Study of Magrolimab in Patients With Solid Tumors
- Registration Number
- NCT04827576
- Lead Sponsor
- Gilead Sciences
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 106
- 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
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Positive serum pregnancy test.
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Breastfeeding female.
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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.
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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.
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History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
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Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
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Prior treatment with cluster of differentiation (CD)47 or signal regulatory protein alpha-targeting agents.
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Current participation in another interventional clinical study.
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Known inherited or acquired bleeding disorders.
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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.
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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.
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Known active or chronic hepatitis B or C infection or human immunodeficiency virus.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2 Cohort 1c, mSCLC (Magrolimab + Docetaxel) Docetaxel Participants with mSCLC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 72 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 72 weeks; each cycle length = 21 days. Safety Run-in Cohort 1 (Magrolimab + Docetaxel) Magrolimab Participants with solid tumors (including metastatic non small cell lung cancer (mNSCLC), metastatic urothelial cancer (mUC), and metastatic small cell lung cancer (mSCLC)) will receive 1 mg/kg magrolimab intravenously (IV) on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 113 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 113 weeks; each cycle length = 21 days. Safety Run-in Cohort 1 (Magrolimab + Docetaxel) Docetaxel Participants with solid tumors (including metastatic non small cell lung cancer (mNSCLC), metastatic urothelial cancer (mUC), and metastatic small cell lung cancer (mSCLC)) will receive 1 mg/kg magrolimab intravenously (IV) on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 113 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 113 weeks; each cycle length = 21 days. Phase 2 Cohort 1a, mNSCLC (Magrolimab + Docetaxel) Magrolimab Participants with mNSCLC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 90 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 69 weeks; each cycle length = 21 days. Phase 2 Cohort 1a, mNSCLC (Magrolimab + Docetaxel) Docetaxel Participants with mNSCLC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 90 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 69 weeks; each cycle length = 21 days. Phase 2 Cohort 1b, mUC (Magrolimab + Docetaxel) Magrolimab Participants with mUC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 68 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 68 weeks; each cycle length = 21 days. Phase 2 Cohort 1b, mUC (Magrolimab + Docetaxel) Docetaxel Participants with mUC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 68 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 68 weeks; each cycle length = 21 days. Phase 2 Cohort 1c, mSCLC (Magrolimab + Docetaxel) Magrolimab Participants with mSCLC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 72 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 72 weeks; each cycle length = 21 days.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) First dose date up to 113 weeks plus 30 days TEAEs were defined as any adverse events (AE) not present prior to the study treatment, or any events already present but worsening in either intensity or frequency following exposure to the study treatment. The TEAE reporting period is defined as the period from the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment or the day before initiation of subsequent antineoplastic therapy, whichever comes first. An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution.
Percentage of Participants With Treatment-Emergent Laboratory Abnormalities First dose date up to 113 weeks plus 30 days Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days and prior to the day of initiation of subsequent anti-cancer therapy. Percentages were rounded off.
Objective Response Rate (ORR) (Phase 2 Cohorts 1a, 1b, and 1c) Up to 90 Weeks ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR), as measured by RECIST version 1.1, as determined by investigator assessment. 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 method was used in outcome measure analysis. Percentages were rounded-off.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) (Phase 2 Cohorts 1a, 1b, and 1c) Up to 117 Weeks PFS was defined as the interval from the first dosing date of any study drug to the earlier date of the first documentation of objective disease progression (PD) by investigator assessment per RECIST, Version 1.1, or death from any cause. PD is 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. (the appearance of one or more new lesions was also considered progression). Kaplan-Meier (KM) estimates were used in outcome measure analysis.
Duration of Response (DOR) (Phase 2 Cohorts 1a, 1b, and 1c) Up to 117 Weeks DOR was defined as time from first documentation of CR or PR to the earliest date of documented PD, per RECIST, Version 1.1, or death from any cause, whichever occurs first, as determined by investigator assessment. CR and PR are defined in outcome measure #3 and PD is defined in outcome measure #4. KM Estimates were used in outcome measure analysis.
Overall Survival (OS) (Phase 2 Cohorts 1a, 1b, and 1c) Up to 117 Weeks OS is defined as time from date of dose initiation to death from any cause. KM estimates were used in outcome measure analysis.
Serum Concentration of Magrolimab 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 Percentage of Participants Who Developed Anti-Magrolimab Antibodies Up to 113 Weeks
Trial Locations
- Locations (48)
Tallahassee Memorial Healthcare Cancer Center
🇺🇸Tallahassee, Florida, United States
University of Miami
🇺🇸Deerfield Beach, Florida, United States
Virginia Piper Cancer Center (Alliant Health)
🇺🇸Saint Paul, Minnesota, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Comprehensive Cancer Centers of Nevada- Twain Office
🇺🇸Las Vegas, Nevada, United States
Cancer Treatment Centers of America
🇺🇸Goodyear, Arizona, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
Southeastern regional Medical Center
🇺🇸Newnan, Georgia, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Providence Saint John's Health Center
🇺🇸Santa Monica, California, United States
St. Jude Hospital Yorba dba St. Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
University Center and Blood Center,LLC.
🇺🇸Athens, Georgia, United States
Orchard Healthcare Research Inc
🇺🇸Skokie, Illinois, United States
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-benite, France
Hospital del Mar
🇪🇸Barcelona, Spain
Centre de Lutte Contre le Cancer (CLCC) - Centre Antoine Lacassagne (CAL) - Site Est
🇫🇷Nice, France
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Medical Oncology Associates,PS (dba Summit Cancer Center) (includes IP Shipment)
🇺🇸Spokane, Washington, United States
Instituto de Investigacion Oncologica Vall de Hebron
🇪🇸Barcelona, Spain
Centre Hospitalier Regional Universitaire de Lille
🇫🇷Lille, France
Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
Hospital De La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario de Jaen
🇪🇸Jaen, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Centre Georges François Leclerc
🇫🇷Dijon, France
Charleston Oncology
🇺🇸Charleston, South Carolina, United States
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Hôpital de la Pitié Salpétrière
🇫🇷Paris, France
Saint Alphonsus Cancer Institute Caldwell
🇺🇸Caldwell, Idaho, United States
Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hopital Nord AP-HM
🇫🇷Marseille, France
Instytut Centrum Zdrowia Matki Polki
🇵🇱Lodz, Poland
Wojewodzki Szpital Specjalistyczny w Siedlcach
🇵🇱Siedlce, Poland
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Institut Bergonie
🇫🇷Bordeaux, France
Institut de Cancérologie de l'Ouest (ICO) - Saint-Herblain
🇫🇷Saint Herblain, France
Centre LÃon BÃrard Centre RÃgional de Lutte Contre Le Cancer
🇫🇷Lyon, France
Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Barts Health NHS Trust
🇬🇧London, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom