Metastatic Colorectal CancerPhase 2ELEVATE CRCNCT05330429
Study of Magrolimab Given Together With FOLFIRI/Bevacizumab (BEV) in Participants With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC)
A Phase 2 study testing Magrolimab, Bevacizumab and Irinotecan in people with Metastatic Colorectal Cancer, run by Gilead Sciences at 51 sites in 10 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Magrolimab, Bevacizumab and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 51 sitesin 10 countries
- Study dates
- 8 Jul 2022to 26 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
51 sites in 10 countries.
51 sites in 10 countries
United States20 sites
University of Michigan
Ann Arbor, Michigan, 48106
Virginia Cancer Specialists, PC
Arlington, Virginia, 22205
Roswell Park Cancer Institute
Buffalo, New York, 14263
Texas Oncology
Dallas, Texas, 75246
City of Hope ( City of Hope National Medical Center, City of Hope Medical Center )
Duarte, California, 91010
Hematology Oncology Associates of Central New York, PC
East Syracuse, New York, 13057
Fort Wayne Medical Oncology and Hematology, Inc.
Fort Wayne, Indiana, 46845
Baylor College of Medicine Medical Center
Houston, Texas, 77030
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Sarah Cannon Research Institute
Nashville, Tennessee, 327203
Orlando Health Cancer Institute
Orlando, Florida, 32806
Stanford Cancer Center
Palo Alto, California, 94305
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Torrance Memorial Physician Network
Redondo Beach, California, 90277
AdventHealth
Rochester, New York, 14642
University of California Los Angeles (UCLA)
Santa Monica, California, 90095
Seattle Cancer Care Alliance (SCCA)
Seattle, Washington, 98103
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
University of Kansas
Westwood, Kansas, 66205
Australia8 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Westmead Hospital
Blacktown, New South Wales, 2148
Kinghorn Cancer Centre
Darlinghurst, New South Wales, 2010
Austin Health
Heidelberg, Victoria, 3084
The Alfred Hospital
Melbourne, Victoria, 3004
Southside Cancer Care Centre
Miranda, New South Wales, 2228
Genesis Care North Shore
St Leonards, New South Wales, 2065
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Italy5 sites
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - Medical Oncology Department
Meldola, 47014
Istituto Oncologico Veneto (IOV)- IRCCS
Padova, 35128
Azienda Ospedaliera Universitaria Pisana- UO Oncologia Medica
Pisa, 56126
Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Clinico Humanitas
San Giovanni Rotondo, 71013
San Bortolo General Hospital- Oncology Department
Vicenza, 36100
Spain5 sites
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Institut Català d'Oncologia- Hospital Duran I Reynals
L'Hospitalet de Llobregat, 8908
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital HM Sanchinarro
Madrid, 28050
France4 sites
Centre Hospitalier Regional Universitaire Hopital Besancon
Besançon, 25030
Centre Léon Bérard - Centre de Lutte contre le Cancer
Lyon, 69008
Hopital franco brittanique
Paris, 75012
CHU de Tours
Tours, 37000
Belgium2 sites
Hôpital de Jolimont
Haine-Saint-Paul, 7100
Centre Hospitalizer De L'Ardenne
Libramont-Chevigny, 6800
Canada2 sites
The Ottawa Hospital Cancer Centre
Ottawa, K1H 8L6
Princess Margaret Cancer Centre
Toronto, M5G 1X6
Germany2 sites
Carl Gustav Carus Management GMBH
Dresden, 01307
Klinikum rechts der Isar der TU Munchen Zentrum fur klinische Studien der Klinik und Poliklinik fur Innere Medizin III
München, 81675
Hong Kong2 sites
Hong Kong Integrated Oncology Centre
Hong Kong, 0
Queen Mary Hospital
Hong Kong
Puerto Rico1 site
Pan American Center for Oncology Trials, LLC
San Juan, PR, 00902
About this study
Official title: 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).
