A Multicenter, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of Tislelizumab in Combination With Lenvatinib in Patients With Selected Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 58
- 试验地点
- 13
- 主要终点
- Safety Run-in: Number of Participants With Adverse Events (AEs)
研究概览
简要总结
This clinical trial evaluated the safety and potential benefits of combining two cancer treatments, tislelizumab and lenvatinib, in Chinese participants with advanced or metastatic cancers, including lung, head and neck, bladder, kidney, and stomach cancer. The study included two parts: the first part assessed how safe the drug combination was, and the second part examined how well it worked.
A small group of participants initially received the drugs to determine the appropriate dose, and if the treatment was well tolerated, additional participants were treated at that dose. Participants remained on the treatment unless their cancer progressed, they experienced serious side effects, or they chose to stop.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants had signed an informed consent form and were able to comply with all study requirements.
- •Participants had a histologically and/or cytologically confirmed diagnosis of advanced solid tumors, which included one of the following types:
- •Non-Small Cell Lung Cancer (NSCLC)
- •Squamous Cell Carcinoma of the Head and Neck (SCCHN)
- •Gastric Cancer (GC)
- •Urothelial Carcinoma (UC)
- •Renal Cell Carcinoma (RCC)
- •Participants had at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.
- •Tumor tissue samples (approximately 10 unstained slides) were provided for central laboratory assessment of programmed death-ligand 1 (PD-L1) expression in the NSCLC cohort during the screening period. These samples were also used for retrospective exploratory biomarker analyses related to treatment response and resistance across the NSCLC, SCCHN, UC, or Gastric Cancer (GC) cohorts, in a central or designated test laboratory approved by BeiGene.
- •Participants had an Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
排除标准
- •For participants in the NSCLC cohort, those with active leptomeningeal disease or uncontrolled, untreated brain metastases were excluded. In cohorts other than NSCLC, any participant with known leptomeningeal disease or brain metastases was excluded.
- •Participants who had received prior therapy with lenvatinib, or with antibodies targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), or any other agents specifically targeting T-cell costimulatory or immune checkpoint pathways, were excluded.
- •Participants with a history of interstitial lung disease, non-infectious pneumonitis, or any uncontrolled pulmonary conditions (including but not limited to pulmonary fibrosis or acute lung diseases) were excluded.
- •Participants who were unable to swallow capsules, or who had diseases or previous procedures that significantly affected gastrointestinal function such as malabsorption syndrome, surgical resection of the stomach or small bowel, bariatric surgery, symptomatic inflammatory bowel disease, or partial/complete bowel obstruction were excluded.
- •Participants who had experienced clinically significant bleeding (classified as Grade 2 or higher according to the Common Terminology Criteria for Adverse Events [CTCAE]) within 21 days prior to the first dose were excluded.
- •Note: Additional protocol-defined inclusion and exclusion criteria may have applied.
研究组 & 干预措施
Safety Run In
Participants with advanced or metastatic unresectable solid tumors were enrolled to receive 400 mg of tislelizumab administered on Day 1 of each 6-week cycle, along with 20 mg of lenvatinib self-administered orally once daily, to determine the recommended Part 2 dose (RP2D).
干预措施: lenvatinib (Drug)
Safety Run In
Participants with advanced or metastatic unresectable solid tumors were enrolled to receive 400 mg of tislelizumab administered on Day 1 of each 6-week cycle, along with 20 mg of lenvatinib self-administered orally once daily, to determine the recommended Part 2 dose (RP2D).
干预措施: Tislelizumab (Drug)
Part 2: Squamous Cell Carcinoma of the Head and Neck (SCCHN) Cohort
Participants with previously untreated, advanced or metastatic SCCHN received tislelizumab (400 mg administered intravenously [IV] every 6 weeks [Q6W]) in combination with lenvatinib (20 mg taken orally once daily [QD]) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination.
干预措施: lenvatinib (Drug)
Part 2: Squamous Cell Carcinoma of the Head and Neck (SCCHN) Cohort
Participants with previously untreated, advanced or metastatic SCCHN received tislelizumab (400 mg administered intravenously [IV] every 6 weeks [Q6W]) in combination with lenvatinib (20 mg taken orally once daily [QD]) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination.
