A Phase Ib/II Clinical Study Evaluating the Safety, Efficacy, Tolerability, and Pharmacokinetics of HS-10516 Combination Therapy in Patients With Advanced Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Phase Ib: MTD or RP2D
研究概览
简要总结
This is a multicenter, open-label, Phase Ib/II clinical study evaluating the safety, efficacy, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profiles of HS-10516 in combination with lenvatinib in patients with advanced clear cell renal cell carcinoma (ccRCC) who have progressed after receiving at least one prior line of systemic therapy. The study comprises two distinct phases: a dose exploration phase and a proof-of-concept phase.
详细描述
The study will commence with a dose exploration phase employing a safety lead-in approach. Treatment cycles are set at 28 days, with investigational product administration continuing until disease progression or meeting other treatment discontinuation criteria. Each dose level will enroll 3-6 participants for dose-limiting toxicity (DLT) assessment to evaluate the tolerability, safety, and PK/PD profiles of HS-10516 combined with lenvatinib. The Safety Review Committee (SRC) will determine subsequent dose levels for exploration through joint deliberation. If all predefined dose levels prove intolerable, the SRC may authorize exploration of lower dose levels. Additionally, PK expansion cohorts (up to 12 participants per cohort) may be implemented in suitable dose levels.
Following identification of safe dose levels in the exploration phase, 1-2 dose cohorts will advance to the proof-of-concept phase, with each cohort enrolling up to 40 participants to further assess therapeutic efficacy and safety.
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
- •Men or women aged more than or equal to (≥) 18 years.
- •Histologically confirmed unresectable, locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) with disease progression during or after receiving ≥1 prior line of systemic therapy in the advanced setting.
- •Patients have at least one target lesion according to RECEST 1.
- •The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required). Patients with only brain and/or bone lesions as target lesions will not be included.
- •ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
- •Estimated life expectancy greater than (>) 12 weeks.
- •Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 12 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
- •Females must have the evidence of non-childbearing potential
- •Sign informed consent form.
排除标准
- •Prior or Current Treatments:
- •Previous or current use of hypoxia-inducible factor inhibitors.
- •Previous or current use of lenvatinib.
- •Use of Chinese herbal medicine with antitumor indications within 2 weeks prior to the first dose or requirement for such treatment during the study.
- •Administration of cytotoxic chemotherapy or other systemic antitumor therapies (e.g., endocrine therapy, molecular targeted therapy) within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose, or requirement for such treatments during the study.
- •Use of large-molecule antitumor drugs within 4 weeks prior to the first dose or requirement for such treatment during the study.
- •Use of CYP2C19 strong inhibitors/inducers or narrow therapeutic index sensitive substrates within 7 days prior to the first dose, or requirement for continued use during the study.
- •Local radiotherapy (except brain radiotherapy; see Criterion 6) within 2 weeks prior to the first dose, or >30% bone marrow irradiation/large-field radiotherapy within 4 weeks prior to the first dose.
- •Major surgery (e.g., craniotomy, thoracotomy, laparotomy; Grade 3/4 per Chinese Medical Technical Clinical Application Regulations) within 4 weeks prior to the first dose.
- •Participation in other interventional clinical trials within 4 weeks prior to the first dose or within 5 half-lives of investigational drugs (whichever is longer).
- •Resting pulse oximetry <92% at screening.
- •Severe pulmonary dysfunction requiring intermittent/long-term oxygen therapy.
- •Unresolved Grade >1 toxicities from prior anti-tumor therapy (per CTCAE v5.0).
- •History of second primary malignancy.
- •Known or suspected active CNS metastases/leptomeningeal disease.
- •Inadequate bone marrow reserve or serious organ dysfunction.
- •Severe, uncontrolled, or active cardiovascular disease.
- •Severe or poorly controlled diabetes.
- •Severe or poorly controlled hypertension.
研究组 & 干预措施
Phase Ib (Dose exploration phase) Phase II (Proof-of-concept phase)
Treatment cycles are set at 28 days, with investigational product administration continuing until disease progression or meeting other treatment discontinuation criteria.
干预措施: HS-10516 + Lenvatinib (Drug)
结局指标
主要结局
Phase Ib: MTD or RP2D
时间窗: Up to 3 months
MTD or RP2D was determined by number of participants with DLT in dose levels. A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).
Phase II: Objective Response Rate (ORR)
时间窗: Up to 12 months.
The percentage of patients who have achieved complete response and partial response, according to response evaluation criteria in solid tumors (RECIST) 1.1 by investigator's assessment.
次要结局
- Incidence and severity of treatment-emergent adverse events(Up to 36 months.)
- Duration of response (DoR)(Up to 24 months.)
- AUC0-t(Up to 24 months.)
- Disease control rate (DCR)(Up to 24 months.)
- Progression-free survival (PFS)(Up to 24 months.)
- Overall survival (OS)(Up to 3 years.)
- Maximum plasma concentration (Cmax)(Up to 24 months.)
- Time of maximum concentration (Tmax)(Up to 24 months.)