally advanced unresectable or metastatic GC/GEJC, who have failed, or intolerant to standard therapies.
- •At least one extra measurable lesion according to RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~
- •Estimated life expectancy >12 weeks.
- •Agree to provide fresh or archival tumor tissue.
- •Good organ function.
- •Female subjects must not be pregnant at screening or have evidence of non-childbearing potential.
- •Men or women should be using adequate contraceptive measures throughout the study.
排除标准
- •Treatment with any of the following:
- •Previous or current treatment with B7-H3 targeted therapy.
- •Previous or current treatment with topoisomerase I inhibitors.
- •Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 14 days prior to the first scheduled dose of HS-20093
- •Prior treatment with a monoclonal antibody within 28 days prior to the first scheduled dose of HS-20093
- •Local radiotherapy for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first scheduled dose of HS-20093
- •Treatment with drugs that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug; or requiring treatment with these drugs during the study.
- •Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study.
- •Histology shows squamous cell carcinoma, undifferentiated carcinoma, or mixed tumors , such as adenosquamous carcinoma or other mixed tumors.
- •Any unresolved toxicities from prior therapy greater than Grade 1 according to CTCAE 5.0 or baseline status.
- •Presence of pleural effusion/ascites requiring clinical intervention.
- •Newly diagnosed brain metastases without treatment, or brain metastases that have not achieved stability despite treatment; presence of leptomeningeal metastasis or brainstem metastasis; presence of spinal cord compression.
- •History of other primary malignancies
- •Evidence of cardiovascular risk.
- •Severe, uncontrolled or active cardiovascular diseases.
- •Severe or poorly controlled hypertension.
- •Severe or poorly controlled diabetes.
- •Poorly controlled cancer-related pain.
- •The presence of active infectious diseases has been known: hepatitis B, hepatitis C and HIV.
- •Major surgery within 4 weeks prior to the first scheduled dose of HS-
- •Active infection requiring therapeutic intravenous antibiotics within 2 weeks prior to the first dose.
- •Clinically significant bleeding symptoms or marked hemorrhagic tendency within 1 month prior to the first dose of HS-
- •Serious arterial or venous thromboembolic events occurring within 3 months prior to the first dose of HS-
- •Active tuberculosis.
- •History of known interstitial pneumonia or immune-mediated pneumonitis.
- •History of active or prior autoimmune disease requiring systemic treatment.
- •Severe malnutrition.
- •Current hepatic encephalopathy, hepatorenal syndrome, or cirrhosis ≥ Child-Pugh class B.
- •Requires long-term glucocorticoid therapy.
- •Having undergone any major surgery within 4 weeks prior to the first dose.
- •Vaccination within 4 weeks prior to the first dose of HS-
- •History of severe allergy.
- •Previous history of serious neurological or mental disorders. Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator.
- •Currently enrolled in or participating in any other clinical study involving investigational interventions or other types of interventional medical research.
研究组 & 干预措施
HS-20093
Participants will receive HS-20093
干预措施: HS-20093 for injection (Drug)
结局指标
主要结局
Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
时间窗: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigators based on RECIST version 1.1\[Confirmed CR/PR assessment require at least one repeat (≥4 weeks)\]
次要结局
- PFS assessed by RECIST 1.1 criteria(From the first dose up to PD or death，whichever came first, assessed up to 24 months.)
- Unconfirmed ORR (uORR)(From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.)
- Duration of response (DoR)(From the first dose up to PD or death, whichever came first, assessed up to 24 months.)
- Incidence and severity of adverse events (AEs)(From the first dose until 90 days after the last dose)
- Cmax of HS-20093(At the end of Cycle 1 (each cycle is 21 days)")
- Tmax of HS-20093(At the end of Cycle 1 (each cycle is 21 days)")
- AUC0-t of HS-20093(At the end of Cycle 1 (each cycle is 21 days)")
- Incidence of anti-hs-20093 antibodies (ADAs)(From the first dose until 90 days after the last dose)