干预措施: Tislelizumab (Drug)
Part 2: Renal Cell Carcinoma (RCC) Cohort
Systemic therapy naive participants with advanced or metastatic RCC received tislelizumab (400 mg IV Q6W) plus lenvatinib (20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination.
干预措施: lenvatinib (Drug)
Part 2: Renal Cell Carcinoma (RCC) Cohort
Systemic therapy naive participants with advanced or metastatic RCC received tislelizumab (400 mg IV Q6W) plus lenvatinib (20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination.
干预措施: Tislelizumab (Drug)
Part 2: Non-Small Cell Lung Cancer (NSCLC) Cohort
Participants with NSCLC expressing programmed cell death-ligand 1 (PD-L1) in ≥1% of tumor cells (TC ≥1%) and who had not received prior systemic therapy received tislelizumab (400 mg IV Q6W) and lenvatinib (20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination; this cohort was closed early based on emerging external data.
干预措施: lenvatinib (Drug)
Part 2: Non-Small Cell Lung Cancer (NSCLC) Cohort
Participants with NSCLC expressing programmed cell death-ligand 1 (PD-L1) in ≥1% of tumor cells (TC ≥1%) and who had not received prior systemic therapy received tislelizumab (400 mg IV Q6W) and lenvatinib (20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination; this cohort was closed early based on emerging external data.
干预措施: Tislelizumab (Drug)
Part 2: Gastric Cancer (GC) Cohort
Participants with advanced GC who had received one prior line of systemic therapy were enrolled to receive tislelizumab and lenvatinib at the RP2D (tislelizumab 400 mg IV Q6W; lenvatinib 20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination; this cohort was closed early due to changes in the first-line standard of care.
干预措施: lenvatinib (Drug)
Part 2: Gastric Cancer (GC) Cohort
Participants with advanced GC who had received one prior line of systemic therapy were enrolled to receive tislelizumab and lenvatinib at the RP2D (tislelizumab 400 mg IV Q6W; lenvatinib 20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination; this cohort was closed early due to changes in the first-line standard of care.
干预措施: Tislelizumab (Drug)
Part 2: Urothelial Cancer (UC) Cohort
Participants with cisplatin ineligible, systemic therapy naive advanced UC, were to be treated with tislelizumab (400 mg IV Q6W) and lenvatinib (20 mg orally QD). This cohort was closed prior to any participant enrollment based on emerging external data.
干预措施: lenvatinib (Drug)
Part 2: Urothelial Cancer (UC) Cohort
Participants with cisplatin ineligible, systemic therapy naive advanced UC, were to be treated with tislelizumab (400 mg IV Q6W) and lenvatinib (20 mg orally QD). This cohort was closed prior to any participant enrollment based on emerging external data.
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Safety Run-in: Number of Participants With Adverse Events (AEs)
时间窗: From first dose through the end of the safety run-in part, up to 124 days; The DLT observation period was 28 days after first dose.
An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it is related to the study drug. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: * Resulted in death * Was life-threatening * Required hospitalization or prolongation of existing hospitalization * Resulted in disability/incapacity * Was a congenital anomaly/birth defect * Was considered a significant medical AE by the investigator based on medical judgement. A dose-limiting toxicity (DLT) was defined as a Grade 3 or 4 hematologic or nonhematologic toxicity occurring during the DLT assessment window and deemed related to one or more study drugs by the investigator.
Overall Response Rate (ORR)
时间窗: From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months)
Overall response rate is defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments. CR is defined as the disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Progression Free Survival (PFS)(From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months))
- Duration of Response (DOR)(From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months))
- Disease Control Rate (DCR)(From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months))
- Number of Participants Experiencing Adverse Events (AEs)(From first dose of study drug to 30 days after last dose, up to the study completion date of 10 July 2024 (up to 32.5 months))
- Overall Survival (OS)(From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months))