Efficacy and Safety of Becotatug Vedotin (MRG003) Combined With Anti-PD1 as Maintenance Therapy for Recurrent and Metastatic Nasopharyngeal Carcinoma: A Randomized, Controlled, Multicenter Phase III Clinical Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
This multicenter randomized controlled Phase III trial assesses the efficacy and safety of becotatug vedotin plus anti-PD-1 antibody as maintenance therapy for recurrent/metastatic nasopharyngeal carcinoma. Eligible patients aged 18-75 must have stable disease or positive plasma EBV DNA after 4-6 cycles of first-line chemoimmunotherapy, with adequate organ function and good physical status. A total of 86 subjects will be randomly split 1:1: the control group receives single anti-PD-1 maintenance, while the experimental group gets anti-PD-1 combined with becotatug vedotin in 21-day cycles for up to 2 years. Regular blood tests and tumor scans will be performed to monitor efficacy and adverse events graded by CTCAE v5.0; biological samples will be collected for biomarker research with consent. The primary endpoint is IRC-reviewed progression-free survival, with secondary endpoints covering overall survival, tumor response rates and safety. Overseen by an independent ethics committee, the trial ensures full data confidentiality. Participants sign informed consent and can withdraw anytime without interference to their routine cancer care, exploring a superior maintenance regimen for this high-risk NPC group.
详细描述
The therapeutic outcomes of patients with recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) remain unsatisfactory for high-risk subgroups after standard first-line chemoimmunotherapy. Numerous previous studies have shown that anti-PD-1 immune checkpoint inhibitors (ICIs) deliver prominent anti-tumor activity in frontline treatment for R/M NPC. Large-scale Phase III trials including CAPTAIN-1st, JUPITER-02 and RATIONALE-309 confirmed that chemotherapy combined with PD-1 monoclonal antibodies greatly prolonged patients' progression-free survival (PFS) and became the standard first-line regimen. However, a large proportion of patients only reach stable disease (SD) or retain positive plasma EBV DNA after 4-6 cycles of chemoimmunotherapy, and single PD-1 maintenance barely offers durable tumor control for this population, with median PFS shorter than 5 months.
In addition, antibody-drug conjugates (ADCs) represented by becotatug vedotin have demonstrated robust anti-tumor activity in R/M NPC. Phase II clinical data showed that single-agent becotatug vedotin achieved an objective response rate (ORR) close to 47%, and its combination with PD-1 inhibitors yielded an ORR as high as 66.7% in heavily pretreated NPC patients with manageable adverse reactions. Based on this preclinical and early clinical evidence, investigators hypothesize that adding becotatug vedotin to PD-1 maintenance therapy can bring extra survival benefits to high-risk NPC patients with residual tumor burden after frontline chemoimmunotherapy.
Investigators previously analyzed real-world and clinical trial data of patients receiving PD-1 monotherapy maintenance and verified the limited efficacy of single-agent immunotherapy in subjects with SD or persistent positive EBV DNA after first-line treatment. This study aims to design a prospective, multicenter, randomized controlled Phase III clinical trial to evaluate the efficacy and safety of maintenance therapy with becotatug vedotin combined with anti-PD-1 antibody versus single-agent anti-PD-1 antibody for recurrent and metastatic nasopharyngeal carcinoma patients who achieved stable disease or positive plasma EBV DNA following first-line chemotherapy plus anti-PD-1 treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Aged between 18 and 75 years at diagnosis, regardless of gender;
- •Histologically confirmed nasopharyngeal carcinoma;
- •Patients with advanced nasopharyngeal carcinoma with confirmed distant metastasis (Stage IVb per AJCC 8th edition; Stage IV per AJCC 9th edition), or recurrent nasopharyngeal carcinoma unsuitable for locoregional or curative therapy;
- •Achieved stable disease (SD) assessed per RECIST v1.1 or maintained positive plasma EBV DNA after 4 to 6 cycles of first-line chemotherapy combined with immunotherapy;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- •Expected survival of at least 12 weeks;
- •No prior systemic chemotherapy administered within 6 months before diagnosis (excluding patients with disease progression more than 6 months after neoadjuvant chemotherapy, adjuvant chemotherapy, or definitive concurrent chemoradiotherapy);
- •At least one measurable lesion as defined by RECIST v1.1;
- •Adequate organ and bone marrow function as defined below:
- •HGB ≥90 g/L, WBC ≥4×10⁹/L, PLT ≥100×10⁹/L.
