Clinical trial NCT04827576: Study of Magrolimab in Patients With Solid Tumors
Official title: A Phase 2, Multi-Arm Study of Magrolimab in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Solid Tumor
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of magrolimab in combination with docetaxel in participants with solid tumors.

Detailed description: This study will consist of a Safety Run-in Cohort 1 (magrolimab + docetaxel combination). After completion of the Safety Run-in Cohort 1, Phase 2 Cohort 1 will occur as follows:

* Phase 2 Cohort 1: a cohort of participants with solid tumors (metastatic non-small cell lung cancer (mNSCLC) (Phase 2 Cohort 1a), metastatic urothelial cancer (mUC) (Phase 2 Cohort 1b), and metastatic small cell lung cancer (mSCLC) (Phase 2 Cohort 1c).

Eligibility criteria: Key Inclusion Criteria:

* Individual must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
* Adequate blood counts.
* Adequate renal function.
* Adequate liver function.
* Pretreatment blood cross-match completed.
* Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
* Measurable disease according to response evaluation criteria in solid tumours (RECIST) version 1.1

Cohort-Specific Inclusion Criteria:

* Safety Run-in Cohort 1: Individuals with metastatic advanced solid tumors who have had at least 1 prior line of systemic anticancer therapy (metastatic non-small cell lung cancer (mNSCLC) and metastatic small cell lung cancer (mSCLC)) in a locally advanced/metastatic setting, or 2 prior lines of systemic anticancer therapy (metastatic urothelial cancer (mUC)) in a locally advanced/metastatic setting, and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting.
* Phase 2 Cohort 1a (mNSCLC): Individuals with NSCLC who have had treatment with platinum-based chemotherapy and immune checkpoint inhibitor therapy in a locally advanced/metastatic setting, either in combination or sequentially (unless not eligible for one of these therapies) are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded. Individuals whose tumors have genomic alterations are excluded.
* Phase 2 Cohort 1b (mUC): Individuals with UC who have had prior treatment with systemic chemotherapy and immune checkpoint inhibitor therapy in a locally advanced/metastatic setting (unless not eligible for one of these therapies) are eligible. At least 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are required and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded.
* Phase 2 Cohort 1c (mSCLC): Individuals with SCLC who have had prior treatment with platinum-based chemotherapy and/or immune checkpoint inhibitor therapy are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded.

Note: Maintenance therapies are not counted as separate lines of therapy.

Key Exclusion Criteria:

* Positive serum pregnancy test.
* Breastfeeding female.
* 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 red blood cell transfusions during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criteria.
* 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.
* Prior treatment with cluster of differentiation (CD)47 or signal regulatory protein alpha-targeting agents.
* Current participation in another interventional clinical study.
* 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. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.
* Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and who are in complete remission for over 3 years.
* Known active or chronic hepatitis B or C infection or human immunodeficiency virus.
* Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted.

