Study of Magrolimab Given Together With FOLFIRI/Bevacizumab (BEV) in Participants With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC) (ELEVATE CRC)

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)

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).

Study Overview

• Status: Terminated
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Magrolimab; Drug: Bevacizumab; Drug: Irinotecan; Drug: Fluorouracil; Drug: Leucovorin

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Westmead Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • Kinghorn Cancer Centre
    • Miranda, New South Wales, Australia, 2228
      • Southside Cancer Care Centre
    • St Leonards, New South Wales, Australia, 2065
      • Genesis Care North Shore
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Belgium
  • Haine-Saint-Paul, Belgium, 7100
    • Hopital de Jolimont
  • Libramont-Chevigny, Belgium, 6800
    • Centre Hospitalizer De L'Ardenne
• Canada
  • Ottawa, Canada, K1H 8L6
    • The Ottawa Hospital Cancer Centre
  • Toronto, Canada, M5G 1X6
    • Princess Margaret Cancer Centre
• France
  • Besançon, France, 25030
    • Centre Hospitalier Regional Universitaire Hopital Besancon
  • Lyon, France, 69008
    • Centre Léon Bérard - Centre de Lutte contre le Cancer
  • Paris, France, 75012
    • Hopital franco brittanique
  • Tours, France, 37000
    • CHU de Tours
• Germany
  • Dresden, Germany, 01307
    • Carl Gustav Carus Management GMBH
  • Munchen, Germany, 81675
    • Klinikum rechts der Isar der TU Munchen Zentrum fur klinische Studien der Klinik und Poliklinik fur Innere Medizin III
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Hong Kong Integrated Oncology Centre
• Italy
  • Meldola, Italy, 47014
    • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - Medical Oncology Department
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto (IOV)- IRCCS
  • Pisa, Italy, 56126
    • Azienda Ospedaliera Universitaria Pisana- UO Oncologia Medica
  • San Giovanni Rotondo, Italy, 71013
    • Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Clinico Humanitas
  • Vicenza, Italy, 36100
    • San Bortolo General Hospital- Oncology Department
• Puerto Rico
  • San Juan, Puerto Rico, 00902
    • Pan American Center for Oncology Trials, LLC
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • L'Hospitalet de Llobregat, Spain, 8908
    • Institut Català d'Oncologia- Hospital Duran I Reynals
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28050
    • Hospital HM Sanchinarro
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope ( City of Hope National Medical Center, City of Hope Medical Center )
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Center
    • Redondo Beach, California, United States, 90277
      • Torrance Memorial Physician Network
    • Santa Monica, California, United States, 90095
      • University of California Los Angeles (UCLA)
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology, Inc.
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York, PC
    • Rochester, New York, United States, 14642
      • AdventHealth
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Pennsylvania Hospital
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 327203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Medical Center
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Virginia Cancer Specialists, PC
  • Washington
    • Seattle, Washington, United States, 98103
      • Seattle Cancer Care Alliance (SCCA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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-fluorouracil (5-FU) or capecitabine with oxaliplatin and either bevacizumab, or for individuals with rat sarcoma (RAS) wild-type and left-sided tumors, bevacizumab, cetuximab, or panitumumab.
• Measurable disease (Response Evaluation Criteria in Solid Tumors (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 gene mutation (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 (Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0).
• Known dihydropyrimidine dehydrogenase deficiency.
• Acute intestinal obstruction or sub-obstruction, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI; Participants will receive magrolimab + bevacizumab + FOLFIRI as mentioned below: Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, every week (QW) beginning at Day 8 and for the next 6 doses (Cycle 1 Days 8, 15, and 22, and Cycle 2 Days 1, 8, 15, and 22); 30 mg/kg, every 2 weeks (Q2W) beginning 1 week after the last weekly 30 mg/kg dose (starting Cycle 3 Day 1 onwards) for every 28-day cycle.; Bevacizumab: 5 mg/kg, Q2W (Days 1 and 15) of every 28-day cycle.; FOLFIRI (Irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 IV bolus on first day, followed by 2400 mg/m^2 over the next 46 hours, Q2W (Days 1 and 15) of every 28-day cycle.	Drug: Magrolimab; Administered intravenous infusion; Other Names: GS-4721; Drug: Bevacizumab; Administered intravenous infusion; Drug: Irinotecan; Administered intravenous infusion; Other Names: CAMPTOSAR®; Drug: Fluorouracil; Administered intravenous infusion; Drug: Leucovorin; Administered intravenous infusion
Experimental: Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI; Participants will receive magrolimab + bevacizumab + FOLFIRI as mentioned below: Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, QW beginning at Day 8 and for the next 6 doses (Cycle 1 Days 8, 15, and 22, and Cycle 2 Days 1, 8, 15, and 22); 30 mg/kg, Q2W beginning 1 week after the last weekly 30 mg/kg dose (starting Cycle 3 Day 1 onwards) for every 28-day cycle.; Bevacizumab: 5 mg/kg, Q2W (Days 1 and 15) of every 28-day cycle.; FOLFIRI (Irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 IV bolus on first day, followed by 2400 mg/m^2 over the next 46 hours, Q2W (Days 1 and 15) of every 28-day cycle.	Drug: Magrolimab; Administered intravenous infusion; Other Names: GS-4721; Drug: Bevacizumab; Administered intravenous infusion; Drug: Irinotecan; Administered intravenous infusion; Other Names: CAMPTOSAR®; Drug: Fluorouracil; Administered intravenous infusion; Drug: Leucovorin; Administered intravenous infusion
