MC# 21-24 - A Phase II, Multi-Arm Study of Magrolimab in Patients with Solid Tumors

  • Agent(s): Magrolimab
  • Disease Type(s): Bladder, Lung-NSCLC, Lung-SCLC
  • Phase(s): II
  • Drug Classification(s): Targeted Therapy, Monoclonal Antibody
  • Molecular Target(s): CD47

Mechanism of Action

Magrolimab selectively binds to CD47 expressed on tumor cells and blocks the interaction of CD47 with its ligand signal regulatory protein alpha (SIRPa), a protein expressed on phagocytic cells.  This prevents CD47/SIRPa-mediated signaling, allows the activation of macrophages, through the induction of pro-phagocytic signaling mediated by calreticulin, which is specifically expressed on the surface of tumor cells, and results in specific tumor cell phagocytosis.  In addition, blocking CD47 signaling activates an anti-tumor T-lymphocyte immune response and T-mediated cell killing.

Purpose

In this study, the sponsor and investigators want to learn:

  • The initial phase (safety run-in) is to confirm a safe dose of Magrolimab in combination with Docetaxel
  • The second part (phase 2) is to see if Magrolimab in combination with Docetaxel is effective in treating various types of solid tumors
  • Other purposes of this study include determining the quantity of Magrolimab in the blood and the side effects these drugs have on the body
Inclusion Criteria
  1. Patient has provided informed consent
  2. Patient is willing and able to comply with clinic visits and procedures outlined in the study protocol
  3. Male or female ≥ 18 years of age
  4. Patients must have an ECOG performance status of ≤ 2
  5. Laboratory measurements, blood counts:
    1. Hemoglobin ≥ 9.5 g/dL.  Red blood cell transfusions are permitted to meet the hemoglobin inclusion criteria, within limits set per exclusion criterion 4.
    2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/mL
    3. Platelets ≥ 100 x 109/mL
  6. Laboratory measurements, renal function:
    1. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or if elevated, a calculated glomerular filtration rate > 40 mL/min/1.73m²
  7. Adequate liver function, as demonstrated by:
    1. AST ≤ 1.5 x ULN
    2. ALT ≤ 1.5 x ULN
    3. Bilirubin ≤ 1.25 x ULN, or ≤ 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or genetic equivalent
  8. Pretreatment blood cross-match completed
  9. Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception
  10. Measurable disease according to 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.
  11. Patients must be willing to provide baseline tumor tissue from a core or excisional biopsy (fine needle aspirate is not adequate).  A newly obtained biopsy (within 90 days prior to study treatment start) is strongly preferred, but an archival sample is acceptable if obtained within 6 months prior to enrollment.  Patients will also be requested to consent to a mandatory on-treatment tumor biopsy unless not feasible as determined by the investigator and discussed with the sponsor.

Cohort-specific Inclusion Criteria

Patients need to fulfill the following cohort-specific criteria, in addition to satisfying the inclusion criteria for all patients:

  1. Safety Run-in Cohort 1: Patients with metastatic advanced solid tumors who have had at least 1 prior line of systemic anticancer therapy (mNSCLC and mSCLC) in a locally advanced/metastatic setting, or 2 prior lines of systemic anticancer therapy (mUC) in a locally advanced/metastatic setting, and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting
  2. Phase 2 Cohort 1a (mNSCLC): Patients with NSCLC who have had treatment with platinum-based chemotherapy and/or immune checkpoint inhibitor therapy in a locally advanced/metastatic setting are eligible.  At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed.  Patients treated with  a taxane within 12 months or patients refractory to prior taxane treatment are excluded.  Patients who were treated for EGFR, ROS1, ALK, NTRK, or MET exon 14 genomic alterations are excluded.
  3. Phase 2 Cohort 1b (mUC): Patients with UC who have had prior treatment with systemic chemotherapy and/or immune checkpoint inhibitor therapy in a locally advanced/metastatic setting are eligible.  At least 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are required and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed.  Patients treated with a taxane within 12 months or patients refractory to prior taxane treatment are excluded.
  4. Phase 2 Cohort 1c (mSCLC): Patients with SCLC who have had prior treatment with platinum-based chemotherapy with or without immunotherapy are eligible.  At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed.  Patients treated with a taxane within 12 months or patients refractory to prior taxane treatment are excluded.
Exclusion Criteria
  1. Positive serum pregnancy test
  2. Breastfeeding female
  3. Active CNS disease.  Patients with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who are off corticosteroids for at least 4 weeks) are allowed.
  4. Red blood cell 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.
  5. History of hemolytic anemia, autoimmune thrombocytopenia or Evans syndrome in the last 3 months
  6. Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
  7. Prior treatment with CD47 or SIRPα-targeting agents
  8. Current participation in another interventional clinical trial
  9. Known inherited or acquired bleeding disorders
  10. 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.
  11. 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 3 years
  12. Known active or chronic hepatitis B or C infection or human immunodeficiency virus infection in medical history
  13. Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted.  NOTE: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone releasing hormone (LHRH) agonists for prostate or breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappaB ligand (RANKL) 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.

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://www.clinicaltrials.gov/ct2/show/NCT04827576

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Re: MC# 21-24