Study of Magrolimab Given Together With FOLFIRI/BEV in Patients With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC) (ELEVATE CRC)
Metastatic Colorectal Cancer
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
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 with oxaliplatin and either bevacizumab, or for patients with RAS wild-type and left-sided tumors, bevacizumab or 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 1 (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.
Sites / Locations
- City of Hope ( City of Hope National Medical Center, City of Hope Medical Center )Recruiting
- USC Norris Comprehensive Cancer CenterRecruiting
- Stanford Cancer CenterRecruiting
- Torrance Memorial Physician NetworkRecruiting
- University of California Los Angeles (UCLA)Recruiting
- Orlando Health Cancer InstituteRecruiting
- Fort Wayne Medical Oncology and Hematology, Inc.Recruiting
- University of KansasRecruiting
- University of MichiganRecruiting
- Roswell Park Cancer InstituteRecruiting
- Hematology Oncology Associates of Central New York, PCRecruiting
- AdventHealthRecruiting
- Pennsylvania HospitalRecruiting
- Fox Chase Cancer CenterRecruiting
- Avera Cancer InstituteRecruiting
- Sarah Cannon Research InstituteRecruiting
- Texas OncologyRecruiting
- Baylor College of Medicine Medical CenterRecruiting
- Virginia Cancer Specialists, PCRecruiting
- Seattle Cancer Care Alliance (SCCA)Recruiting
- Westmead HospitalRecruiting
- Kinghorn Cancer CentreRecruiting
- Southside Cancer Care CentreRecruiting
- Genesis Care North ShoreRecruiting
- Princess Alexandra HospitalRecruiting
- Flinders Medical CentreRecruiting
- Austin HealthRecruiting
- The Alfred HospitalRecruiting
- Hôpital de JolimontRecruiting
- Centre Hospitalizer De L'ArdenneRecruiting
- Princess Margaret Cancer CentreRecruiting
- Centre Hospitalier Regional Universitaire Hopital BesanconRecruiting
- Centre Léon Bérard - Centre de Lutte contre le CancerRecruiting
- Hopital franco brittaniqueRecruiting
- CHU de ToursRecruiting
- Carl Gustav Carus Management GMBHRecruiting
- Klinikum rechts der Isar der TU Munchen Zentrum fur klinische Studien der Klinik und Poliklinik fur Innere Medizin IIIRecruiting
- Hong Kong Integrated Oncology CentreRecruiting
- Hong Kong United Oncology Center
- Queen Mary HospitalRecruiting
- Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - Medical Oncology DepartmentRecruiting
- Istituto Oncologico Veneto (IOV)- IRCCSRecruiting
- Azienda Ospedaliera Universitaria Pisana- UO Oncologia MedicaRecruiting
- Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Clinico HumanitasRecruiting
- San Bortolo General Hospital- Oncology DepartmentRecruiting
- Pan American Center for Oncology Trials, LLCRecruiting
- Hospital Universitari Vall d'HebronRecruiting
- Institut Català d'Oncologia- Hospital Duran I ReynalsRecruiting
- Hospital General Universitario Gregorio MarañónRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- Hospital HM SanchinarroRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI
Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI
Randomized Cohort: Bevacizumab + FOLFIRI
Participants will receive magrolimab in de-escalating doses to establish recommended Phase 2 dose (RP2D) in combination with + bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).
Participants will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).
Participants will receive bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).