Study to Evaluate the Safety and Efficacy of Magrolimab Combination Therapy in Adults With Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer

Sponsor

Gilead Sciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04958785

Collaborator

(none)

144

Enrollment

Locations

Arms

36.6

Anticipated Duration (Months)

7.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Triple-Negative Breast Cancer	Biological: Magrolimab Drug: Nab-Paclitaxel Drug: Paclitaxel Drug: Sacituzumab govitecan	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 14, 2021

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or 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.	Biological: Magrolimab Administered intravenously Other Names: GS-4721 Drug: Nab-Paclitaxel Administered intravenously Other Names: Abraxane Drug: Paclitaxel Administered intravenously Other Names: Taxol®
Experimental: Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or 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.	Biological: Magrolimab Administered intravenously Other Names: GS-4721 Drug: Nab-Paclitaxel Administered intravenously Other Names: Abraxane Drug: Paclitaxel Administered intravenously Other Names: Taxol®
Active Comparator: Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or 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.	Biological: Magrolimab Administered intravenously Other Names: GS-4721 Drug: Nab-Paclitaxel Administered intravenously Other Names: Abraxane Drug: Paclitaxel Administered intravenously Other Names: Taxol®
Experimental: Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan Participants with unresectable, locally advanced or metastatic TNBC who have received 1 prior line 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.	Biological: Magrolimab Administered intravenously Other Names: GS-4721 Drug: Sacituzumab govitecan Administered intravenously Other Names: GS-0132 Trodelvy®
Experimental: Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan 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.	Biological: Magrolimab Administered intravenously Other Names: GS-4721 Drug: Sacituzumab govitecan Administered intravenously Other Names: GS-0132 Trodelvy®

Outcome Measures

Primary Outcome Measures

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]
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.
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.

Secondary Outcome Measures

Phase 2 Cohort 1: 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): Objective Response Rate (ORR) as Determined by Independent Central Review [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 independent central review.
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): PFS as Determined by Independent Central Review 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 independent central review 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 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Duration of Response (DOR) as Determined by Independent Central Review 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 independent central review 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): Overall Survival (OS) [Up to 35 months]
OS is defined as time from date of randomization to death from any cause.
Magrolimab Concentration Versus Time [Up to end of treatment (approximately 35 months)]
Antidrug Antibodies (ADA) to Magrolimab [Up to end of treatment (approximately 35 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion criteria:

Adequate performance status, hematologic, renal and liver function
Measurable disease per RECIST v1.1
Cohort 1: Individuals with previously untreated 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 TNBC who have received 1 prior line of therapy in the advanced setting (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 first-line treatment of 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 (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids 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 or rapid visceral progression and/or symptomatic disease, where single-agent chemotherapy would not be appropriate.
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 neuropathy or alopecia 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Women's Cancer Care	Fresno	California	United States	93710
2	Providence Medical Foundation	Fullerton	California	United States	92835
3	Saint John's Cancer Institute	Santa Monica	California	United States	90404
4	Providence Medical Foundation	Santa Rosa	California	United States	95403
5	Tallahassee Memorial Healthcare Cancer Center	Tallahassee	Florida	United States	32308
6	University Cancer & Blood Center,LLC	Athens	Georgia	United States	30607
7	Orchard Healthcare Research Inc	Skokie	Illinois	United States	60077
8	Allina Health Cancer Institute	Minneapolis	Minnesota	United States	55407
9	Astera Cancer Care	East Brunswick	New Jersey	United States	08816
10	NYU Investigational Pharmacy, Laura & Isaac Perlmutter Cancer Center	New York	New York	United States	10016
11	Stony Brook University	Stony Brook	New York	United States	11794
12	Charleston Oncology	Charleston	South Carolina	United States	29414
13	Cairns and Hinterland Hospital and Health Service	Cairns	Queensland	Australia	4870
14	University of the Sunshine Coast	Sippy Downs	Queensland	Australia	4556
15	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
16	Cancer Research SA	Adelaide	South Australia	Australia	5000
17	Box Hill Hospital	Box Hill	Victoria	Australia	3128
18	Hong Kong United Oncology Centre	Hong Kong		Hong Kong
19	Queen Mary Hospital	Hong Kong		Hong Kong