JPWO2020025532A5 - - Google Patents

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JPWO2020025532A5
JPWO2020025532A5 JP2021504257A JP2021504257A JPWO2020025532A5 JP WO2020025532 A5 JPWO2020025532 A5 JP WO2020025532A5 JP 2021504257 A JP2021504257 A JP 2021504257A JP 2021504257 A JP2021504257 A JP 2021504257A JP WO2020025532 A5 JPWO2020025532 A5 JP WO2020025532A5
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bispecific antibody
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antibody construct
leukemia
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Priority claimed from PCT/EP2019/070343 external-priority patent/WO2020025532A1/en
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骨髄性白血病の治療のための方法における使用のための、ＣＤ３３に特異的に結合する第１の結合ドメイン及びＣＤ３に特異的に結合する第２の結合ドメインを含む二重特異性抗体コンストラクトであって、前記二重特異性抗体コンストラクトの前記第１の結合ドメインは、配列番号９４～９６及び９８～１００の６つのＣＤＲの群を含み、前記二重特異性抗体コンストラクトの前記第２の結合ドメインは、配列番号２０２～２０７の６つのＣＤＲの群を含み、少なくとも１つの治療サイクルにおいて投与され、前記少なくとも１つの治療サイクルは、少なくとも２つの投与段階を適用する、少なくとも３つの異なる投与量における前記二重特異性抗体コンストラクトの少なくとも１５日の投与を含み、任意選択により、その後、前記コンストラクトの投与を伴わない期間が続き、
前記二重特異性抗体コンストラクトは、以下の工程：
（ａ）前記二重特異性抗体コンストラクトの１日あたり少なくとも５μｇの第１の投与量の投与、ここで、前記第１の投与量の期間は、１～４日であり、続いて
（ｂ）前記二重特異性抗体コンストラクトの１日あたり少なくとも３０μｇの第２の投与量の投与、ここで、前記第２の投与量は、前記第１の投与量を超え、前記第２の投与量の期間は、２～５日であり、続いて
（ｃ）前記二重特異性抗体コンストラクトの１日あたり少なくとも２４０μｇの第３の投与量の投与、ここで、前記第３の投与量は、前記第２の投与量を超える、任意選択により、続いて
（ｄ）前記二重特異性抗体コンストラクトの第４の投与量の投与、ここで、前記任意選択による第４の投与量は、前記第３の投与量を超え、工程（ｃ）における前記第３の投与量の期間及び工程（ｄ）における任意選択による第４の投与量の期間は併せて、７～５２日である、
を含むスケジュールに従って前記１つ以上の治療サイクルの少なくとも１つで投与される、二重特異性抗体コンストラクト。 A bispecific antibody construct comprising a first binding domain that specifically binds CD33 and a second binding domain that specifically binds CD3 for use in a method for the treatment of myeloid leukemia wherein said first binding domain of said bispecific antibody construct comprises a group of six CDRs of SEQ ID NOs: 94-96 and 98-100, and said second binding domain of said bispecific antibody construct comprises at least 3 different doses, wherein the domain comprises a group of 6 CDRs of SEQ ID NOs: 202-207 and is administered in at least one treatment cycle, said at least one treatment cycle applying at least 2 administration steps for at least 15 days , optionally followed by a period without administration of said construct,
Said bispecific antibody construct comprises the following steps:
(a) administering a first dose of at least 5 μg per day of said bispecific antibody construct , wherein said first dose duration is 1-4 days, followed by (b) administration of a second dose of at least 30 μg per day of said bispecific antibody construct , wherein said second dose exceeds said first dose and for the duration of said second dose is 2-5 days, followed by (c) administration of a third dose of at least 240 μg per day of said bispecific antibody construct , wherein said third dose comprises said second optionally followed by (d) administration of a fourth dose of said bispecific antibody construct , wherein said optional fourth dose is greater than said third dose of over the dose, the duration of the third dose in step (c) and the duration of the optional fourth dose in step (d) together is 7 to 52 days;
