magrolimab monotherapy or magrolimab in combination with azacitidine in participants with hematological malignancies

Conditions: Hematological Malignancies

Summary: the primary objectives of this study are: * to confirm the safety and tolerability of magrolimab monotherapy in a relapsed/refractory (r/r) acute myeloid leukemia (aml) and myelodysplastic syndrome (mds) population, and of magrolimab in combination with azacitidine in previously untreated participants with aml or mds and participants with r/r aml and mds * to evaluate the efficacy of magrolimab monotherapy in r/r aml/mds, and of magrolimab in combination with azacitidine in previously untreated participants with aml/mds, or r/r aml/mds as measured by complete remission (cr) rate for participants with aml and higher-risk mds, and duration of complete response for participants with aml and higher-risk mds, and duration of cr for participants with aml and higher-risk mds * to evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or combination with azacitidine in low-risk mds participants as measured by red blood cell (rbc) transfusion independence rate


Eligibility criteria:
key inclusion criteria: * meets the criteria below for the appropriate cohort: * relapsed/refractory cohorts: pathologically confirmed relapsed or refractory (primary refractory and/or relapsed refractory) acute myeloid leukemia (aml) or confirmed intermediate, high, or very high risk myelodysplastic syndromes (mds) that is relapsed, refractory or intolerant to conventional therapy. * treatment-naive/unfit cohorts: previously untreated individuals with histological confirmation of aml who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen; or previously untreated individuals with intermediate, high, or very high risk mds. prior and concurrent therapy with hydroxyurea, oral etoposide, erythroid and/or myeloid growth factors is allowed. * rollover cohort: individuals on active magrolimab therapy on the phase 1 aml (sci-cd47-002; nct02678338) trial who are deriving clinical benefit by investigator assessment. * rbc transfusion dependent low risk mds cohort: transfusion-dependent mds individuals who are very low or low risk by revised international prognostic scoring system (ipss-r) with previous treatment with an erythroid stimulating agent or lenalidomide. * white blood cell (wbc) count ≤ 20 x 10\^3/mcl * adequate performance status and hematological, liver, and kidney function. key exclusion criteria: * prior treatment with cluster of differentiation 47 (cd47) or signal regulatory protein alpha (sirpα) targeting agents (with exception of magrolimab for individuals in the rollover cohort). * treatment-naive/unfit cohorts only: any prior anti-leukemic therapy (excluding hydroxyurea or oral etoposide), prior treatment with hypomethylating agents and/or low dose cytarabine. * acute promyelocytic leukemia. * known inherited or acquired bleeding disorders. * previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (gvhd), or requiring transplant-related immunosuppression. * clinical suspicion of active central nervous system (cns) involvement by leukemia. * known active or chronic hepatitis b or c infection or hiv. * pregnancy or active breastfeeding. note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: cd47