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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05330429




Registration number
NCT05330429
Ethics application status
Date submitted
8/04/2022
Date registered
15/04/2022
Date last updated
26/04/2024

Titles & IDs
Public title
Study of Magrolimab Given Together With FOLFIRI/BEV in Patients With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC)
Scientific 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)
Secondary ID [1] 0 0
2022-500177-13
Secondary ID [2] 0 0
GS-US-587-6156
Universal Trial Number (UTN)
Trial acronym
ELEVATE CRC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Magrolimab
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Irinotecan
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Leucovorin

Experimental: Safety Run-in Cohort: Magrolimab + 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).

Experimental: Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI - 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).

Active Comparator: Randomized Cohort: Bevacizumab + FOLFIRI - 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).


Treatment: Drugs: Magrolimab
Administered intravenously

Treatment: Drugs: Bevacizumab
Administered intravenously

Treatment: Drugs: Irinotecan
Administered intravenously

Treatment: Drugs: Fluorouracil
Administered intravenously

Treatment: Drugs: Leucovorin
Administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Run-in Cohort: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Timepoint [1] 0 0
First dose date up to 28 days
Primary outcome [2] 0 0
Safety Run-in Cohort: Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0
Timepoint [2] 0 0
First dose date up to 3 years
Primary outcome [3] 0 0
Safety Run-in Cohort: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0
Timepoint [3] 0 0
First dose date up to 3 years
Primary outcome [4] 0 0
Randomized Cohort: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment Using RECIST Version 1.1
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Randomized Cohort: Duration of Response (DOR) as Assessed by Investigator Assessment Per RECIST Version 1.1
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Randomized Cohort: Overall Survival (OS)
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Randomized Cohort: Change From Baseline of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire EORTC-QLQ-C30 Score
Timepoint [4] 0 0
Baseline, up to 3 years
Secondary outcome [5] 0 0
Randomized Cohort: Change From Baseline of the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) Score
Timepoint [5] 0 0
Baseline, up to 3 years
Secondary outcome [6] 0 0
Randomized Cohort: the Change From Baseline of the Functional Assessment of Cancer Therapy (FACT) Colorectal Symptom Index (FCSI) Score
Timepoint [6] 0 0
Baseline, up to 3 years
Secondary outcome [7] 0 0
Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time
Timepoint [7] 0 0
Up to end of treatment (approximately 3 years)
Secondary outcome [8] 0 0
Safety Run-in and Randomized Cohorts: Antidrug Antibodies (ADA) to Magrolimab
Timepoint [8] 0 0
Up to end of treatment (approximately 3 years)

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2026
Actual
Sample size
Target
135
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Westmead Hospital - Blacktown
Recruitment hospital [2] 0 0
Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [3] 0 0
Southside Cancer Care Centre - Miranda
Recruitment hospital [4] 0 0
Genesis Care North Shore - St Leonards
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [7] 0 0
Austin Health - Heidelberg
Recruitment hospital [8] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2228 - Miranda
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5042 - Bedford Park
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Belgium
State/province [13] 0 0
Haine-Saint-Paul
Country [14] 0 0
Belgium
State/province [14] 0 0
Libramont-Chevigny
Country [15] 0 0
Canada
State/province [15] 0 0
Ottawa
Country [16] 0 0
Canada
State/province [16] 0 0
Toronto
Country [17] 0 0
France
State/province [17] 0 0
Besançon
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Tours
Country [21] 0 0
Germany
State/province [21] 0 0
Dresden
Country [22] 0 0
Germany
State/province [22] 0 0
Munchen
Country [23] 0 0
Hong Kong
State/province [23] 0 0
Hong Kong
Country [24] 0 0
Italy
State/province [24] 0 0
Meldola
Country [25] 0 0
Italy
State/province [25] 0 0
Padova
Country [26] 0 0
Italy
State/province [26] 0 0
Pisa
Country [27] 0 0
Italy
State/province [27] 0 0
San Giovanni Rotondo
Country [28] 0 0
Italy
State/province [28] 0 0
Vicenza
Country [29] 0 0
Puerto Rico
State/province [29] 0 0
San Juan
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
L'Hospitalet de Llobregat
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05330429
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05330429