Sacituzumab Tirumotecan in Combination With Anlotinib in Previously Treated Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC): A Prospective, Single-Arm, Phase II Study (STAR-01)
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Sichuan University
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
概览
简要总结
This is an single-arm, multicenter phase II study to evaluate the safety and efficacy of Sacituzumab Tirumotecan (sac-TMT) plus anlotinib in previously treated extensive-stage small cell lung cancer (ES-SCLC). The study is expected to enroll up to 33 eligible patients.
详细描述
Extensive-stage small cell lung cancer (ES-SCLC) is among the most aggressive lung cancer subtypes, with rapid progression and poor prognosis. Despite first-line immunotherapy plus chemotherapy improving outcomes, most patients relapse within one year and face limited options. Topotecan, the standard second-line therapy, yields only 10-20% ORR and median PFS of ~3 months. Therefore, identifying novel therapeutic strategies with improved efficacy in ES-SCLC represent an urgent unmet medical need.
Sacituzumab tirumotecan, a structurally optimized Trop-2-directed ADC, and anlotinib, a multi-target TKI inhibiting VEGFR, FGFR, and MET, offer complementary mechanisms of action. We hypothesize that their combination may synergistically overcome acquired resistance to chemotherapy and immunotherapy, providing a novel therapeutic strategy for previously treated ES-SCLC.
Eligible participants will receive Sacituzumab Tirumotecan (4mg/Kg intravenously on Day 1, Q2W) plus Anlotinib (8 mg orally once daily on Days 1-14, Q3W). The primary objective is Objective Response Rate (ORR), and the secondary objectives including but not limited Progression-Free Survival (PFS), Overall Survival (OS) and Disease control response (DCR) .
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.Voluntary participation with written informed consent obtained prior to any study-specific procedures.
- •2.Age ≥ 18 years and ≤ 75 years, regardless of sex.
- •3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •4.Life expectancy of at least 3 months.
- •5.Histologically or cytologically confirmed small cell lung cancer (SCLC) based on pathology and immunohistochemistry/immunophenotyping results; disease staged as extensive-stage SCLC (ES-SCLC) according to the Veterans Administration Lung Study Group (VALG) staging system.
- •6.Disease progression (at the time of enrollment) after at least two cycles of platinum-based systemic therapy with or without PD-1/L1 inhibitors; no more than two prior lines of therapy.
- •Note: Adjuvant therapy is considered one prior line if disease progression occurs during treatment or within 6 months of the last adjuvant dose.
- •7.At least one measurable lesion as defined by RECIST version 1.
- •Lesions previously treated with local therapy may be considered target lesions only if progression has been clearly documented at that site post-treatment. Brain lesions as sole target lesions are not acceptable.
- •8.Adequate bone marrow function without transfusion or growth factor support within 14 days prior to screening: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L.
排除标准
- •1.History of other primary malignancies within 5 years prior to signing informed consent, except for: radically treated malignancies with no recurrence within 5 years; adequately treated non-melanoma skin cancer, cervical carcinoma in situ, thyroid cancer, or other malignancies considered cured.
- •2.Prior pathological diagnosis of combined small cell lung cancer (e.g., mixed SCLC and NSCLC), transformed NSCLC (SCLC transformed to NSCLC), or transformed SCLC (NSCLC transformed to SCLC).
- •3.Prior anti-tumor therapy within specified washout periods before first study dose: chemotherapy, radiotherapy, biologics, endocrine therapy, immunotherapy within 4 weeks; topical anti-tumor agents within 5 half-lives; nitrosoureas or mitomycin C within 6 weeks; oral fluoropyrimidines or small-molecule targeted agents within 5 half-lives; anti-tumor traditional Chinese medicine within 2 weeks.
- •4.Treatment with any other investigational drug or therapy within 4 weeks prior to first study dose.
- •5.Prior or current use of topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads (e.g., topotecan, irinotecan, trastuzumab deruxtecan, sacituzumab govitecan, datopotamab deruxtecan \[DS-1062\]).
- •6.Brain metastases unless asymptomatic (stable for ≥4 weeks, requiring ≤10 mg/day prednisone or equivalent for ≥14 days prior to first dose, and no significant peritumoral edema on imaging); leptomeningeal or brainstem metastases; spinal cord compression (radiographically confirmed, symptomatic or asymptomatic); bone marrow metastases.
- •7.Imaging evidence of tumor lesions located ≤5 mm from major blood vessels, invading major vessels, or assessed by the investigator as having high risk of major bleeding during the study.
- •8.History of deep vein or arterial thromboembolic events within 6 months (e.g., cerebrovascular accident including TIA, deep vein thrombosis, pulmonary embolism); DVT adequately treated or superficial vein thrombosis with low bleeding risk per investigator may be enrolled.
- •9.Prior treatment-related toxicities (CTCAE v5.0) ≥ Grade 2, except for alopecia, residual neurotoxicity, or stable hypothyroidism on hormone replacement.
- •10.Major surgery (excluding biopsy or vascular access) or significant trauma within 4 weeks prior to first study dose, or planned elective surgery during the study period.
研究组 & 干预措施
Experimental Arm
Participants will receive sacituzumab tirumotecan in combination with anlotinib. Sacituzumab tirumotecan will be administered intravenously, and anlotinib will be administered orally, according to the dosing schedule specified in the study protocol. The treatment will continue until disease progression, unacceptable toxic effects, withdrawal from the trial, or death or other protocol-defined discontinuation criteria are met, whichever occurred first.
干预措施: Sacituzumab Tirumotecan and Anlotinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 24 months
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response.
次要结局
- Progression Free Survival (PFS)(24 months)
- Overall Survival (OS)(24 months)
- Disease control response (DCR)(24 months)
- Duration of response (DoR)(24 months)
- Progression-free survival (PFS) rate of 6 months(6 months)
- Progression-free survival (PFS) rate of 1 year(1 year)
- Incidence of Adverse Events(From start of treatment through 60 days after last treatment, approximately 1 year)
研究者
You Lu
Chief of Thoracic Cancer Ward
Sichuan University