A Phase 2, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Bevacizumab and FOLFIRI Versus Bevacizumab and FOLFIRI in Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 18
- 主要终点
- Safety Run-in Cohort: • Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [ Time Frame: First dose date up to 28 days ]
研究概览
简要总结
The primary objectives of this study are: Safety run-in cohort: to evaluate safety and tolerability, and the recommended Phase 2 dose (RP2D) and (randomized cohort) to evaluate the efficacy of magrolimab in combination with bevacizumab and 5-fluorouracil, irinotecan, and leucovorin (FOLFIRI) in previously treated participants with advanced inoperable metastatic colorectal cancer (mCRC). Randomized Cohort: To evaluate the efficacy of magrolimab in combination with bevacizumab and FOLFIRI in mCRC as determined by progression-free survival (PFS) by investigator assessment
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Previously treated individuals with inoperable metastatic colorectal cancer (mCRC) who are ineligible for checkpoint inhibitor therapy (microsatellite instability (MSI)-H or mismatch repair deficient (dMMR) and are excluded).
- •Histologically or cytologically confirmed adenocarcinoma originating in the colon or rectum (excluding appendiceal and anal canal cancers) who have progressed on or after 1 prior systemic therapy in the setting where curative resection is not indicated. This therapy must have included chemotherapy based on 5-FU or capecitabine with oxaliplatin and either bevacizumab, or for patients with RAS wild-type and left-sided tumors, bevacizumab, cetuximab, or panitumumab.
- •Measurable disease (RECIST V1.1 criteria)
- •Individuals must have an eastern cooperative oncology group (ECOG) performance status of 0 or
- •Life expectancy of at least 12 weeks.
- •Laboratory measurements, blood counts: adequate hemoglobin, neutrophil, and platelet counts
- •Adequate liver function
- •Adequate renal function
- •Note: Other protocol defined Inclusion criteria may apply
排除标准
- •Prior anticancer therapy including chemotherapy, hormonal therapy, or investigational agents within 3 weeks or within at least 4 half-lives prior to magrolimab dosing (up to a maximum of 4 weeks), whichever is shorter.
- •Known dihydropyrimidine dehydrogenase deficiency.
- •History of abdominal fistulas, trachea-oesophageal fistulas, any other Grade 4 gastrointestinal perforations, nongastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening.
- •Acute intestinal obstruction or subobstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colonic prosthesis.
- •Unhealed wound, active gastric or duodenal ulcer, or bone fracture.
- •Note: Other protocol defined Exclusion criteria may apply.
- •Uncontrolled arterial hypertension.
- •Thromboembolic event in the 6 months before inclusion (eg, transitory ischemic stroke, stroke, subarachnoid hemorrhage) except peripheral deep vein thrombosis treated with anticoagulants.
- •Active central nervous system (CNS) disease. Individuals with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids for at least 4 weeks) are allowed.
- •Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening.
- •History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
- •Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study.
- •Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
- •Known inherited or acquired bleeding disorders.
- •Second malignancy, except treated basal cell or localized squamous skin carcinomas, or localized prostate cancer
- •Known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E or MSI-H mutations or dMMR.
- •Uncontrolled pleural effusion.
- •Persistent Grade 2 or more gastrointestinal bleeding.
- •Individuals with prior irinotecan therapy.
- •Clinically significant coronary artery disease or myocardial infarction within 6 months prior to inclusion.
- •Peripheral neuropathy of more than Grade 2 (CTCAE Version 5.0).
研究组 & 干预措施
-
Participants receiving -
干预措施: - (Drug)
结局指标
主要结局
Safety Run-in Cohort: • Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [ Time Frame: First dose date up to 28 days ]
Safety Run-in Cohort: • Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [ Time Frame: First dose date up to 28 days ]
Safety Run-in Cohort: • Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0 [ Time Frame: First dose date up to 3 years ] • Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0 [ Time Frame: First dose date up to 3 years ]
Safety Run-in Cohort: • Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0 [ Time Frame: First dose date up to 3 years ] • Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0 [ Time Frame: First dose date up to 3 years ]
Randomized Cohort: • Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Up to 3 years ] PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, or death from any cause, whichever occurs first.
Randomized Cohort: • Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Up to 3 years ] PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, or death from any cause, whichever occurs first.
次要结局
未报告次要终点
研究者
EU Clinical Trials Support
Scientific
Gilead Sciences International Limited