A bispecific antibody construct administered in at least one of said one or more treatment cycles according to a schedule comprising: １つの治療サイクルにおいて前記二重特異性抗体コンストラクトを投与する期間は、２８～５６日である、請求項１に記載の使用のための二重特異性抗体コンストラクト。 The bispecific antibody construct for use according to claim 1, wherein the duration of administration of said bispecific antibody construct in one treatment cycle is 28-56 days. １つの治療サイクルにおける前記二重特異性抗体コンストラクトを投与する期間は、２８日である、請求項１に記載の使用のための二重特異性抗体コンストラクト。2. A bispecific antibody construct for use according to claim 1, wherein the duration of administration of said bispecific antibody construct in one treatment cycle is 28 days. 工程（ａ）における前記第１の投与量は、１日あたり５～２０μｇの範囲であり、工程（ｂ）における前記第２の投与量は、１日あたり３０～２４０μｇの範囲であり、且つ工程（ｃ）における前記第３の投与量及び工程（ｄ）における前記任意選択による第４の投与量は、１日あたり２４０～１５００μｇの範囲である、請求項１～３のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 wherein said first dosage in step (a) ranges from 5 to 20 μg per day, said second dosage in step (b) ranges from 30 to 240 μg per day , and 4. The method of any one of claims 1-3, wherein the third dose in (c) and the optional fourth dose in step (d) range from 240 to 1500 μg per day. Bispecific antibody constructs for use in 工程（ａ）における前記第１の投与量は、１日あたり１０μｇであり、工程（ｂ）における前記第２の投与量は、１日あたり６０～２４０μｇであり、工程（ｃ）における前記第３の投与量及び工程（ｄ）における前記第４の投与量は、１日あたり２４０～９６０μｇの範囲である、請求項１～３のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。The first dosage in step (a) is 10 μg per day, the second dosage in step (b) is 60-240 μg per day, and the third dosage in step (c) is and said fourth dose in step (d) ranges from 240 to 960 μg per day. construct. 工程（ａ）における前記第１の投与量の投与の期間は、２又は３日であり、工程（ｂ）における前記第２の投与量の投与の期間は、２又は３日であり、且つ工程（ｃ）における前記第３の投与量及び工程（ｄ）における前記任意選択による第４の投与量の投与の期間は併せて、１４～５２日である、請求項１に記載の使用のための二重特異性抗体コンストラクト。 The period of administration of the first dose in step (a) is 2 or 3 days, the period of administration of the second dose in step (b) is 2 or 3 days, and The use according to claim 1, wherein the duration of administration of said third dose in (c) and said optional fourth dose in step (d) together is 14 to 52 days . bispecific antibody construct. 工程（ｃ）における前記第３の投与量の期間及び工程（ｄ）における前記第４の投与量の期間は併せて、２２、２３又は５２日である、請求項１に記載の使用のための二重特異的抗体コンストラクト。2. For use according to claim 1, wherein the duration of the third dosage in step (c) and the duration of the fourth dosage in step (d) are together 22, 23 or 52 days. Bispecific antibody construct. 前記骨髄性白血病の前記治療は、２、３、４、５、６又は７つの治療サイクルを含み、少なくとも１、２、３、４、５、６又は７つの治療サイクルは、１４日を超える二重特異性抗体コンストラクト投与を含む、請求項２～６のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 said treatment of said myeloid leukemia comprises 2 , 3, 4, 5, 6 or 7 treatment cycles, wherein at least 1, 2, 3, 4, 5, 6 or 7 treatment cycles are more than 14 days A bispecific antibody construct for use according to any one of claims 2 to 6, comprising bispecific antibody construct administration. 少なくとも１つの治療サイクル後、前記コンストラクトの投与を伴わない期間、治療を伴わない少なくとも１、２、３、４、５、６、７、８、９、１０、１１、１２、１３又は１４日が続く、請求項２～８のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 After at least one treatment cycle, a period of time without administration of said construct, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days without treatment. A bispecific antibody construct for use according to any one of claims 2 to 8, followed by. 