An International, Multicenter, Open-label, Randomized, Comparative Study of the Efficacy and Safety of RPH-002 and Erbitux® in Patients With Unresectable Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 161
- 试验地点
- 34
- 主要终点
- Objective response rate (%) (ORR)
研究概览
简要总结
The primary objective of the study is to evaluate the comparability of efficacy, safety, and immunogenicity of RPH-002 and Erbitux® when administered in combination with docetaxel and cisplatin as first-line therapy in patients with advanced head and neck squamous cell carcinoma
详细描述
This study is a international, multicenter, open-label, randomized, parallel-group Phase III study
The study will include the following periods:
- Screening Period 1
Includes Days -14 to -1 (prior to the first administration of the investigational product/comparator) 2. Main Period (Period 1)
The main study period includes Days 1-126
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
盲法说明
Open label
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
- •Main Period (Period 1)
- •A voluntarily signed and dated Informed Consent form (ICF) of the patient
- •Histologically confirmed squamous cell carcinoma of the head and neck
- •Documented unresectable locoregional recurrence or distant metastases, or progression after prior chemoradiotherapy or combination therapy completed >3 months before screening, not amenable to local treatment (except cases with high risk of tumor lysis or bleeding), or newly diagnosed metastatic disease not previously treated with systemic therapy. Study treatment is first-line therapy
- •At least one measurable lesion per RECIST 1.1
- •Karnofsky performance status ≥70%
- •Screening laboratory values within the following limits (per local lab normal ranges):
- •Hemoglobin ≥90 g/L
- •Leukocytes ≥3.0 × 10^9/L
- •Neutrophils ≥1.5 × 10^9/L
- •Platelets ≥100 × 10^9/L
- •Total bilirubin ≤2 × Upper Limit of Normal (ULN)
- •Aspartate aminotransferase (AST) ≤3 × ULN
- •Alanine aminotransferase (ALT) ≤3 × ULN
- •Estimated glomerular filtration rate (eGFR) ≥60 mL/min
- •Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt
- •Ability and willingness to comply with study protocol and procedures for the planned duration of participation
- •Maintenance Therapy Period (Period 2)
- •Registered objective response (stable disease or partial/complete response according to RECIST 1.1 criteria) to the therapy administered during the main study period
- •Ability and willingness to provide written informed consent for participation in Period 2
- •Karnofsky performance status ≥ 70%
- •Laboratory values within the following limits (per local lab normal ranges):
- •Hemoglobin ≥ 90 g/L
- •Leukocytes ≥ 3.0 × 10^9/L
- •Neutrophils ≥ 1.5 × 10^9/L
- •Platelets ≥ 100 × 10^9/L
- •Total bilirubin ≤ 2 × ULN (upper limit of normal)
- •AST ≤ 3 × ULN
- •ALT ≤ 3 × ULN
- •eGFR ≥ 60 mL/min
- •Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt
排除标准
- •Main Period (Period 1)
- •Prior therapy with cetuximab or other monoclonal antibody-based biologics
- •Chemotherapy, radiotherapy, or surgery for head and neck cancer within 3 months before screening
- •Any other surgery (except biopsy, implantable venous port placement, or urgent non-cancer surgery) within 3 months before screening
- •Nasopharyngeal carcinoma
- •Other malignancy within the past 5 years or prior/concurrent squamous cell carcinoma (except cured in situ ductal carcinoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer)
- •Expected survival < 3 months
- •Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
- •Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
- •Active infection requiring systemic antibiotic therapy
- •Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol within 6 months prior to screening or during the study
- •Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
- •Positive screening for HBsAg, anti-HCV, anti-HIV1/2 antibodies, or syphilis within 3 months prior to screening
- •Conditions preventing compliance with the study protocol per investigator
- •Participation in another investigational drug study within 6 months prior to screening
- •Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
- •Known hypersensitivity to any component of study therapy or combination chemotherapy drugs
- •Excessive alcohol use (>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits
- •Maintenance Therapy Period (Period 2)
- •Absence of a confirmed objective response to the administered therapy during the main study period, defined as failure to achieve disease stabilization or a partial/complete response according to RECIST v1.1
- •Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
- •Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
- •Active infection requiring systemic antibiotics
- •Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol for Period 2
- •Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
- •Conditions preventing compliance with study procedures per investigator
- •Participation in another investigational drug study
- •Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
- •Excessive alcohol use (>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits
研究组 & 干预措施
RPH-002 + docetaxel + cisplatin
Patients receive RPH-002 in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and RPH-002 monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: RPH-002 (Drug)
RPH-002 + docetaxel + cisplatin
Patients receive RPH-002 in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and RPH-002 monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: Cisplatin (Drug)
RPH-002 + docetaxel + cisplatin
Patients receive RPH-002 in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and RPH-002 monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: Docetaxel (Drug)
Erbitux® + docetaxel + cisplatin
Patients receive Erbitux® in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and Erbitux® monotherapy during the Maintenance Period (up to 8 weeks), or until disease progression or unacceptable toxicity
Patients who received therapy with Erbitux® during the Main Period will be switched to therapy with RPH-002 starting from Week 9 of the Maintenance Period
干预措施: Erbitux® (Drug)
Erbitux® + docetaxel + cisplatin
Patients receive Erbitux® in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and Erbitux® monotherapy during the Maintenance Period (up to 8 weeks), or until disease progression or unacceptable toxicity
Patients who received therapy with Erbitux® during the Main Period will be switched to therapy with RPH-002 starting from Week 9 of the Maintenance Period
干预措施: Cisplatin (Drug)
Erbitux® + docetaxel + cisplatin
Patients receive Erbitux® in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and Erbitux® monotherapy during the Maintenance Period (up to 8 weeks), or until disease progression or unacceptable toxicity
Patients who received therapy with Erbitux® during the Main Period will be switched to therapy with RPH-002 starting from Week 9 of the Maintenance Period
干预措施: Docetaxel (Drug)
结局指标
主要结局
Objective response rate (%) (ORR)
时间窗: At Visits 6 (Day 36), 12 (Day 78), and 18 (Day 120)
Objective response rate (%) (ORR) for a period of up to 18 weeks of therapy inclusive The objective response rate (ORR) is defined as the percentage of patients in each treatment group who achieve a complete or partial tumor response to therapy according to RECIST 1.1 criteria: * Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be \<10 mm * Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements
次要结局
- Disease Control Rate (%) (DCR; CR + PR + SD)(At Visits 6 (Day 36), 12 (Day 78), and 18 (Day 120))
- Proportion of patients (%) with adverse drug reactions (ADRs) of any severity(Up to Day 365)
- Proportion of patients (%) with adverse events (AEs) of any severity(Up to Day 365)
- Proportion of patients (%) with AEs of severity grade ≥ 3(Up to Day 365)
- Proportion of patients (%) with ADRs of severity grade ≥ 3(Up to Day 365)
- Proportion of patients (%) with serious adverse events (SAEs)(Up to Day 365)
- Proportion of patients (%) with serious adverse drug reactions (SADRs)(Up to Day 365)
- Proportion of patients (%) who required discontinuation of treatment due to development of ADRs/SADRs(Up to Day 365)
- Proportion of patients (%) who developed anti-drug antibodies (ADA) to cetuximab(Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36)
- Proportion of patients (%) who developed neutralizing antibodies (NAb) to cetuximab(Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36)