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Magrolimab, Bevacizumab, Irinotecan, Fluorouracil, Leucovorin
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MagrolimabDrug
Also called GS-4721
Administered intravenous infusion
BevacizumabDrug
Administered intravenous infusion
IrinotecanDrug
Also called CAMPTOSAR®
Administered intravenous infusion
FluorouracilDrug
Administered intravenous infusion
LeucovorinDrug
Administered intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI | Experimental | 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. Receives: Drug: Magrolimab; Drug: Bevacizumab; Drug: Irinotecan; Drug: Fluorouracil; Drug: Leucovorin |
| Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI | Experimental | 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. Receives: Drug: Magrolimab; Drug: Bevacizumab; Drug: Irinotecan; Drug: Fluorouracil; Drug: Leucovorin |
| Randomized Cohort: Bevacizumab + FOLFIRI | Active comparator | 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. Receives: Drug: Bevacizumab; Drug: Irinotecan; Drug: Fluorouracil; Drug: Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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), and
- No 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 83.4 weeks
Secondary outcomes (9)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Up to 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2022
- Study start8 Jul 2022
- Primary completion26 Jun 2024
- Study completion26 Jun 2024
Why it stopped: Sponsor decision to terminate study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05330429
- Sponsor's protocol ID
- GS-US-587-6156
- Other IDs
- 2022-500177-13
- Acronym
- ELEVATE CRC
- Status last verified
- Jun 2025
- First submitted
- 8 Apr 2022
- Last updated
- 1 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05330429
- Acronym / sponsor ID
- ELEVATE CRC / GS-US-587-6156
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision to terminate study
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 8 Jul 2022 (actual)
- Primary completion
- 26 Jun 2024 (actual)
- Study completion
- 26 Jun 2024 (actual)
- First posted
- 15 Apr 2022 (actual)
- Results
- Posted 1 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI | Experimental | Drug: Magrolimab, Drug: Bevacizumab, Drug: Irinotecan, Drug: Fluorouracil, Drug: LeucovorinParticipants 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. |
| Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI | Experimental | Drug: Magrolimab, Drug: Bevacizumab, Drug: Irinotecan, Drug: Fluorouracil, Drug: LeucovorinParticipants 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. |
| Randomized Cohort: Bevacizumab + FOLFIRI | Active comparator | Drug: Bevacizumab, Drug: Irinotecan, Drug: Fluorouracil, Drug: LeucovorinParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MagrolimabAlso: GS-4721Administered intravenous infusion | Drug | Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI, Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI |
| BevacizumabAdministered intravenous infusion | Drug | Randomized Cohort: Bevacizumab + FOLFIRI, Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI, Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI |
| IrinotecanAlso: CAMPTOSAR®Administered intravenous infusion | Drug | Randomized Cohort: Bevacizumab + FOLFIRI, Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI, Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI |
| FluorouracilAdministered intravenous infusion | Drug | Randomized Cohort: Bevacizumab + FOLFIRI, Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI, Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI |
| LeucovorinAdministered intravenous infusion | Drug | Randomized Cohort: Bevacizumab + FOLFIRI, Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI, Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI |
Primary outcome
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
Time frame: First dose date up to 28 days
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), and * No 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
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 last dose date (up to 36 weeks) plus 30 days
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.
Safety Run-in Cohort: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0
Time frame: First dose date up to last dose date (up to 36 weeks) plus 30 days
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.
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 83.4 weeks
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.
9 secondary outcomes
Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment Using RECIST Version 1.1
Time frame: Up to 83.4 weeks
Randomized Cohort: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1
Time frame: Up to 83.4 weeks
Randomized Cohort: Overall Survival (OS)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 36 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundFakih 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.
- Gilead Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
51 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Magrolimab, Bevacizumab and Irinotecan in people with Metastatic Colorectal Cancer, run by Gilead Sciences at 51 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 51 sites in United States, Australia, Italy, Spain, France and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: First dose date up to 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05330429, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2025.