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

Gilead Sciences

Status and phase: Active, not recruiting; Phase 2

Conditions: Triple-Negative Breast Cancer

Treatments: Drug: Sacituzumab Govitecan-hziy; Drug: Magrolimab; Drug: Nab-Paclitaxel; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04958785

GS-US-586-6144

2021-001074-27 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 92 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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92 participants in 5 patient groups

Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Nab-Paclitaxel

Drug: Magrolimab

Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Nab-Paclitaxel

Drug: Magrolimab

Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel

Active Comparator group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Nab-Paclitaxel

Drug: Magrolimab

Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan

Experimental group

Description:

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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Drug: Magrolimab

Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan

Experimental group

Description:

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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Drug: Magrolimab