A Phase II Study of Toripalimab Combined With Sacituzumab Tirumotecan as Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
This is a prospective, multicenter, single-arm Phase II investigator-initiated trial evaluating neoadjuvant toripalimab plus sacituzumab tirumotecan (SKB264) in treatment-naive adults with resectable or potentially resectable, driver-negative non-small cell lung cancer (NSCLC). Eligible participants have stage II-IIIA or selected IIIB disease (T3N2 or T4N2) and will receive sacituzumab tirumotecan 5 mg/kg plus toripalimab 3 mg/kg intravenously on Day 1 every 2 weeks for up to 6 cycles. Participants deemed operable after multidisciplinary assessment will undergo definitive surgery. The primary endpoint is pathologic complete response. A Simon two-stage minimax design plans to enroll 30 participants.
详细描述
This prospective, multicenter, single-arm Phase II investigator-initiated trial evaluates neoadjuvant sacituzumab tirumotecan (SKB264), a TROP2-directed antibody-drug conjugate, plus the PD-1 antibody toripalimab in treatment-naive adults with resectable or potentially resectable, driver-negative NSCLC. Participants have stage II-IIIA or selected IIIB disease (T3N2 or T4N2). Sacituzumab tirumotecan 5 mg/kg and toripalimab 3 mg/kg are administered intravenously on Day 1 every 2 weeks for up to 6 cycles. Surgery is planned 4-6 weeks after the final neoadjuvant dose when the participant remains operable following multidisciplinary assessment. Tumor response is assessed using RECIST 1.1. Safety is assessed using NCI CTCAE version 5.0, including adverse events, serious adverse events, perioperative complications, and surgery delays or cancellations. The primary endpoint is pathologic complete response, defined as no residual viable tumor cells in the resected primary tumor and all resected lymph nodes. Major pathologic response is defined as residual viable tumor of 10% or less.
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
- •Signed informed consent obtained before any study procedure.
- •Age 18 to 75 years, male or female.
- •Histologically/cytologically confirmed, treatment-naive, resectable or potentially resectable NSCLC: stage II-IIIA and selected IIIB (T3N2, T4N2) per IASLC/UICC TNM 9th edition.
- •Disease staged as cTNM by PET-CT or by neck/chest/abdominal/pelvic CT plus whole-body bone scan and brain MRI.
- •Multidisciplinary team including thoracic surgeon judges lesion resectable or potentially resectable.
- •At least one measurable target lesion per RECIST 1.
- •ECOG performance status 0-
- •Adequate organ function (baseline, no transfusion, rh-EPO, or G-CSF within 2 weeks before first dose): neutrophils ≥1.5 ×10^9/L; platelets ≥100 ×10^9/L; hemoglobin ≥9 g/dL.
- •AST, ALT, ALP ≤2.5 × ULN; TBil ≤1.5 × ULN.
- •For liver metastases: AST/ALT ≤5 × ULN; TBil ≤2 × ULN.
- •For liver or bone metastases: ALP ≤5 × ULN.
- •Creatinine clearance (Cockcroft-Gault) ≥60 mL/min.
- •INR, APTT, PT ≤1.5 × ULN.
- •TSH within normal range; if TSH abnormal but T3 and free T4 normal, eligible.
- •Women of childbearing potential must have a negative pregnancy test within 7 days before first dose and use effective contraception during treatment and until 12 months after last dose; men with partners of childbearing potential must use effective contraception during treatment and until 12 months after last dose.
排除标准
- •Neuroendocrine histology component in tumor pathology.
- •Known EGFR sensitizing mutation or ALK fusion (for non-squamous NSCLC, EGFR/ALK status must be determined).
- •Other malignancy within 5 years, except those with clinically negligible metastatic risk and curative treatment intent (e.g., adequately treated carcinoma in situ as per protocol examples).
- •Severe or uncontrolled comorbidities, including symptomatic cerebrovascular events or liver disease at Child-Pugh grade ≥A.
- •History of allogeneic stem cell transplantation or solid organ transplantation.
- •Severe dry eye syndrome, severe meibomian gland dysfunction, severe blepharitis, or corneal disorders that may delay corneal healing.
- •History of interstitial lung disease requiring steroids, or active ILD.
- •HIV positive or diagnosed AIDS.
- •Active tuberculosis.
- •Uncontrolled active HBV infection (HBsAg positive with HBV-DNA above local upper limit of normal). HBV-DNA must be <500 IU/mL within 28 days before randomization/inclusion.
- •Active HCV infection (HCV antibody positive and HCV RNA positive).
- •Known hypersensitivity to toripalimab or sacituzumab tirumotecan (or excipients).
- •Live vaccine within 30 days before first dose (except inactivated vaccines allowed where specified by protocol, including local policy).
- •Any systemic or local anticancer treatment before first study treatment.
- •Use of traditional Chinese medicines with anticancer indication within 7 days before first dose, or need to continue such drugs during study.
- •Other investigational drug not discontinued for at least 5 half-lives or 2 months (whichever is longer) before first dose.
- •Any known or suspected autoimmune disease or immunodeficiency, except primary hypothyroidism (stable, not requiring hormones, or stable on physiologic hormone replacement) and stable type 1 diabetes mellitus with controlled blood glucose.
- •Medical or psychiatric conditions likely to cause premature discontinuation or compromise safety, sampling, or follow-up, including severe social or compliance risks.
- •Pregnancy or breastfeeding; unwillingness to use effective contraception as specified.
- •Any other condition considered unsuitable by investigator.
研究组 & 干预措施
Toripalimab plus sacituzumab tirumotecan
Participants will receive sacituzumab tirumotecan 5 mg/kg intravenously on Day 1 every 2 weeks combined with toripalimab 3 mg/kg intravenously on Day 1 every 2 weeks for up to 6 cycles as neoadjuvant therapy. Surgery will be performed after multidisciplinary assessment when appropriate. Postoperative or adjuvant treatment will be determined according to guidelines and investigator assessment.
干预措施: Sacituzumab Tirumotecan (SKB264) (Drug)
Toripalimab plus sacituzumab tirumotecan
Participants will receive sacituzumab tirumotecan 5 mg/kg intravenously on Day 1 every 2 weeks combined with toripalimab 3 mg/kg intravenously on Day 1 every 2 weeks for up to 6 cycles as neoadjuvant therapy. Surgery will be performed after multidisciplinary assessment when appropriate. Postoperative or adjuvant treatment will be determined according to guidelines and investigator assessment.
干预措施: Toripalimab (Drug)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: At definitive surgery, up to 18 weeks after first study treatment
Proportion of participants with no residual viable tumor cells in the resected primary tumor and all resected lymph nodes. Participants without surgery or evaluable surgical pathology will be counted as non-pCR.
次要结局
- Objective Response Rate (ORR)(Up to 18 weeks after first study treatment)
- Major Pathological Response (MPR) Rate(At definitive surgery, up to 18 weeks after first study treatment)
- R0 Resection Rate(At definitive surgery, up to 18 weeks after first study treatment)
- Pathological Downstaging Rate(At definitive surgery, up to 18 weeks after first study treatment)
- Event-Free Survival (EFS)(Up to 60 months from enrollment)
- Overall Survival (OS)(Up to 60 months from enrollment)
- Incidence of Adverse Events(From first study treatment through 90 days after the last study treatment or surgery, whichever occurs later)
研究者
Shaodong Hong
Principle Inverstigator
Sun Yat-sen University