NCT07796763尚未招募2 期
A Global, Multicenter, Randomized, Dose-Optimization Phase II Study of Trastuzumab Rezetecan (SHR-A1811) in Combination With mFOLFOX6 (-1) and Bevacizumab as First-Line Treatment in Patients With HER2-Positive Advanced Colorectal Cancer (HORIZON-CRC221)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
This global study is being conducted to evaluate the safety and determine the recommended phase 3 dose of trastuzumab rezetecan in combination with mFOLFOX6 chemotherapy (dose level -1) and bevacizumab as first-line treatment in participants with advanced colorectal cancer that expresses HER2, including but not limited to HER2 immunohistochemistry (IHC) 2+ "equivocal" or 3+ "positive" based on gastric cancer criteria, focused on the Western population. Encouraging data in efficacy and safety with trastuzumab rezetecan in a similar setting in China (NCT06015048) were presented at 2026 American Society of Clinical Oncology annual meeting.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG performance status score of 0 or
- •Histologically or cytologically confirmed unresectable, recurrent, or metastatic colorectal adenocarcinoma that is HER2-positive. "HER2-positive" indicates IHC 2+ or 3+, or HER2 (ERBB2) amplification by NGS at a CLIA-certified or ISO-accredited laboratory. HER2 IHC 2+/3+ should be based on gastric cancer criteria.
- •Either have not received any prior systemic anti-tumor therapy (including, but not limited to, systemic chemotherapy, molecular targeted drug therapy, immunotherapy, biotherapy, or other investigational agents), or, if previously treated with neoadjuvant or adjuvant therapy, have first documented recurrence or metastasis >6 months after the last dose of neoadjuvant or adjuvant therapy. Participants known to have dMMR or high-level MSI-H are excluded unless the investigator determines they are unsuitable for anti-PD-1/PD-L1 therapy. Participants known to have BRAF V600 mutation are excluded unless the investigator determines they are unsuitable for BRAF-targeting therapy. Note that participants may have received a maximum of 2 doses of mFOLFOX6 with or without bevacizumab in the locally advanced/unresectable or metastatic setting prior to randomization.
- •Have at least one measurable lesion according to the RECIST version 1.
- •Measurable lesions should not have received prior local therapy such as radiotherapy (lesions located within a previous radiotherapy field can be considered as target lesions if progression is confirmed).
排除标准
- •Prior Treatments:
- •Prior treatment with anti-HER2 ADCs featuring exatecan or its derivatives as the payload (a topoisomerase I inhibitor), such as trastuzumab deruxtecan (Enhertu®, DS-8201a).
- •Treatment with any investigational drug or therapy not yet approved for marketing within 4 weeks prior to the first dose of the IMP.
- •Systemic anti-tumor therapy within 4 weeks prior to the first dose of the IMP, including chemotherapy, biotherapy, targeted therapy, or immunotherapy. For small molecule targeted therapies, a washout period of at least 5 half-lives or 7 days (whichever is longer) from the last dose is required before the first dose of the IMP. Note that participants may have received a maximum of 2 doses of mFOLFOX6 with or without bevacizumab in the locally advanced/unresectable or metastatic setting prior to randomization.
- •Palliative radiotherapy completed within 2 weeks prior to the first dose of the IMP.
- •Major surgery within 4 weeks prior to the first dose of the IMP or planned elective surgery during the trial period. Minor traumatic procedures (e.g., needle biopsy, endoscopy, drainage) within 7 days prior. Presence of non-healed wounds (severe, non-healing, or dehisced) or untreated fractures.
- •Use of aspirin (>325 mg/day), dipyridamole, ticlopidine, clopidogrel, cilostazol, or other drugs known to inhibit platelet function within 1 week prior to the first dose of the IMP.
- •Administration of live attenuated vaccines within 4 weeks prior to the first dose of the IMP, or anticipated requirement for such vaccines during the study treatment period.
- •History of hypersensitivity to monoclonal antibodies, any component of the trastuzumab rezetecan formulation, fluorouracil, levo-leucovorin (or leucovorin), oxaliplatin, bevacizumab, or related drugs.
- •Presence of Grade >1 peripheral sensory neuropathy.
- •History of hemoptysis (approximately ≥2.5 mL of fresh blood in one episode) within 3 months prior to the first dose of the IMP.
- •Tumor encasement or invasion of major blood vessels (e.g., pulmonary artery, superior vena cava) as indicated by CT or MRI.
研究组 & 干预措施
Treatment group A
Experimental
Trastuzumab Rezetecan (SHR-A1811; high dose) in Combination with mFOLFOX6 (-1) and Bevacizumab injection
干预措施: Trastuzumab Rezetecan (SHR-A1811) injection; high dose (Drug)
Treatment group B
Experimental
Trastuzumab Rezetecan (SHR-A1811; low dose) in Combination with mFOLFOX6 (-1) and Bevacizumab injection.
干预措施: Trastuzumab Rezetecan (SHR-A1811) injection; low dose (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: about two years
Determination of the recommended phase 3 dose
时间窗: about two years
次要结局
- Progression free survival, as assessed by the investigator(about two years)
- Overall survival(about two years)
- Objective response rate, as assessed by the investigator(about two years)
- Disease control rate, as assessed by the investigator(about two years)
- Duration of response, as assessed by the investigator(about two years)
研究者
研究点 (1)
Loading locations...
相似试验
招募中
3 期
A Study to Compare the Efficacy and Safety of Oral Azacitidine (Oral-Aza, ONUREG®) plus BSC versus Placebo plus BSC in Participants with IPSS-R Low- or Intermediate-risk MDS2022-500479-29-00Celgene Corp.166
尚未招募
1 期
A Study of Subcutaneous FL115 Monotherapy in Participants With Advanced Solid TumorsAdvanced Solid TumoursNCT07785193Suzhou Forlong Biotechnology Co., Ltd29
招募中
1 期
A Study of Lutetium [177Lu]-BL-ARC001 in Patients With Locally Advanced or Metastatic Lung Cancer, Breast Cancer, Head and Neck Squamous Cell Carcinoma and Other Solid TumorsBreast CancerLung CancerNCT07274852Sichuan Baili Pharmaceutical Co., Ltd.22
招募中
1 期
AQUA07 in Patients With ALK-Positive Non-Small Cell Lung CancerNCT07617337Chugai Pharmaceutical102
招募中
1 期
A Study of [177Lu]Lu-A9-0631 and [225Ac]Ac-A9-0642 With [68Ga]Ga-A9-6217 or [177Lu]Lu-A9-0631 Imaging in GRPR+ Solid TumorsProstate CancerGRPR-positive Solid TumorsBreast CancerColorectal CancerNCT07661641Alpha-9 Oncology USA Inc.115