An Open-Label, Multicenter, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Preliminary Antitumor Activity of HH160 Alone or in Combination With Other Antitumor Agents in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 299
- 试验地点
- 3
- 主要终点
- Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This study is evaluating the safety, side effects, how the body processes HH160, and its early anticancer activity when given alone or with other cancer treatments in participants with advanced solid tumors. The study will also identify the recommended dose for future studies. The trial includes two phases and is expected to last about 4 years, with treatment and follow-up lasting approximately 6-12 months each.
详细描述
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary antitumor activity of HH160 alone or in combination with antitumor agents in participants with advanced or solid tumors, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), gastroesophageal adenocarcinoma (GEA), head and neck squamous cell carcinoma, renal cell carcinoma (RCC), endometrial carcinoma, cervical cancer, ovarian cancer, small cell lung cancer, triple-negative breast cancer, urothelial carcinoma, and additional tumor types based on emerging clinical data.
The study will also identify the recommended phase 1 dose (RP2D) of HH160 monotherapy and/or in combination with other chemotherapy regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 to 75 years with signed informed consent.
- •Histologically or cytologically confirmed advanced solid tumors meeting phase-specific disease requirements.
- •At least 1 measurable lesion per RECIST v1.
- •Eastern Cooperative Oncology Group Performance Status (ECOG) Performance Status of 0 or 1 with life expectancy ≥ 12 weeks.
- •Adequate organ function based on protocol-specified laboratory criteria.
排除标准
- •Active leptomeningeal disease or uncontrolled/untreated brain metastases.
- •History of severe hypersensitivity reactions to monoclonal antibodies, bispecific antibodies, trispecific antibodies, or study drug components.
- •Other malignancy within 3 years prior to first dose, except specified curatively treated cancers.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
- •Significant bleeding risk, severe coagulopathy, gastrointestinal hemorrhage, or recent pulmonary hemorrhage/hemoptysis.
- •NOTE: Other eligibility criteria may apply.
研究组 & 干预措施
Phase 1b: Dose Expansion
Additional participants with selected advanced or metastatic solid tumors will receive HH160 alone or in combination with chemotherapy at selected expansion dose levels and schedules identified during phase 1a.
干预措施: HH160 (Drug)
Phase 1a Part 1 : Dose Escalation
Participants with advanced solid tumors will receive escalating doses of HH160
干预措施: HH160 (Drug)
Phase 1a Part 2: Safety Expansion
Participants with selected advanced or metastatic solid tumors will receive HH160 at dose levels determined to be tolerable during dose escalation to further evaluate safety and tolerability.
干预措施: HH160 (Drug)
结局指标
主要结局
Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From first dose of study drug to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 12 months
Assessed by treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of HH160
时间窗: From first dose through the end of Cycle 1 (approximately 1 month)
The MTD or MAD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 28%, or the highest dose administered, respectively.
Phase 1b: Recommended Phase 2 Dose (RP2D) of HH160
时间窗: From first dose through completion of Phase 1b dose optimization (up to 2 years)
RP2D is defined as the dose level selected based on the overall assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy
Phase 1b: Overall Response Rate (ORR)
时间窗: Up to 2 years
Defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) assessed by the investigator.
次要结局
- Phase 1a: Objective Response Rate (ORR)(Up to 2 years)
- Phase 1a: Time to Response (TTR)(Up to 2 years)
- Phase 1b: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of study drug to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 2 years)