Clinical trial NCT05330429: Study of Magrolimab Given Together With FOLFIRI/BEV in Patients With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2022-04-15
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: First dose date up to 28 days
measure: Safety Run-in Cohort: Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0
timeFrame: First dose date up to 3 years
measure: Safety Run-in Cohort: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0
timeFrame: First dose date up to 3 years
measure: Randomized Cohort: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to 3 years
Secondary outcomes:
measure: Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment Using RECIST Version 1.1
timeFrame: Up to 3 years
measure: Randomized Cohort: Duration of Response (DOR) as Assessed by Investigator Assessment Per RECIST Version 1.1
timeFrame: Up to 3 years
measure: Randomized Cohort: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Randomized Cohort: Change From Baseline of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire EORTC-QLQ-C30 Score
timeFrame: Baseline, up to 3 years
measure: Randomized Cohort: Change From Baseline of the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) Score
timeFrame: Baseline, up to 3 years
measure: Randomized Cohort: the Change From Baseline of the Functional Assessment of Cancer Therapy (FACT) Colorectal Symptom Index (FCSI) Score
timeFrame: Baseline, up to 3 years
measure: Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time
timeFrame: Up to end of treatment (approximately 3 years)
measure: Safety Run-in and Randomized Cohorts: Antidrug Antibodies (ADA) to Magrolimab
timeFrame: Up to end of treatment (approximately 3 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope ( City of Hope National Medical Center, City of Hope Medical Center )
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Redondo Beach
country: United States
facility: Torrance Memorial Physician Network
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
city: Westwood
country: United States
facility: University of Kansas
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York, PC
state: New York
city: Rochester
country: United States
facility: AdventHealth
state: New York
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Medical Center
state: Texas
city: Arlington
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance (SCCA)
state: Washington
city: Blacktown
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre
state: New South Wales
city: Miranda
country: Australia
facility: Southside Cancer Care Centre
state: New South Wales
city: St Leonards
country: Australia
facility: Genesis Care North Shore
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Haine-Saint-Paul
country: Belgium
facility: Hôpital de Jolimont
city: Libramont-Chevigny
country: Belgium
facility: Centre Hospitalizer De L'Ardenne
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: BesanÃ§on
country: France
facility: Centre Hospitalier Regional Universitaire Hopital Besancon
city: Lyon
country: France
facility: Centre Léon Bérard - Centre de Lutte contre le Cancer
city: Paris
country: France
facility: Hopital franco brittanique
city: Tours
country: France
facility: CHU de Tours
city: Dresden
country: Germany
facility: Carl Gustav Carus Management GMBH
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der TU Munchen Zentrum fur klinische Studien der Klinik und Poliklinik fur Innere Medizin III
city: Hong Kong
country: Hong Kong
facility: Hong Kong Integrated Oncology Centre
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - Medical Oncology Department
city: Padova
country: Italy
facility: Istituto Oncologico Veneto (IOV)- IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana- UO Oncologia Medica
city: San Giovanni Rotondo
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Clinico Humanitas
city: Vicenza
country: Italy
facility: San Bortolo General Hospital- Oncology Department
city: San Juan
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia- Hospital Duran I Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital HM Sanchinarro
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: