Study of Magrolimab Given Together With FOLFIRI/BEV in Participants With Previously Treated 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).
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 with chemotherapy based on 5-fluorouracil (5-FU) with oxaliplatin and bevacizumab.
- 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.
- Individuals without prior bevacizumab therapy for colorectal cancer.
- 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 colic 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
- Known active or chronic hepatitis B or C infection or HIV infection in medical history.
- Uncontrolled pleural effusion.