少なくとも１つの治療サイクル後、前記コンストラクトの投与を伴わない期間が続かない、請求項２～８のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 Bispecific antibody construct for use according to any one of claims 2 to 8, wherein at least one treatment cycle is followed by no period without administration of said construct. 前記治療の第１のサイクルのみは、工程（ａ）による前記投与を含む一方、その後のサイクルは、工程（ｂ）による前記用量で開始する、請求項８～１０のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 11. A method according to any one of claims 8 to 10, wherein only the first cycle of treatment comprises said administration according to step (a), while subsequent cycles start with said dose according to step (b). Bispecific antibody constructs for use. 一本鎖二重特異性抗体コンストラクトである、請求項１～１１のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 Bispecific antibody construct for use according to any one of claims 1 to 11, which is a single chain bispecific antibody construct. 配列番号１０４及び１０８からなる群から選択されるアミノ酸配列を含む一本鎖コンストラクトである、請求項１～１１のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 Bispecific antibody for use according to any one of claims 1 to 11, which is a single-chain construct comprising an amino acid sequence selected from the group consisting of SEQ ID NO : 104 and 108 construct. ＰＤ－１阻害剤、ＰＤＬ－１阻害剤並びに／又はヒストンデアセチラーゼ（ＨＤＡＣ）阻害剤、ＤＮＡメチルトランスフェラーゼ（ＤＮＭＴ）Ｉ阻害剤、ヒドロキシ尿素、顆粒球コロニー刺激因子（Ｇ－ＣＳＦ）、ヒストンデメチラーゼ阻害剤及びＡＴＲＡ（全トランス型レチノイン酸）からなる群から選択される１つ以上のエピジェネティック因子と組み合わせて投与され、
（ａ）前記ＰＤ－１阻害剤、ＰＤＬ－１阻害剤及び／又は１つ以上のエピジェネティック因子は、前記二重特異性抗体コンストラクトの前記投与前に投与されるか；
（ｂ）前記ＰＤ－１阻害剤、ＰＤＬ－１阻害剤及び／又は１つ以上のエピジェネティック因子は、前記二重特異性抗体コンストラクトの前記投与後に投与されるか；又は
（ｃ）前記ＰＤ－１阻害剤、ＰＤＬ－１阻害剤及び／又は１つ以上のエピジェネティック因子並びに前記二重特異性抗体コンストラクトは、同時に投与され、
前記ＰＤ－１阻害剤、ＰＤＬ－１阻害剤及び／又は１つ以上のエピジェネティック因子は、前記二重特異性抗体コンストラクトの投与の７日前まで投与され、
前記エピジェネティック因子は、好ましくはヒドロキシ尿素である、請求項１～１３のいずれか１項に記載の使用のための二重特異性抗体コンストラクト。 PD-1 inhibitors, PDL-1 inhibitors and/or histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) I inhibitors, hydroxyurea, granulocyte colony stimulating factor (G-CSF), histone de administered in combination with one or more epigenetic factors selected from the group consisting of methylase inhibitors and ATRA (all-trans retinoic acid),
(a) is said PD-1 inhibitor, PDL-1 inhibitor and/or one or more epigenetic factors administered prior to said administration of said bispecific antibody construct;
(b) said PD-1 inhibitor, PDL-1 inhibitor and/or one or more epigenetic factors are administered after said administration of said bispecific antibody construct; or (c) said PD- 1 inhibitor, PDL-1 inhibitor and/or one or more epigenetic factors and said bispecific antibody construct are administered simultaneously ,
said PD-1 inhibitor, PDL-1 inhibitor and/or one or more epigenetic factors are administered up to 7 days prior to administration of said bispecific antibody construct ;
