A Phase II, Multicenter, Open Label, Parallel Cohort Clinical Trial to Evaluate the Efficacy and Safety of PM8002 (BNT327) in Combination With Chemotherapy in First Line MSS or MSI-L/pMMR Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 11
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
PM8002 (BNT327) is a bispecific antibody targeting PD-L1 and VEGF. This is a phase II trial to evaluate the efficacy and safety of PM8002 in combination with chemotherapy in first line MSS or MSI-L/pMMR metastatic colorectal cancer.
详细描述
A multicenter, randomized, open-label study design is used, with a planned enrollment of 100 participants, 40 in the PM8002 (BNT327)+ chemotherapy regimen 1 group, 30 in the PM8002 (BNT327)+ chemotherapy regimen 2 group and 30 in the PM8002 (BNT327)+ chemotherapy regimen 3 group. The investigators make the decision on which chemotherapy regimen to be used in the participants. After combined chemotherapy regimen is confirmed, participants will be randomized to one of two dose levels of PM8002(BNT327) plus chemotherapy.
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
- •Signed informed consent form before any trial-related processes.
- •Age ≥ 18 years male or female.
- •Histologically or cytologically confirmed metastatic colorectal cancer (stage IV, UICC/AJCC staging system) that is not suitable for or cannot be radically resected surgically.
- •Participants must not have dMMR or MSI-H.
- •No prior systemic anti-tumor therapy for metastatic colorectal cancer.
- •have adequate organ function.
- •The investigator confirms at least one measurable lesion according to RECIST v1.
- •A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if progression is confirmed.
- •The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or
排除标准
- •Received the following treatments or medications prior to starting study treatment:
- •Received palliative local therapy, non-specific immunomodulatory therapy, or chineses herbal therapy with an anti-tumor indication within 14 days prior to study treatment.
- •Treatment with systemic glucocorticoids (prednisone >10 mg/day or equivalent dose of other glucocorticoids) or other immunosuppressive agents within 14 days prior to initiation of study treatment. Note: treatment with local, intraocular, intra-articular, intranasal, and inhaled glucocorticosteroids and short-term prophylactic use of glucocorticoids (e.g., to prevent allergy to contrast agent) are allowed.
- •Have a major coagulation disorder or other evidence of significant bleeding risk.
- •Adverse effects of prior antitumor therapy have not returned to a CTCAE 5.0 grade rating of ≤ grade 1
- •Have a serious non-healing wound, ulcer, or bone fracture.
- •History of abdominal fistula, gastrointestinal perforation, or abdominal abscess, history of gastrointestinal obstruction, or clinical signs of gastrointestinal obstruction within 6 months prior to initiation of study treatment.
- •Severe uncontrollable intra-abdominal inflammation that requires clinical intervention, in the judgment of the investigator.
- •Have uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment.
研究组 & 干预措施
Chemotherapy regimen 1 group - PM8002 Dose 1 + chemotherapy regimen 1
Subjects will be administered with PM8002 (Dose 1) plus chemotherapy regimen 1 via intravenously (IV) Q2W until progression.
干预措施: PM8002 (Drug)
Chemotherapy regimen 1 group - PM8002 Dose 2 + chemotherapy regimen 1
Subjects will be administered with PM8002 (Dose 2) plus chemotherapy regimen 1 via intravenously (IV) Q2W until progression.
干预措施: PM8002 (Drug)
Chemotherapy regimen 2 group - PM8002 Dose 1 + chemotherapy regimen 2
Subjects will be administered with PM8002 (Dose 1) plus chemotherapy regimen 2 via intravenously (IV) and oral administration (PO) Q3W until progression.
干预措施: PM8002 (Drug)
Chemotherapy regimen 2 group - PM8002 Dose 2 + chemotherapy regimen 2
Subjects will be administered with PM8002 (Dose 2) plus chemotherapy regimen 2 via intravenously (IV) and oral administration (PO) Q3W until progression.
干预措施: PM8002 (Drug)
Chemotherapy regimen 1 group - PM8002 Dose 1 + chemotherapy regimen 1
Subjects will be administered with PM8002 (Dose 1) plus chemotherapy regimen 1 via intravenously (IV) Q2W until progression.
干预措施: Chemotherapy Regimen 1 (Drug)
Chemotherapy regimen 1 group - PM8002 Dose 2 + chemotherapy regimen 1
Subjects will be administered with PM8002 (Dose 2) plus chemotherapy regimen 1 via intravenously (IV) Q2W until progression.
干预措施: Chemotherapy Regimen 1 (Drug)
Chemotherapy regimen 2 group - PM8002 Dose 1 + chemotherapy regimen 2
Subjects will be administered with PM8002 (Dose 1) plus chemotherapy regimen 2 via intravenously (IV) and oral administration (PO) Q3W until progression.
干预措施: Chemotherapy Regimen 2 (Drug)
Chemotherapy regimen 2 group - PM8002 Dose 2 + chemotherapy regimen 2
Subjects will be administered with PM8002 (Dose 2) plus chemotherapy regimen 2 via intravenously (IV) and oral administration (PO) Q3W until progression.
干预措施: Chemotherapy Regimen 2 (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to approximately 2 years
Objective response rate is the proportion of subjects with complete response (CR) or partial response (PR), based on RECIST v1.1.
Occurrence and severity of TEAE (treatment emergent adverse event), TRAE（treatment related adverse event）, TESAE (treatment emergent serious adverse event）, TRSAE (treatment related serious adverse event）
时间窗: From the first dose of the investigational medicinal product (IMP) to the 30-day Follow-Up Visit
AEs are graded according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0 in the combination treatment regimen.
Occurrence and severity of TEAE (treatment emergent adverse event), TRAE（treatment related adverse event）, TESAE (treatment emergent serious adverse event）, TRSAE (treatment related serious adverse event）
时间窗: From the first dose of the investigational medicinal product (IMP) to the 30-day Safety Follow-Up Visit
AEs are graded according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0 in the combination treatment regimen.
次要结局
- Progression free survival (PFS)(Up to approximately 2 years)
- Duration of response (DoR)(Up to approximately 2 years)
- Disease control rate (DCR)(Up to approximately 2 years)
- Time to response (TTR)(Up to approximately 2 years)
- Overall survival (OS)(Up to approximately 5 years)