Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer

Triple-Negative Breast Cancer Clinical Trial

— ELEVATE TNBC  

Official title:

A Phase 2 Study of Magrolimab Combination Therapy in Patients With Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04958785
• Other study ID #: GS-US-586-6144
• Secondary ID: 2021-001074-27
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 14, 2021
• Est. completion date: January 2025

Study information

• Verified date: March 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 92
• Est. completion date: January 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Cancer

Intervention

Drug:
• Magrolimab
Administered intravenously
• Nab-Paclitaxel
Administered intravenously
• Paclitaxel
Administered intravenously
• Sacituzumab Govitecan-hziy
Administered intravenously

Locations

Country	Name	City	State
Australia	Cancer Research SA	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Cairns and Hinterland Hospital and Health Service	Cairns	Queensland
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Peninsula Health	Frankston	Victoria
Australia	Barwon Health- University Hospital Geelong	Geelong	Victoria
Australia	University of the Sunshine Coast	Sippy Downs	Queensland
Australia	Ballarat Oncology & Haematology Services	Wendouree	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Princess Margaret Hospital	Kowloon
Hong Kong	Prince of Wales Hospital	New Territories
Korea, Republic of	Samsung Medical Center	Gangnam-Gu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Hospital	Jongrogu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Taiwan	Taipei Veterans General Hospital	Beitou District
Taiwan	Changhua Christian Hospital	Changhua City
Taiwan	Chang Gung Memorial Hospital, Linkou	Guishan District
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Sanmin District
Taiwan	National Taiwan University Hospital	Tapiei
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester
United Kingdom	University College London	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University Cancer & Blood Center,LLC	Athens	Georgia
United States	Winship Cancer Institute Emory University	Atlanta	Georgia
United States	Charleston Oncology	Charleston	South Carolina
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Women's Cancer Care	Fresno	California
United States	Providence Medical Foundation	Fullerton	California
United States	Mayo Clinic	Jacksonville	Florida
United States	Allina Health Cancer Institute	Minneapolis	Minnesota
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	NYU Investigational Pharmacy, Laura & Isaac Perlmutter Cancer Center	New York	New York
United States	Southeastern Regional Medical Center, LLC	Newnan	Georgia
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Saint John's Cancer Institute	Santa Monica	California
United States	Providence Medical Foundation	Santa Rosa	California
United States	Orchard Healthcare Research Inc	Skokie	Illinois
United States	Stony Brook University	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Hong Kong,  Korea, Republic of,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 2 Cohort 1: PFS as Determined by Investigator Assessment Using RECIST Version 1.1	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.	Up to 35 months
Primary	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	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.	Up to 35 months
Secondary	Phase 2 Cohort 1: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment	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.	Up to 35 months
Secondary	Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): PFS as Determined by Investigator Assessment Using RECIST Version 1.1	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.	Up to 35 months
Secondary	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	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.	Up to 35 months
Secondary	Phase 2 Cohort 1 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Overall Survival (OS)	OS is defined as time from date of randomization to death from any cause.	Up to 35 months
Secondary	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
Secondary	Magrolimab Concentration Versus Time		Up to end of treatment (approximately 35 months)
Secondary	Antidrug Antibodies (ADA) to Magrolimab		Up to end of treatment (approximately 35 months)

External Links

•   Gilead Clinical Trials Website