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

Metastatic Colorectal Cancer Clinical Trial

— ELEVATE CRC  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05330429
• Other study ID #: GS-US-587-6156
• Secondary ID: 2022-500177-13
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 8, 2022
• Est. completion date: November 2026

Study information

• Verified date: April 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 135
• Est. completion date: November 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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 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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Magrolimab
Administered intravenously
• Bevacizumab
Administered intravenously
• Irinotecan
Administered intravenously
• Fluorouracil
Administered intravenously
• Leucovorin
Administered intravenously

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Hong Kong,  Italy,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		First dose date up to 28 days
Primary	Safety Run-in Cohort: Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0		First dose date up to 3 years
Primary	Safety Run-in Cohort: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0		First dose date up to 3 years
Primary	Randomized Cohort: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, or death from any cause, whichever occurs first.	Up to 3 years
Secondary	Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment Using RECIST Version 1.1	Confirmed ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) on 2 consecutive assessments, at least 28 days apart.	Up to 3 years
Secondary	Randomized Cohort: Duration of Response (DOR) as Assessed by Investigator Assessment Per RECIST Version 1.1	DOR is defined as time from first documentation of CR or PR to the earliest date of documented disease progression, or death from any cause, whichever occurs first.	Up to 3 years
Secondary	Randomized Cohort: Overall Survival (OS)	OS is defined as time from date of randomization to death from any cause.	Up to 3 years
Secondary	Randomized Cohort: Change From Baseline of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire EORTC-QLQ-C30 Score	The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is 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 indicate a higher level of symptoms (i.e. a worse state of the participant).	Baseline, up to 3 years
Secondary	Randomized Cohort: Change From Baseline of the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) Score	EQ-5D-5L is an instrument for use as a measure of health outcome.The EQ-5D-5L consists of 2 sections: the EuroQoL (5 dimensions) (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ-VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ-VAS indicate better health.	Baseline, up to 3 years
Secondary	Randomized Cohort: the Change From Baseline of the Functional Assessment of Cancer Therapy (FACT) Colorectal Symptom Index (FCSI) Score	The FCSI is a set of brief, clinically relevant, colorectal cancer symptoms for assessing symptomatic response. It comprises 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 are 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 are scored from "0" to "4" representing "Not at All" through to "Very Much True". The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state.	Baseline, up to 3 years
Secondary	Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time		Up to end of treatment (approximately 3 years)
Secondary	Safety Run-in and Randomized Cohorts: Antidrug Antibodies (ADA) to Magrolimab		Up to end of treatment (approximately 3 years)

External Links

•   Gilead Clinical Trials Website