study of magrolimab given together with folfiri/bev in patients with previously treated advanced inoperable metastatic colorectal cancer (mcrc)

Conditions: Metastatic Colorectal Cancer

Summary: the goals of this clinical study are to learn more about the safety, tolerability and effectiveness of magrolimab in combination with bevacizumab and 5-fluorouracil, irinotecan, and leucovorin (folfiri) in previously treated participants with advanced inoperable metastatic colorectal cancer (mcrc). 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).


Eligibility criteria:
key inclusion criteria: * 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 1. * life expectancy of at least 12 weeks. * laboratory measurements, blood counts: adequate hemoglobin, neutrophil, and platelet counts * adequate liver function. * adequate renal function. key exclusion criteria: * 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 v-raf murine sarcoma viral oncogene homolog b1 (braf) v600e or msi-h mutations or dmmr. * 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). * known dihydropyrimidine dehydrogenase deficiency. * 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. * history of abdominal fistulas, trachea-oesophageal fistulas, any other grade 4 gastrointestinal perforations, nongastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening. * 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. * known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient. * known inherited or acquired bleeding disorders. * 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. * second malignancy, except treated basal cell or localized squamous skin carcinomas, or localized prostate cancer. * uncontrolled pleural effusion. note: other protocol defined inclusion/exclusion criteria may apply.