Bispecific antibody construct for use according to any one of claims 1 to 13, wherein said epigenetic factor is preferably hydroxyurea. 前記骨髄性白血病は、急性骨髄芽球性白血病、好ましくは再発性又は難治性急性骨髄性白血病、慢性好中球性白血病、骨髄性樹状細胞白血病、移行期慢性骨髄性白血病、急性骨髄単球性白血病、若年性骨髄単球性白血病、慢性骨髄単球性白血病、急性好塩基球性白血病、急性好酸球性白血病、慢性好酸球性白血病、急性巨核芽球性白血病、本態性血小板増加症、急性赤白血病、真性多血症、骨髄異形成症候群、急性汎骨髄性白血病、骨髄肉腫及び急性混合性白血病からなる群から選択される、請求項１～１４のいずれか一項に記載の使用のための二重特異性抗体コンストラクト。 The myeloid leukemia is acute myeloblastic leukemia, preferably relapsed or refractory acute myeloid leukemia, chronic neutrophilic leukemia, myeloid dendritic cell leukemia, transitional chronic myelogenous leukemia, acute myelomonocytic leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute basophilic leukemia, acute eosinophilic leukemia, chronic eosinophilic leukemia, acute megakaryoblastic leukemia, essential thrombocytosis Acute erythroleukemia, polycythemia vera, myelodysplastic syndrome, acute panmyelogenous leukemia, myelosarcoma and acute mixed leukemia according to any one of claims 1 to 14. Bispecific antibody constructs for use. 骨髄性白血病の治療のための医薬組成物であって、ＣＤ３３に特異的に結合する第１の結合ドメイン及びＣＤ３に特異的に結合する第２の結合ドメインを含む二重特異性抗体コンストラクトを含み、ここで、前記二重特異性抗体コンストラクトの前記第１の結合ドメインは、配列番号９４～９６及び９８～１００の６つのＣＤＲの群を含み、前記二重特異性抗体コンストラクトの前記第２の結合ドメインは、配列番号２０２～２０７の６つのＣＤＲの群を含み、前記医薬組成物は、少なくとも１つの治療サイクルにおいて投与され、前記少なくとも１つの治療サイクルは、少なくとも２つの投与段階を適用する、少なくとも３つの異なる投与量における前記医薬組成物の少なくとも１５日の投与を含み、
前記医薬組成物は、以下の工程：
（ａ）前記二重特異性抗体コンストラクトの１日あたり少なくとも５μｇの第１の投与量の投与、続いて
（ｂ）前記二重特異性抗体コンストラクトの１日あたり少なくとも３０μｇの第２の投与量の投与、ここで、前記第２の投与量の投与期間は、２～５日であり、前記第２の投与量は、前記第１の投与量を超える、続いて
（ｃ）前記二重特異性抗体コンストラクトの１日あたり少なくとも２４０μｇの第３の投与量の投与、ここで、前記第３の投与量は、前記第２の投与量を超える、任意選択により、続いて
（ｄ）前記二重特異性抗体コンストラクトの第４の投与量の投与、ここで、前記任意選択による第４の投与量は、前記第３の投与量を超え、任意選択により、その後、前記コンストラクトの投与を伴わない期間が続き、工程（ｃ）における前記第３の投与量の期間及び工程（ｄ）における任意選択の第４の投与期間は併せて、７～５２日である、
を含むスケジュールに従って１つの治療サイクルで投与される、医薬組成物。 A pharmaceutical composition for the treatment of myeloid leukemia, comprising: a bispecific antibody construct comprising a first binding domain that specifically binds CD33 and a second binding domain that specifically binds CD3 wherein said first binding domain of said bispecific antibody construct comprises a group of six CDRs of SEQ ID NOs: 94-96 and 98-100, and said The second binding domain comprises a group of six CDRs of SEQ ID NOS: 202-207, and said pharmaceutical composition is administered in at least one treatment cycle, said at least one treatment cycle comprising at least two administration steps. at least 15 days of administration of said pharmaceutical composition in at least 3 different dosages,
Said pharmaceutical composition comprises the steps of:
(a) administering a first dose of at least 5 μg per day of said bispecific antibody construct followed by (b) administering a second dose of at least 30 μg per day of said bispecific antibody construct; administration , wherein the duration of administration of said second dose is 2-5 days, and said second dose exceeds said first dose, followed by (c) said bispecific administration of a third dose of at least 240 μg per day of the antibody construct , wherein said third dose exceeds said second dose, optionally followed by (d) said double administration of a fourth dose of a specific antibody construct , wherein said optional fourth dose exceeds said third dose, optionally followed by a period of time without administration of said construct followed by said third dosage period in step (c) and the optional fourth dosage period in step (d) together being 7 to 52 days.
