Efficacy and Safety of Retlirafusp Alfa Plus Bevacizumab and Chemotherapy With or Without Short-Course Radiotherapy in Patients With Colorectal Cancer Liver Metastases: a Randomized Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Progression-Free Survival
研究概览
简要总结
Efficacy and safety of retlirafusp alfa combined with bevacizumab and chemotherapy with or without short-course radiotherapy in conversion therapy for advanced colorectal cancer liver metastases: an exploratory study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Provide signed written informed consent and voluntarily agree to participate in this study.
- •Age ≥ 18 years and ≤ 75 years.
- •Histologically confirmed colorectal adenocarcinoma.
- •Liver metastasis confirmed by imaging or pathology.
- •Have not received any prior anti-cancer therapy.
- •At least one measurable lesion according to RECIST v1.
- •pMMR/MSS status confirmed by a local testing center, or unknown status.
- •Be able to swallow tablets.
- •ECOG PS 0-1
- •Have no contraindications for surgery.
- •Have adequate major organ function.
排除标准
- •Have a history of allergy to monoclonal antibodies, any component of retlirafusp alfa, bevacizumab, capecitabine, oxaliplatin, or other platinum-based agents.
- •Have previously received or are currently receiving any of the following treatments:
- •Any anti-tumor therapy including surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
- •Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes within 2 weeks prior to the first dose of study drug (at a dose > 10 mg/day prednisone or equivalent). Inhaled or topical corticosteroids, and adrenal replacement therapy at doses > 10 mg/day prednisone or equivalent, are permitted in the absence of active autoimmune disease.
- •Receipt of live attenuated vaccine within 4 weeks prior to the first dose of study drug.
- •Major surgery or severe trauma within 4 weeks prior to the first dose of study drug.
- •Have any active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism (patients on hormone replacement therapy may be considered for inclusion). Patients with psoriasis or childhood asthma/allergy that has completely resolved and requires no intervention in adulthood may be considered for inclusion, but those requiring medical intervention with bronchodilators are not eligible.
- •Have a history of immunodeficiency, including HIV-positive test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.
- •Have poorly controlled cardiac symptoms or diseases, including but not limited to: (1) heart failure of New York Heart Association (NYHA) class ≥ II; (2) unstable angina; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmias that have not been clinically intervened or remain poorly controlled after intervention.
- •Have experienced a severe infection (CTCAE grade > 2) within 4 weeks prior to the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; or have evidence of active pulmonary inflammation on baseline chest imaging, or have signs/symptoms of infection or require oral or intravenous antibiotic therapy within 14 days prior to the first dose of study drug (except for prophylactic antibiotic use).
- •Have active pulmonary tuberculosis infection by history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or a history of active pulmonary tuberculosis infection > 1 year ago without adequate treatment.
- •Have hepatitis B (HBV DNA ≥ 2000 IU/mL or ≥ 10⁴ copies/mL), or hepatitis C (positive anti-HCV antibody and HCV RNA above the lower limit of detection of the assay).
- •Have been diagnosed with another malignancy within 5 years prior to the first dose of study drug, except for malignancies with a low risk of metastasis or death (5-year survival rate > 90%), such as adequately treated basal cell carcinoma or squamous cell skin cancer, or cervical carcinoma in situ, which may be considered for inclusion.
- •Are pregnant or breastfeeding.
研究组 & 干预措施
SCRT combined with Retlirafusp Alfa Plus Bevacizumab and Chemotherapy
Total dose 25 Gy delivered in 5 fractions (5 Gy per fraction, once daily over 5 consecutive days). Retlirafusp alfa plus bevacizumab and capox will recive every 3 weeks, initiated 1 week after radiontherapy completion.
干预措施: CAPOX (Drug)
SCRT combined with Retlirafusp Alfa Plus Bevacizumab and Chemotherapy
Total dose 25 Gy delivered in 5 fractions (5 Gy per fraction, once daily over 5 consecutive days). Retlirafusp alfa plus bevacizumab and capox will recive every 3 weeks, initiated 1 week after radiontherapy completion.
干预措施: SCRT (Radiation)
SCRT combined with Retlirafusp Alfa Plus Bevacizumab and Chemotherapy
Total dose 25 Gy delivered in 5 fractions (5 Gy per fraction, once daily over 5 consecutive days). Retlirafusp alfa plus bevacizumab and capox will recive every 3 weeks, initiated 1 week after radiontherapy completion.
干预措施: Retlirafusp alfa Injection (Drug)
Retlirafusp Alfa combined with Bevacizumab and Chemotherapy
Retlirafusp alfa plus bevacizumab and capox will recive every 3 weeks
干预措施: Retlirafusp alfa Injection (Drug)
Retlirafusp Alfa combined with Bevacizumab and Chemotherapy
Retlirafusp alfa plus bevacizumab and capox will recive every 3 weeks
干预措施: CAPOX (Drug)
Retlirafusp Alfa combined with Bevacizumab and Chemotherapy
Retlirafusp alfa plus bevacizumab and capox will recive every 3 weeks
干预措施: Bevacizumab (Drug)
SCRT combined with Retlirafusp Alfa Plus Bevacizumab and Chemotherapy
Total dose 25 Gy delivered in 5 fractions (5 Gy per fraction, once daily over 5 consecutive days). Retlirafusp alfa plus bevacizumab and capox will recive every 3 weeks, initiated 1 week after radiontherapy completion.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Progression-Free Survival
时间窗: Each follow up visit, assessed up to 60 months
Assessed by the investigator using RECIST v1.1, defined as the time from the start of study treatment to disease progression, or relapse after resection of liver metastases, or death due to any cause.
次要结局
- Overall Response Rate(assessed up to 12 months)
- R0 Resection Rate(Each follow up visit, assessed up to 12 month)
- Pathological complete response rate (pCR)(2 years after last patient in study)
- Overall Survival(Each follow up visit, assessed up to 60 months)
- Toxicity (AE)(2 years after last patient in study)
研究者
Tao Zhang
MD
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology