Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer (ELEVATE TNBC)
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| ClinicalTrials.gov Identifier: NCT04958785 |
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Recruitment Status :
Recruiting
First Posted : July 12, 2021
Last Update Posted : May 16, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Triple-Negative Breast Cancer | Drug: Magrolimab Drug: Nab-Paclitaxel Drug: Paclitaxel Drug: Sacituzumab Govitecan-hziy | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated 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 : | December 14, 2021 |
| Estimated Primary Completion Date : | August 2024 |
| Estimated Study Completion Date : | January 2025 |
| Arm | Intervention/treatment |
|---|---|
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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:
Each cycle is 28 days. |
Drug: Magrolimab
Administered intravenously
Other Name: GS-4721 Drug: Nab-Paclitaxel Administered intravenously
Other Name: Abraxane Drug: Paclitaxel Administered intravenously
Other Name: Taxol® |
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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. |
Drug: Magrolimab
Administered intravenously
Other Name: GS-4721 Drug: Nab-Paclitaxel Administered intravenously
Other Name: Abraxane Drug: Paclitaxel Administered intravenously
Other Name: Taxol® |
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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. |
Drug: Magrolimab
Administered intravenously
Other Name: GS-4721 Drug: Nab-Paclitaxel Administered intravenously
Other Name: Abraxane Drug: Paclitaxel Administered intravenously
Other Name: Taxol® |
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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:
Each cycle is 21 days. |
Drug: Magrolimab
Administered intravenously
Other Name: GS-4721 Drug: Sacituzumab Govitecan-hziy Administered intravenously
Other Names:
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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. |
Drug: Magrolimab
Administered intravenously
Other Name: GS-4721 Drug: Sacituzumab Govitecan-hziy Administered intravenously
Other Names:
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- 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 [ Time Frame: First dose date up to 35 months ]
- Phase 2 Cohort 1: PFS as Determined by Investigator Assessment Using RECIST Version 1.1 [ Time Frame: 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 [ Time Frame: 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: Objective Response Rate (ORR) as Determined by Investigator Assessment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Up to 35 months ]OS is defined as time from date of randomization to death from any cause.
- Magrolimab Concentration Versus Time [ Time Frame: Up to end of treatment (approximately 35 months) ]
- Antidrug Antibodies (ADA) to Magrolimab [ Time Frame: Up to end of treatment (approximately 35 months) ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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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
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High-dose systemic corticosteroids (≥ 20 mg of prednisone or its equivalent) are not allowed within 2 weeks of Cycle 1 Day 1
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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
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Note: Other protocol defined Inclusion/Exclusion criteria may apply.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04958785
| Contact: Gilead Clinical Study Information Center | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
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| Study Director: | Gilead Study Director | Gilead Sciences |
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT04958785 |
| Other Study ID Numbers: |
GS-US-586-6144 2021-001074-27 ( EudraCT Number ) |
| First Posted: | July 12, 2021 Key Record Dates |
| Last Update Posted: | May 16, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Breast Neoplasms Triple Negative Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Albumin-Bound Paclitaxel Magrolimab Sacituzumab govitecan |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Immunoconjugates Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Immunological |