A pharmaceutical composition administered in one treatment cycle according to a schedule comprising １つの治療サイクルにおいて前記二重特異性抗体コンストラクトを投与する期間は、１５～６０日、好ましくは２８～５６日、より好ましくは２８日である、請求項１６に記載の医薬組成物。 The pharmaceutical composition according to claim 16, wherein the duration of administration of said bispecific antibody construct in one treatment cycle is 15-60 days, preferably 28-56 days, more preferably 28 days. . 工程（ａ）における前記第１の投与量は、１日あたり５～２０μｇの範囲、より好ましくは１日あたり１０μｇであり、工程（ｂ）における前記第２の投与量は、１日あたり３０～２４０μｇの範囲、好ましくは１日あたり６０又は２４０μｇであり、且つ工程（ｃ）における前記第３の投与量及び任意選択による工程（ｄ）における前記任意選択による第４の投与量は、１日あたり１２０～１５００μｇ、好ましくは１日あたり２４０～９６０μｇ、より好ましくは１日あたり４８０～９６０μｇの範囲である、請求項１６又は１７に記載の医薬組成物。 The first dosage in step (a) is in the range of 5-20 μg per day, more preferably 10 μg per day, and the second dosage in step (b) is in the range of 30-20 μg per day. in the range of 240 μg, preferably 60 or 240 μg per day, and said third dose in step (c) and said optional fourth dose in step (d) are: Pharmaceutical composition according to claim 16 or 17, in the range 120-1500 μg, preferably 240-960 μg per day, more preferably 480-960 μg per day. 工程（ａ）における前記第１の投与量の投与の期間は、２又は３日であり、工程（ｂ）における前記第２の投与量の投与の期間は、２又は３日であり、且つ工程（ｃ）及び任意選択による工程（ｄ）における前記第３の用量及び前記任意選択による第４の投与量の投与の期間は、１４～２３日、より好ましくは２２、２３、５０又は５２日である、請求項１６～１８のいずれか一項に記載の医薬組成物。 The period of administration of the first dose in step (a) is 2 or 3 days, the period of administration of the second dose in step (b) is 2 or 3 days, and The duration of administration of said third dose and said optional fourth dose in (c) and optionally step (d) is 1 4-23 days, more preferably 22, 23, 50 or 52 days The pharmaceutical composition according to any one of claims 16 to 18, which is 前記骨髄性白血病の前記治療は、２つ以上の治療サイクル、好ましくは２、３、４、５、６又は７つの治療サイクルを含み、少なくとも１、２、３、４、５、６又は７つの治療サイクルは、１４日を超える二重特異性抗体コンストラクト投与を含む、請求項１６～１９のいずれか一項に記載の医薬組成物。 said treatment of said myeloid leukemia comprises two or more treatment cycles, preferably 2, 3, 4, 5, 6 or 7 treatment cycles, wherein at least 1, 2, 3, 4, 5, 6 or 7 20. The pharmaceutical composition according to any one of claims 16-19, wherein the treatment cycle comprises administration of the bispecific antibody construct for more than 14 days. 前記治療後、前記二重特異性抗体コンストラクトの投与を伴わない期間、好ましくは治療を伴わない少なくとも１、２、３、４、５、６、７、８、９、１０、１１、１２、１３又は１４日が続く、請求項１６～２０のいずれか一項に記載の医薬組成物。 a period of time after said treatment without administration of said bispecific antibody construct, preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 without treatment or lasting 14 days. 前記治療後、前記二重特異性抗体コンストラクトの投与を伴わない少なくとも１４日の期間が続く、請求項１６～２０のいずれか一項に記載の医薬組成物。 The pharmaceutical composition of any one of claims 16-20, wherein said treatment is followed by a period of at least 14 days without administration of said bispecific antibody construct. 前記治療の第１のサイクルのみは、工程（ａ）による前記投与を含む一方、その後のサイクルは、工程（ｂ）による前記用量で開始する、請求項１６～２２のいずれか一項に記載の医薬組成物。 23. A method according to any one of claims 16 to 22, wherein only the first cycle of treatment comprises said administration according to step (a), while subsequent cycles start with said dose according to step (b). pharmaceutical composition. 