Clinical trial NCT04958785: Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer
Official title: A Phase 2 Study of Magrolimab Combination Therapy in Patients With Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Triple-Negative Breast Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-07-12
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: 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 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.

Eligibility criteria: Key Inclusion criteria:

* Adequate performance status, hematologic, renal and liver function.
* Measurable disease per RECIST v1.1
* Cohort 1: Individuals with previously untreated with systemic therapy for unresectable locally advanced or metastatic TNBC that are considered PD-L1 negative (as determined by an approved test according to local regulations).
* Cohort 2: Individuals with unresectable, locally advanced or metastatic breast cancer with a diagnosis of TNBC who have received at least 1 and no more than 2 prior lines of systemic therapy in the unresectable, locally advanced or metastatic setting. Individuals must have been previously treated with a taxane in any setting. Individuals with tumors that are considered positive for PD-L1 expression (as determined by an approved test according to local regulations) must have received an immune checkpoint inhibitor for a prior-line of treatment for unresectable locally advanced/metastatic TNBC.

Key Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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
timeFrame: First dose date up to 35 months
measure: Phase 2 Cohort 1: PFS as Determined by Investigator Assessment Using RECIST Version 1.1
timeFrame: Up to 35 months
measure: 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
timeFrame: Up to 35 months
Secondary outcomes:
measure: Phase 2 Cohort 1: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment
timeFrame: Up to 35 months
measure: Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): PFS as Determined by Investigator Assessment Using RECIST Version 1.1
timeFrame: Up to 35 months
measure: 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
timeFrame: Up to 35 months
measure: Phase 2 Cohort 1 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Overall Survival (OS)
timeFrame: Up to 35 months
measure: 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
timeFrame: First dose date up to 35 months
measure: Magrolimab Concentration Versus Time
timeFrame: Up to end of treatment (approximately 35 months)
measure: Antidrug Antibodies (ADA) to Magrolimab
timeFrame: Up to end of treatment (approximately 35 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Fresno
country: United States
facility: Women's Cancer Care
state: California
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Monica
country: United States
facility: Saint John's Cancer Institute
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center,LLC
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute Emory University
state: Georgia
city: Newnan
country: United States
facility: Southeastern Regional Medical Center, LLC
state: Georgia
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: New York
country: United States
facility: NYU Investigational Pharmacy, Laura & Isaac Perlmutter Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Charleston
country: United States
facility: Charleston Oncology
state: South Carolina
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Cairns
country: Australia
facility: Cairns and Hinterland Hospital and Health Service
state: Queensland
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research SA
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Health
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health- University Hospital Geelong
state: Victoria
city: Wendouree
country: Australia
facility: Ballarat Oncology & Haematology Services
state: Victoria
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Kowloon
country: Hong Kong
facility: Princess Margaret Hospital
city: New Territories
country: Hong Kong
facility: Prince of Wales Hospital
city: Gangnam-Gu
country: Korea, Republic of
facility: Samsung Medical Center
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Jongrogu
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Beitou District
country: Taiwan
facility: Taipei Veterans General Hospital
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
city: Guishan District
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Sanmin District
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Tapiei
country: Taiwan
facility: National Taiwan University Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: London
country: United Kingdom
facility: University College London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: