A Phase 2 Study of Magrolimab Combination Therapy in Patients With Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 92
- 试验地点
- 42
- 主要终点
- Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of magrolimab in combination with nab-paclitaxel or paclitaxel (cohort 1) or with sacituzumab govitecan-hziy (cohort 2) in participants with non-surgically removable locally advanced or metastatic triple-negative breast cancer.
The primary objective of this study for the safety run-in cohorts of the study is to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with nab-paclitaxel or paclitaxel (Safety Run-In Cohort 1), and sacituzumab govitecan (Safety Run-In Cohort 2) in metastatic triple-negative breast cancer (mTNBC).
This study in the Phase 2 Cohort 1 also compares the efficacy of magrolimab in combination with nab-paclitaxel or paclitaxel versus nab-paclitaxel or paclitaxel alone, as determined by progression-free survival (PFS) by investigator assessment.
This study in the Phase 2 Cohort 2 also evaluates the efficacy of magrolimab in combination with sacituzumab govitecan as determined by confirmed objective response rate (ORR) by investigator assessment.
详细描述
The primary objective of this study for the safety run-in cohorts of the study is to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with nab-paclitaxel or paclitaxel (Safety Run-In Cohort 1), and sacituzumab govitecan (Safety Run-In Cohort 2) in metastatic triple-negative breast cancer (mTNBC).
The primary objective of this study for Phase 2 Cohort 1 is to compare the efficacy of magrolimab in combination with nab-paclitaxel or paclitaxel versus nab-paclitaxel or paclitaxel alone, as determined by progression-free survival (PFS) by investigator assessment.
The primary objective of this study for Phase 2 Cohort 2 is to evaluate the efficacy of magrolimab in combination with sacituzumab govitecan as determined by confirmed objective response rate (ORR) by investigator assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Positive serum pregnancy test or breastfeeding female.
- •Active central nervous system (CNS) disease. Individuals with asymptomatic and stable, treated CNS lesions (who have been off steroids, radiation and/or surgery and/or other CNS-directed therapy 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. Red blood cell 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.
- •Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha-targeting agents.
- •Known inherited or acquired bleeding disorders.
- •Cohort 1 only: Disease progression within 6 months following neoadjuvant/adjuvant therapy.
- •Cohort 2 only:
- •Individuals with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and Individuals with a history of bowel obstruction or gastrointestinal perforation within 6 months of enrollment.
- •Individuals who previously received topoisomerase I inhibitors or antibody-drug conjugates containing a topoisomerase inhibitor.
- •High-dose systemic corticosteroids (≥ 20 mg of prednisone or its equivalent) are not allowed within 2 weeks of Cycle 1 Day
- •Have not recovered (ie, ≥ Grade 2 is considered not recovered) from adverse events (AEs) due to a previously administered agent.
- •Note: Individuals with any grade of neuropathy, alopecia, hypo- or hyperthyroidism, or other endocrinopathies that are well controlled with hormone replacement are an exception to this criterion and will qualify for the study.
- •Note: if individuals received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel
Participants will receive magrolimab intravenous (IV) infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle;
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-days cycle.
干预措施: Magrolimab (Drug)
Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel
Participants will receive magrolimab intravenous (IV) infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle;
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-days cycle.
干预措施: Nab-Paclitaxel (Drug)
Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel
Participants will receive magrolimab intravenous (IV) infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle;
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-days cycle.
干预措施: Paclitaxel (Drug)
Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel
Participants will receive magrolimab IV infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle;
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-days cycle.
干预措施: Magrolimab (Drug)
Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel
Participants will receive magrolimab IV infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle;
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-days cycle.
干预措施: Nab-Paclitaxel (Drug)
Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel
Participants will receive magrolimab IV infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle;
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-days cycle.
干预措施: Paclitaxel (Drug)
Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel
Participants will receive nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-day cycle.
干预措施: Magrolimab (Drug)
Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel
Participants will receive nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-day cycle.