前記コンストラクトは、一本鎖二重特異性抗体コンストラクトである、請求項１６～２２のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 16-22, wherein said construct is a single chain bispecific antibody construct. 前記二重特異性抗体コンストラクトは、配列番号１８、１９、２０、３０、３１、３２、４２、４３、４４、５４、５５、５６、６６、６７、６８、７８、７９、８０、９０、９１、９２、１０２、１０３、１０４、１０５、１０６、１０７及び１０８からなる群から選択される、好ましくは配列番号１０４、１０５、１０６、１０７及び１０８、より好ましくは配列番号１０４からなる群から選択されるアミノ酸配列を含む一本鎖コンストラクトである、請求項１６～２４のいずれか一項に記載の医薬組成物。 Said bispecific antibody constructs have the , 92, 102, 103, 104, 105, 106, 107 and 108, preferably SEQ ID NO: 104, 105, 106, 107 and 108, more preferably SEQ ID NO: 104 The pharmaceutical composition according to any one of claims 16 to 24, which is a single-chain construct comprising the amino acid sequence of 少なくとも１つのＰＤ－１阻害剤、ＰＤＬ－１阻害剤並びに／又はヒストンデアセチラーゼ（ＨＤＡＣ）阻害剤、ＤＮＡメチルトランスフェラーゼ（ＤＮＭＴ）Ｉ阻害剤、ヒドロキシ尿素、顆粒球コロニー刺激因子（Ｇ－ＣＳＦ）、ヒストンデメチラーゼ阻害剤及びＡＴＲＡ（全トランス型レチノイン酸）からなる群から選択される１つ以上のエピジェネティック因子を投与することをさらに含み、前記少なくとも１つのＰＤ－１阻害剤、ＰＤＬ－１阻害剤及び／又は１つ以上のエピジェネティック因子は、
（ａ）前記二重特異性抗体コンストラクトの前記投与前；
（ｂ）前記二重特異性抗体コンストラクトの前記投与後；又は
（ｃ）前記二重特異性抗体コンストラクトと同時に投与される、請求項１６～２５のいずれか一項に記載の医薬組成物。 at least one PD-1 inhibitor, PDL-1 inhibitor and/or histone deacetylase (HDAC) inhibitor, DNA methyltransferase (DNMT) I inhibitor, hydroxyurea, granulocyte colony stimulating factor (G-CSF) , histone demethylase inhibitors and ATRA (all-trans-retinoic acid), wherein said at least one PD-1 inhibitor, PDL-1 The inhibitor and/or one or more epigenetic factors are
(a) prior to said administration of said bispecific antibody construct;
(b) after said administration of said bispecific antibody construct; or (c) administered simultaneously with said bispecific antibody construct . 前記１つのＰＤ－１阻害剤、ＰＤＬ－１阻害剤又は１つ以上のエピジェネティック因子は、前記二重特異性抗体コンストラクトの投与の７日前まで投与される、請求項１６～２６のいずれか一項に記載の医薬組成物。 27. Any one of claims 16-26, wherein said one PD-1 inhibitor, PDL-1 inhibitor or one or more epigenetic factors is administered up to 7 days prior to administration of said bispecific antibody construct. The pharmaceutical composition according to the paragraph. 前記エピジェネティック因子は、ヒドロキシ尿素である、請求項１６～２７のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 16-27, wherein said epigenetic factor is hydroxyurea. 前記骨髄性白血病は、急性骨髄芽球性白血病、好ましくは再発性又は難治性急性骨髄性白血病、慢性好中球性白血病、骨髄性樹状細胞白血病、移行期慢性骨髄性白血病、急性骨髄単球性白血病、若年性骨髄単球性白血病、慢性骨髄単球性白血病、急性好塩基球性白血病、急性好酸球性白血病、慢性好酸球性白血病、急性巨核芽球性白血病、本態性血小板増加症、急性赤白血病、真性多血症、骨髄異形成症候群、急性汎骨髄性白血病、骨髄肉腫及び急性混合性白血病、急性混合型白血病からなる群から選択される、請求項１６～２８のいずれか一項に記載の医薬組成物。 The myeloid leukemia is acute myeloblastic leukemia, preferably relapsed or refractory acute myeloid leukemia, chronic neutrophilic leukemia, myeloid dendritic cell leukemia, transitional chronic myelogenous leukemia, acute myelomonocytic leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute basophilic leukemia, acute eosinophilic leukemia, chronic eosinophilic leukemia, acute megakaryoblastic leukemia, essential thrombocytosis acute erythroleukemia, polycythemia vera, myelodysplastic syndrome, acute panmyelogenous leukemia, myelosarcoma and acute mixed leukemia, acute mixed leukemia. The pharmaceutical composition according to item 1.
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