- •Liver function: TBIL <1.5 × ULN; ALT and/or AST <2.5 × ULN. For patients with liver metastases, ALT or AST <5 × ULN. For patients with liver or bone metastases, ALP <5 × ULN.
- •Renal function: creatinine <1.5 × ULN.
- •Coagulation: INR of PT / PTT <1.5 × ULN;
- •Able to provide written informed consent and comply with all protocol-specified procedures including laboratory tests and follow-up visits;
- •Female subjects of childbearing potential and male subjects with childbearing potential partners must agree to use effective contraception from screening through 6 months after the last dose of study treatment (e.g., condoms, regular oral contraceptives as prescribed).
排除标准
- •Peripheral neuropathy ≥ Grade 2 (per NCI-CTCAE v5.0);
- •History of hypersensitivity to any study drug;
- •Expected survival less than 3 months;
- •Active hepatitis B (positive HBsAg or HBcAb with HBV DNA ≥ 2000 IU/mL) or active hepatitis C (positive HCV antibody with HCV RNA above the lower limit of quantification at the study site). For patients with normal liver function receiving antiviral therapy, eligibility shall be determined by the investigator;
- •Patients with positive HIV antibody;
- •Active bacterial, fungal, viral infection requiring systemic treatment, or interstitial pneumonia within 1 week prior to the first administration of study drugs;
- •Received anti-tumor therapies including chemotherapy, small-molecule inhibitors, immunotherapy (e.g., interleukins, interferons, thymosins) within 4 weeks or 5 half-lives (whichever is shorter, with a minimum interval of 2 weeks) before the first dose of study drugs;
- •Received anti-tumor therapies including chemotherapy, small-molecule inhibitors, immunotherapy (e.g., interleukins, interferons, thymosins) within 4 weeks or 5 half-lives (whichever is shorter, with a minimum interval of 2 weeks) before the first dose of study drugs;
- •Underwent major surgery within 3 months prior to the first dose, or planned to receive major surgery during the study period;
- •Severe thromboembolic events within 6 months before screening, such as cerebrovascular accidents (including transient ischemic attack) and pulmonary embolism;
- •Active malignant tumors within 2 years prior to the first administration of study drugs, excluding nasopharyngeal carcinoma under investigation and any locally curable tumors that have received radical treatment (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ);
- •Severe cardiovascular diseases within 6 months before enrollment, including but not limited to:
- •Acute myocardial infarction, unstable angina, coronary angioplasty or stenting, deep vein thrombosis, stroke;
- •New York Heart Association (NYHA) Class III or IV congestive heart failure, or left ventricular ejection fraction (LVEF) < 50%;
- •Electrocardiogram (ECG) abnormalities of significant clinical relevance at screening as assessed by the investigator;
- •Pregnant or breastfeeding women;
- •Presence of any severe and/or uncontrolled diseases that, in the investigator's judgment, may interfere with the patient's participation in the study (including but not limited to uncontrolled diabetes, dialysis-dependent renal disease, severe liver disease, life-threatening autoimmune and hemorrhagic diseases, substance abuse, neurological disorders);
- •Any other conditions deemed inappropriate for participation by the investigator.
结局指标
主要结局
Progression free survival
时间窗: From randomization to 10 months
Progression free survival is defined as the time interval between randomization and the first recording of tumor progression (evaluated according to RECIST 1.1 criteria, regardless of continued treatment) or death from any cause
次要结局
- overall survival(From randomization to 3 years)
- Second-line progression-free survival(From enrollment to 20 months)
- Duration of response(From enrollment to the end of treatment at 3 weeks)
- Objective response rate(From enrollment to the end of treatment at 3 weeks)
- Disease control rate(From enrollment to the end of treatment at 3 weeks)
- Incidence of Treatment-Emergent Adverse Events(From enrollment to the end of treatment at 3 weeks)
研究者
XIANG YANQUN
Clinical Professor
Sun Yat-sen University