干预措施: Nab-Paclitaxel (Drug)
Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel
Participants will receive nab-paclitaxel IV or paclitaxel IV as mentioned below:
- Nab-paclitaxel 100 mg/m^2 or paclitaxel 90 mg/m^2 on Days 1, 8 and 15 of every 28-day cycle.
干预措施: Paclitaxel (Drug)
Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan
Participants will receive magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle;
- Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle.
干预措施: Magrolimab (Drug)
Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan
Participants will receive magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle;
- Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan
Participants will receive magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle;
- Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle.
干预措施: Magrolimab (Drug)
Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan
Participants will receive magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below:
- Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle;
- Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle.
干预措施: Sacituzumab Govitecan-hziy (Drug)
结局指标
主要结局
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)
时间窗: First dose date up to 28 days (Cohort 1) and up to 21 days (Cohort 2)
A DLT is defined as any: * Grade 3 or higher hematologic toxicity including: * Hemolytic anemia that is medically significant, requiring hospitalization or prolongation of existing hospitalization, disabling, or limiting self-care activities of daily life. * Event meeting Hy's Law criteria: * Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation (at least 3 x ULN), AND * Treatment-emergent total bilirubin elevation (more than 2 x ULN), and absence of cholestasis (defined as alkaline phosphatase less than 2 x ULN), AND * No other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, alcohol ingestion, congestive heart failure, worsening liver metastases). * Grade 3 or higher nonhematologic toxicity that has worsened in severity from pretreatment baseline during the DLT assessment period, and in the opinion of the investigator, the AE is at least possibly related to magrolimab.
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: First dose date up to last dose date (up to 73 weeks) plus 30 days
TEAEs are defined as any events 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. TEAEs were any AEs with an onset date on or after 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 anticancer therapy, whichever comes first. An AE is any untoward medical occurrence in a clinical study patient administered a study drug that does not necessarily have a causal relationship with the treatment.
Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0
时间窗: First dose date up to last dose date (up to 73 weeks) plus 30 days
Treatment-emergent laboratory abnormalities according to NCI CTCAE V5.0 are 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 before initiation of subsequent anti-cancer therapy. Grade 1 mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening and Grade 5 death. Percentages were rounded off.
Phase 2 Cohort 1: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Up to 107 weeks
PFS was defined as the time from the date of randomization until the earliest date of documented disease progression (PD), as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurred first. PD was 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. Kaplan-Meier (KM) estimates were used in outcome measure analysis.
Safety Run-in Cohort 2 and Phase 2 Cohort 2: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Up to 107 weeks
ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as determined at least 4 weeks after initial documentation of response by investigator assessment per RECIST v1.1. 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 estimates were used in outcome measure analysis. Percentages were rounded off.
次要结局
- Percentage of Participants With Antidrug Antibodies (ADA) to Magrolimab(Up to 73 weeks)
- Phase 2 Cohort 1: Confirmed ORR as Determined by Investigator Assessment Per RECIST, Version 1.1(Up to 107 weeks)
- Safety Run-in Cohort 2 and Phase 2 Cohort 2: PFS as Determined by Investigator Assessment Using RECIST Version 1.1(Up to 107 weeks)
- Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1(Up to 107 weeks)
- Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS)(Up to 107 weeks)
- Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs(First dose date up to last dose date (up to 73 weeks) plus 30 days)
- Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0(First dose date up to last dose date (up to 73 weeks) plus 30 days)
- Cohort 1 (Safety Run-in and Phase 2) and Cohort 2 (Safety Run-in and Phase 2): Concentration Levels of Magrolimab Over Time(Cohort 1: Predose - Day 1, 8, 22, 43, 85, 127, 190 and 253, Postdose 1 hour - Day 8 and 43; Cohort 2: Predose - Day 1, 8, 22, 43, 64, 85, 127, 190 and 253, Postdose 1 hour - Day 43 and 64)