Ensayos clínicos

Inclusion Criteria:

• Patient has provided informed consent
• Patient is willing and able to comply with clinic visits and procedures outlined in the study protocol
• Male or female, at least 18 years of age
• Patients must have an ECOG performance status of 0 or 1.
• Laboratory measurements, blood counts:
  • Hemoglobin must be ≥ 9 g/dL prior to initial dose of study treatment. Red blood cell
    (RBC) transfusions are allowed to meet hemoglobin eligibility within limits set per
    Exclusion Criterion #4 
  • Absolute neutrophil count (ANC) at least 1.5 x 10^9/L without growth factor support
    within 2 weeks of study treatment initiation
  • Platelets at least 100 x 10^9/L
• Laboratory measurements, renal function:
  • Patients must have adequate renal function as demonstrated by a creatinine clearance of at least 30 mL/min; calculated by the Cockcroft Gault formula
• Adequate liver function, as demonstrated by:
  • AST less than or equal to 2.5 x ULN or less than or equal to 5 x ULN in patients with liver metastases
  • ALT less than or equal to 2.5 x ULN or less than or equal to 5 x ULN in patients with liver metastases
  • Bilirubin less than or equal to 1.5 x ULN, or less than or equal to 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or genetic equivalent
• Pretreatment blood cross-match completed (Section 7.8.1.1)
• Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 5.
• Measurable disease according to response evaluation criteria in solid tumors (RECIST),Version 1.1. Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
• Patients must have a life expectancy of 3 months or greater, in the opinion of the investigator.

Safety Run-in Cohort 1 and Phase 2 Cohort 1
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Safety
Run-in Cohort 1 and Phase 2 Cohort 1 must fulfill the following cohort-specific inclusion
criteria:

• Patients previously untreated for unresectable locally advanced or mTNBC that is histologically or cytologically confirmed based on the most recent analyzed biopsy or other pathology specimen, defined as negative for estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) according to the most recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline (Appendix 9).
• Patients whose tumors are considered PD-L1 negative, as determined by an approved test according to local standards.
• Prior systemic treatment for neoadjuvant and/or adjuvant therapy and/or curative intent radiation therapy is permitted if completed at least 6 months prior to enrollment.

Note: Maintenance therapies are not counted as separate lines of therapy.

Safety Run-in Cohort 2 and Phase 2 Cohort 2
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Safety
Run-in Cohort 2 and Phase 2 Cohort 2 must fulfill the following cohort-specific inclusion
criterion:

• Patients with unresectable, locally advanced or mTNBC that is histologically or cytologically confirmed based on the most recent analyzed biopsy or other pathology specimen, defined as negative for ER, PR, and HER2 according to the most recent ASCO/CAP guideline (Appendix 9), who have received 1 prior line of therapy in the unresectable, locally advanced/metastatic setting. Patients must have been previously treated with a taxane in the neoadjuvant, adjuvant, or locally advanced/metastatic setting
• Patients with tumors considered positive for PD-L1 expression (as determined by an approved test according to local standards) must have received an immune checkpoint inhibitor for 1L treatment of locally advanced/metastatic disease

Exclusion Criteria:

• Positive serum pregnancy test.
• Breastfeeding female.
• Active central nervous system (CNS) disease. Patients 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.
• 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. RBC 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.
• Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
• Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha-targeting agents.
• Current participation in another interventional clinical trial.
• Known inherited or acquired bleeding disorders.
• Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV
• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients are not on active anticancer therapies and who are in complete remission for over 2 years.
• Known active or chronic hepatitis B or C infection or human immunodeficiency virus infection in medical history).
• Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted.
• Uncontrolled pleural effusion.
• Uncontrolled hypercalcemia (ionized calcium >1.5 mmol/L) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
• Uncontrolled tumor-related pain.
• Severe/serious systemic infection within 4 weeks of randomization.
• Rapid deterioration during screening prior to enrollment (eg, significant change in performance status, 20% or greater decrease in serum albumin levels or uncontrolled tumorrelated pain)
• Other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and followup
  examinations
• Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted
• Patients who have received a live vaccine within 30 days of randomization
   

Safety Run-in Cohort 1 and Phase 2 Cohort 1
Patients who meet the following exclusion criterion are not eligible to be enrolled into Safety
Run-in Cohort 1 or Phase 2 Cohort 1:

• 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.

NOTE: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormonereleasing
hormone agonists for breast cancer, and treatment with bisphosphonates and receptor
activator of nuclear factor kappa B ligand inhibitors are not criteria for exclusion. There is no
required minimum washout period for these therapies. Patients should be recovered from the
effects of radiation.

Safety Run-in Cohort 2 and Phase 2 Cohort 2
Patients who meet any of the following exclusion criteria are not eligible to be enrolled into
Safety Run-in Cohort 2 or Phase 2 Cohort 2:

• Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and patients with a history of bowel obstruction or gastrointestinal perforation within 6 months of enrollment
• Patients 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: patients with any grade neuropathy or alopecia are an exception to this criterion and will qualify for the study
  • Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

NOTE: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormonereleasing hormone agonists for breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa B ligand inhibitors are not criteria for exclusion. There is no required minimum washout period for these therapies. Patients should be recovered from the effects of radiation.

Eligibility last updated 2/18/22. Questions regarding updates should be directed to the study team contact.