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

Phase 2TerminatedNCT04958785

Gilead Sciences92 enrolled

Overview

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 participants with non-surgically removable locally advanced or metastatic triple-negative breast cancer. 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). This study in the Phase 2 Cohort 1 also compares 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. This study in the Phase 2 Cohort 2 also evaluates the efficacy of magrolimab in combination with sacituzumab govitecan as determined by confirmed objective response rate (ORR) by investigator assessment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Triple-Negative Breast Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion criteria: * Adequate performance status, hematologic, renal and liver function. * Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1 * Cohort 1: Individuals with previously untreated with systemic therapy for unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) that are considered programmed cell death ligand 1 (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 central nervous system (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. * Red blood cell (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 cluster of differentiation 47 (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 adverse events (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.

Locations (45)

Mayo Clinic

Phoenix, Arizona, United States

Women's Cancer Care

Fresno, California, United States

Providence Medical Foundation

Fullerton, California, United States

University of California San Francisco

San Francisco, California, United States

Saint John's Cancer Institute

Santa Monica, California, United States

Outcomes

Primary Outcomes

Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)

A DLT is defined as any: * Grade 3 or higher hematologic toxicity including: * Hemolytic anemia that is medically significant, requiring hospitalization or prolongation of existing hospitalization, disabling, or limiting self-care activities of daily life. * Event meeting Hy's Law criteria: * Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation (at least 3 x ULN), AND * Treatment-emergent total bilirubin elevation (more than 2 x ULN), and absence of cholestasis (defined as alkaline phosphatase less than 2 x ULN), AND * No other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, alcohol ingestion, congestive heart failure, worsening liver metastases). * Grade 3 or higher nonhematologic toxicity that has worsened in severity from pretreatment baseline during the DLT assessment period, and in the opinion of the investigator, the AE is at least possibly related to magrolimab.

Time frame: First dose date up to 28 days (Cohort 1) and up to 21 days (Cohort 2)

Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

TEAEs are defined as any events not present prior to the study treatment, or any events already present but worsening in either intensity or frequency following exposure to the study treatment. TEAEs were any AEs with an onset date on or after the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment, or the day before initiation of subsequent anticancer therapy, whichever comes first. An AE is any untoward medical occurrence in a clinical study patient administered a study drug that does not necessarily have a causal relationship with the treatment.

Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days

Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0

Treatment-emergent laboratory abnormalities according to NCI CTCAE V5.0 are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days and prior to the day before initiation of subsequent anti-cancer therapy. Grade 1 mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening and Grade 5 death. Percentages were rounded off.

Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days

Phase 2 Cohort 1: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

PFS was defined as the time from the date of randomization until the earliest date of documented disease progression (PD), as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (KM) estimates were used in outcome measure analysis.

Time frame: Up to 107 weeks

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

ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as determined at least 4 weeks after initial documentation of response by investigator assessment per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off.

Time frame: Up to 107 weeks

Secondary Outcomes

Phase 2 Cohort 1: Confirmed ORR as Determined by Investigator Assessment Per RECIST, Version 1.1

ORR is defined as the percentage of participants who achieve a CR or PR that is confirmed at least 4 weeks after initial documentation of response, as measured by RECIST version 1.1, as determined by investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off.

Time frame: Up to 107 weeks

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. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: Up to 107 weeks

Phase 2 Cohort 1, 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 CR or PR to the earliest date of documented PD, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: Up to 107 weeks

Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs

Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days

Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI CTCAE, Version 5.0

Time frame: First dose date up to last dose date (up to 73 weeks) plus 30 days