  * Note: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone releasing hormone agonists for prostate or breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa B ligand (RANKL) inhibitors are not criteria for exclusion.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to 113 weeks plus 30 days
measure: Percentage of Participants With Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to 113 weeks plus 30 days
measure: Objective Response Rate (ORR) (Phase 2 Cohorts 1a, 1b, and 1c)
timeFrame: Up to 90 Weeks
Secondary outcomes:
measure: Progression-free Survival (PFS) (Phase 2 Cohorts 1a, 1b, and 1c)
timeFrame: Up to 117 Weeks
measure: Duration of Response (DOR) (Phase 2 Cohorts 1a, 1b, and 1c)
timeFrame: Up to 117 Weeks
measure: Overall Survival (OS) (Phase 2 Cohorts 1a, 1b, and 1c)
timeFrame: Up to 117 Weeks
measure: Serum Concentration of Magrolimab
timeFrame: Day 1, Day 8 Predose, Day 8 1-Hour Postdose, Day 22, Day 43 Predose, Day 43 1-Hour Postdose, Day 85, Day 127, Day 190 and Day 253 Predose
measure: Percentage of Participants Who Developed Anti-Magrolimab Antibodies
timeFrame: Up to 113 Weeks
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Cancer Treatment Centers of America
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center
state: California
city: Santa Rosa
country: United States
facility: St. Jude Hospital Yorba dba St. Joseph Heritage Healthcare
state: California
city: Deerfield Beach
country: United States
facility: University of Miami
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Healthcare Cancer Center
state: Florida
city: Athens
country: United States
facility: University Center and Blood Center,LLC.
state: Georgia
city: Newnan
country: United States
facility: Southeastern regional Medical Center
state: Georgia
city: Caldwell
country: United States
facility: Saint Alphonsus Cancer Institute Caldwell
state: Idaho
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Paul
country: United States
facility: Virginia Piper Cancer Center (Alliant Health)
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada- Twain Office
state: Nevada
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Charleston
country: United States
facility: Charleston Oncology
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Spokane
country: United States
facility: Medical Oncology Associates,PS (dba Summit Cancer Center) (includes IP Shipment)
state: Washington
city: Bordeaux
country: France
facility: Institut Bergonie
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille
city: Lyon
country: France
facility: Centre LÃon BÃrard Centre RÃgional de Lutte Contre Le Cancer
city: Marseille
country: France
facility: Hopital Nord AP-HM
city: Nice
country: France
facility: Centre de Lutte Contre le Cancer (CLCC) - Centre Antoine Lacassagne (CAL) - Site Est
city: Paris
country: France
facility: Hôpital de la Pitié Salpétrière
city: Pierre-benite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest (ICO) - Saint-Herblain
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Siedlce
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Siedlcach
city: Barcelona
country: Spain
facility: Instituto de Investigacion Oncologica Vall de Hebron
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital De La Santa Creu I Sant Pau
city: Jaen
country: Spain
facility: Hospital Universitario de Jaen
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital HM Sanchinarro
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Van Burren N, U'Ren L, Song K, Liu Y, Correa P, Tang S, et al. Biomarker analysis of magrolimab plus docetaxel in patients with 2L+ mNSCLC from ELEVATE Lung and UC, a Phase 2 multicohort study [Abstract]. J Immunother Cancer. 2024;12. doi:10.1136/jitc- 2024-SITC2024.0184.
citation: Van Burren N, U'Ren L, Song K, Liu Y, Correa P, Tang S, et al. Biomarker analysis of magrolimab plus docetaxel in patients with 2L+ mNSCLC from ELEVATE Lung and UC, a Phase 2 multicohort study. Poster presented at: 2024 Society for Immunotherapy of Cancer (SITC); 2024 Nov 6-10; Houston, TX, USA.
citation: Juan-Vidal O, Fang B, Paz-Ares LG, Ortega Granado AL, Vicuna BD, Bodnar L, et al. Magrolimab + docetaxel in previously treated patients with metastatic non-small cell lung cancer [Abstract]. J Immunother Cancer. 2024;12. doi:10.1136/jitc-2024-SITC2024.0604.
citation: Juan-Vidal O, Fang B, Paz-Ares LG, Ortega Granado AL, Vicuna BD, Bodnar L, et al. Magrolimab + docetaxel in previously treated patients with metastatic non-small cell lung cancer. Poster presented at: 2024 Society for Immunotherapy of Cancer (SITC); 2024 Nov 6-10; Houston, TX, USA.
citation: Vaishampayan UN, Puri S, Kummar S, Perez JM, Italiano A, Shao J, et al. A Phase 2 multiarm study of magrolimab in combination with docetaxel in patients with locally advanced or metastatic solid tumors: ELEVATE-Lung and UC. J Clin Oncol. 2023;41(16_suppl):TPS9142-TPS9142.
citation: Subbiah V, Vaishampayan UN, Puri S, Lin L, Chao M, Ramsingh G, et al. A Phase 2, multiarm study of anti-CD47 antibody, magrolimab, in combination with docetaxel in patients with locally advanced or metastatic solid tumors. J Clin Oncol. 2022;40(6_suppl):TPS584-TPS584.