Active Comparator: Randomized Cohort: Bevacizumab + FOLFIRI; Participants will receive bevacizumab + FOLFIRI as mentioned below: Bevacizumab: 5 mg/kg, Q2W (Days 1 and 15) of every 28-day cycle.; FOLFIRI (Irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 IV bolus on first day, followed by 2400 mg/m^2 over the next 46 hours, Q2W (Days 1 and 15) of every 28-day cycle.	Drug: Bevacizumab; Administered intravenous infusion; Drug: Irinotecan; Administered intravenous infusion; Other Names: CAMPTOSAR®; Drug: Fluorouracil; Administered intravenous infusion; Drug: Leucovorin; Administered intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-in Cohort: Number of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	DLT was defined as any,; Grade 3 or higher hematologic toxicity including, serious hemolytic anemia, grade 4 neutropenia lasting > 7 days; An event meeting Hy's Law criteria:Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation (≥ 3 x ULN) and,Treatment-emergent total bilirubin elevation (> 2 x ULN), and absence of cholestasis (defined as alkaline phosphatase < 2 x ULN), andNo other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, alcohol ingestion, congestive heart failure, worsening liver metastases, hemolysis)); Grade 3 or higher nonhematologic toxicity that has worsened in severity from pretreatment baseline during the DLT-assessment period; Grade 3 fatigue lasting > 7 days; In the opinion of the investigator, the AE was at least possibly related to magrolimab	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	Treatment-emergent adverse events (TEAEs) were defined as any AE that begun on or after the date of first dose of study drug up to the date of last dose of study treatment plus 30 days or the day before initiation of subsequent anticancer therapy, whichever came first. An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily have a causal relationship with the treatment.	First dose date up to last dose date (up to 36 weeks) plus 30 days
Safety Run-in Cohort: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0	Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade after the date of first dose of study drug up to the date of last dose of study treatment plus 30 days or the day before initiation of subsequent anticancer therapy, whichever came first.	First dose date up to last dose date (up to 36 weeks) plus 30 days
Randomized Cohort: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	PFS was defined as the time from the date of randomization until the earliest date of documented disease progression (PD) as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1), or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (KM) estimates were used in outcome measure analysis.	Up to 83.4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment Using RECIST Version 1.1	ORR was defined as the percentage of participants who achieve complete response (CR) or partial response (PR) that was confirmed at least 4 weeks after initial documentation of response, as determined by investigator assessment per RECIST, Version 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off.	Up to 83.4 weeks
Randomized Cohort: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1	DOR was defined as time from first documentation of CR or PR to the earliest date of documented disease progression as determined by investigator assessment, per RECIST V1.1, or death from any cause, whichever occurred first. PD was defined in outcome measure #4. CR and PR were defined in outcome measure #5. KM estimates were used in outcome measure analysis.	Up to 83.4 weeks
Randomized Cohort: Overall Survival (OS)	OS was defined as time from date of randomization to death from any cause. KM estimates were used in outcome measure analysis.	Up to 83.4 weeks
Randomized Cohort: Change From Baseline of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ) - Core Questionnaire EORTC-QLQ-C30 Score	EORTC QLQ-C30 is a quality of life (QOL) questionnaire for cancer participants, that has 30 items. 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, loss of appetite, constipation, diarrhea, and financial difficulties). Scoring of the QLQ-C30 was performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicated a higher level of symptoms (i.e. a worse state of the participant).	Baseline, Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle was of 28 days)
Randomized Cohort: Number of Participants With 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L) Score	EQ-5D-5L was an instrument for use as a measure of health outcome. The EQ-5D-5L consisted of 2 sections: EuroQoL (5 dimensions) (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ-VAS). EQ-5D comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Number of participants per category were reported.	Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle is of 28 days)
Randomized Cohort: Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score	The EQ-VAS recorded the participants' self-rated health on a vertical VAS, where the end points were labeled "the best health you can imagine" and "the worst health you can imagine." The scale range from 0 to 100, where '100' rating denotes the best health and '0' rating denotes the worst health. The EQ-VAS is used as a quantitative measure of health outcome that reflects the participants' own judgment.	Baseline, Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle is of 28 days)
Randomized Cohort: Change From Baseline of the Functional Assessment of Cancer Therapy (FACT) Colorectal Symptom Index (FCSI) Score	The FCSI was a set of brief, clinically relevant, colorectal cancer symptoms for assessing symptomatic response. It comprised the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions were combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items were scored from "0" to "4" representing "Not at All" through to "Very Much True". The raw score for all items was transformed to a 0-100 scale, and the average for each of the 3 subscales was calculated; high scores illustrated an improved state.	Baseline, Day 1 of Cycles 2, 3, 4 and last cycle (Cycle 8) (Each cycle is of 28 days)
Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time		Predose: Day 15, 29, 57, 113 and 169; Postdose: Day 57 (1 hour)
Safety Run-in and Randomized Cohorts: Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab		Up to 36 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Fakih MG, Tejani M, Ren X, Landes D, Werneke S, Curtis KK et al. 439TiP A phase II (ph2), randomized study of magrolimab with bevacizumab and FOLFIRI in previously treated patients with advanced inoperable metastatic colorectal cancer (mCRC). Annals of Oncology 2022; 33(7):S735.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2022
• Primary Completion (Actual): June 26, 2024
• Study Completion (Actual): June 26, 2024

Study Registration Dates

• First Submitted: April 8, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antidotes; Vitamin B Complex; Vitamins; Bevacizumab; Irinotecan; Magrolimab; Fluorouracil; Leucovorin
• Other Study ID Numbers: GS-US-587-6156; 2022-500177-13 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No