Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer
- Conditions
- Triple-Negative Breast Cancer
- Interventions
- Registration Number
- NCT04958785
- 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 nab-paclitaxel or paclitaxel (cohort 1) or with sacituzumab govitecan-hziy (cohort 2) in patients with non-surgically removable locally advanced or metastatic triple-negative breast cancer.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 92
Not provided
-
Positive serum pregnancy test or breastfeeding female.
-
Active 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.
-
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 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 1.
-
Have not recovered (ie, ≥ Grade 2 is considered not recovered) from 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel Nab-Paclitaxel Participants with untreated unresectable, locally advanced or metastatic TNBC whose tumors are not appropriate for immune checkpoint inhibitor therapy will receive the following: * magrolimab in de-escalating doses to establish RP2D * nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel Nab-Paclitaxel Participants with mTNBC will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Magrolimab will be continued until development of unacceptable toxicity that cannot be clinically managed by dose or schedule modifications. Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity. Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel Nab-Paclitaxel Participants with mTNBC will receive nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity. Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel Paclitaxel Participants with untreated unresectable, locally advanced or metastatic TNBC whose tumors are not appropriate for immune checkpoint inhibitor therapy will receive the following: * magrolimab in de-escalating doses to establish RP2D * nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel Paclitaxel Participants with mTNBC will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Magrolimab will be continued until development of unacceptable toxicity that cannot be clinically managed by dose or schedule modifications. Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity. Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel Paclitaxel Participants with mTNBC will receive nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity. Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan Sacituzumab Govitecan-hziy Participants with unresectable, locally advanced or metastatic TNBC who have received at least 1 and no more than 2 prior lines of treatment in the unresectable, locally advanced or metastatic setting will receive the following: * magrolimab in de-escalating doses to establish RP2D * sacituzumab govitecan on Days 1 and 8 Each cycle is 21 days. Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan Magrolimab Participants with mTNBC will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with sacituzumab govitecan on Days 1 and 8. Each cycle is 21 days. Magrolimab will be continued until development of unacceptable toxicity that cannot be clinically managed by dose or schedule modifications.sacituzumab govitecan will be continued until development of unacceptable toxicity. Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan Sacituzumab Govitecan-hziy Participants with mTNBC will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with sacituzumab govitecan on Days 1 and 8. Each cycle is 21 days. Magrolimab will be continued until development of unacceptable toxicity that cannot be clinically managed by dose or schedule modifications.sacituzumab govitecan will be continued until development of unacceptable toxicity. Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel Magrolimab Participants with untreated unresectable, locally advanced or metastatic TNBC whose tumors are not appropriate for immune checkpoint inhibitor therapy will receive the following: * magrolimab in de-escalating doses to establish RP2D * nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel Magrolimab Participants with mTNBC will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Magrolimab will be continued until development of unacceptable toxicity that cannot be clinically managed by dose or schedule modifications. Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity. Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel Magrolimab Participants with mTNBC will receive nab-paclitaxel or paclitaxel administered according to local guidelines. Each cycle is 28 days. Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity. Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan Magrolimab Participants with unresectable, locally advanced or metastatic TNBC who have received at least 1 and no more than 2 prior lines of treatment in the unresectable, locally advanced or metastatic setting will receive the following: * magrolimab in de-escalating doses to establish RP2D * sacituzumab govitecan on Days 1 and 8 Each cycle is 21 days.
- Primary Outcome Measures
Name Time Method Safety Run-in Cohorts: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0 First dose date up to 35 months Cohort 2 (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 Up to 35 months The objective response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Phase 2 Cohort 1: PFS as Determined by Investigator Assessment Using RECIST Version 1.1 Up to 35 months PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Magrolimab Concentration Versus Time Up to end of treatment (approximately 35 months) Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): PFS as Determined by Investigator Assessment Using RECIST Version 1.1 Up to 35 months PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first.
Phase 2 Cohort 1 and Cohort 2 (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 35 months DOR is defined as time from first documentation of complete response or partial response to the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first.
Phase 2 Cohort 1: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment Up to 35 months ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), as measured by RECIST version 1.1, as determined by investigator assessment.
Phase 2 Cohort 1 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Overall Survival (OS) Up to 35 months OS is defined as time from date of randomization to death from any cause.
Antidrug Antibodies (ADA) to Magrolimab Up to end of treatment (approximately 35 months) Phase 2 Cohort 1 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Percentage of Participants Experiencing AEs and Laboratory Abnormalities According to NCI CTCAE, Version 5.0 First dose date up to 35 months
Trial Locations
- Locations (42)
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Charleston Oncology
🇺🇸Charleston, South Carolina, United States
Peninsula Health
🇦🇺Frankston, Victoria, Australia
Barwon Health- University Hospital Geelong
🇦🇺Geelong, Victoria, Australia
Chang Gung Memorial Hospital, Linkou
🇨🇳Guishan District, Taiwan
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Changhua Christian Hospital
🇨🇳Changhua City, Taiwan
Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Sanmin District, Taiwan
Providence Medical Foundation
🇺🇸Santa Rosa, California, United States
Women's Cancer Care
🇺🇸Fresno, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Saint John's Cancer Institute
🇺🇸Santa Monica, California, United States
University Cancer & Blood Center,LLC
🇺🇸Athens, Georgia, United States
Winship Cancer Institute Emory University
🇺🇸Atlanta, Georgia, United States
Orchard Healthcare Research Inc
🇺🇸Skokie, Illinois, United States
Southeastern Regional Medical Center, LLC
🇺🇸Newnan, Georgia, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Allina Health Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
NYU Investigational Pharmacy, Laura & Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Stony Brook University
🇺🇸Stony Brook, New York, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Cairns and Hinterland Hospital and Health Service
🇦🇺Cairns, Queensland, Australia
University of the Sunshine Coast
🇦🇺Sippy Downs, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Cancer Research SA
🇦🇺Adelaide, South Australia, Australia
Ballarat Oncology & Haematology Services
🇦🇺Wendouree, Victoria, Australia
Prince of Wales Hospital
🇭🇰New Territories, Hong Kong
Samsung Medical Center
🇰🇷Gangnam-Gu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Jongrogu, Korea, Republic of
Taipei Veterans General Hospital
🇨🇳Beitou District, Taiwan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
National Taiwan University Hospital
🇨🇳Tapiei, Taiwan
University College London
🇬🇧London, United Kingdom
University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Princess Margaret Hospital
🇭🇰Kowloon, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong