JP7312706B2 - 血液悪性腫瘍に対するcd47標的化治療のための投与パラメータ - Google Patents
血液悪性腫瘍に対するcd47標的化治療のための投与パラメータ Download PDFInfo
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- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229940055760 yervoy Drugs 0.000 description 1
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Description
(項目1)
抗CD47因子を用いて血液悪性腫瘍を有する患者を治療するための方法であって、
血液悪性腫瘍を患う患者が治療のための循環腫瘍細胞の安全レベルを有していることを確認することと、
前記患者に由来する骨髄芽球において約80%超の受容体占有率が達成される治療用量に到達する漸増用量レジメンで抗CD47因子を投与することと、
前記血液悪性腫瘍を治療するために十分な期間にわたり前記治療用量を投与することと
を含む、用量及び漸増スケジュールで抗CD47因子のレジメンを実施すること、
を含む、方法。
(項目2)
循環腫瘍細胞の安全レベルを有していないことが確認された患者は、循環腫瘍細胞の安全レベルを達成するために、初期の治療用量以下の抗CD47因子を投与することにより、または、細胞減少療法を実施することにより、治療される、項目1に記載の方法。
(項目3)
前記血液悪性腫瘍は白血病である、項目1または項目2に記載の方法。
(項目4)
前記血液悪性腫瘍は急性骨髄性白血病(AML)である、項目3に記載の方法。
(項目5)
前記抗CD47因子はCD47に特異的に結合する、項目1から項目4のいずれか一項に記載の方法。
(項目6)
前記抗CD47因子は抗体である、項目1から項目4のいずれか一項に記載の方法。
(項目7)
前記抗体はCD47に特異的に結合する抗体である、項目6に記載の方法。
(項目8)
前記循環腫瘍細胞の安全レベルは約10×10 9 循環芽球/リットル未満である、項目1から項目7のいずれか一項に記載の方法。
(項目9)
前記細胞減少療法はヒドロキシウレアの投与を含む、項目2から項目8のいずれか一項に記載の方法。
(項目10)
漸増用量レジメンで抗CD47因子を投与する前に、前記患者の循環芽球または白血球を測定する過程を更に含む、項目1から項目9のいずれか一項に記載の方法。
(項目11)
骨髄における受容体占有率を測定する過程を更に含む、項目1から項目10のいずれか一項に記載の方法。
(項目12)
前記抗CD47因子の初期用量は約1mg/kg/投与である、項目1から項目11のいずれか一項に記載の方法。
(項目13)
用量は約1~30mg/kg/投与分漸増される、項目12に記載の方法。
(項目14)
用量は週に2回から隔週で漸増される、項目13に記載の方法。
(項目15)
前記抗CD47因子は週に2回から隔週で投与される、項目13または項目14に記載の方法。
(項目16)
追加の治療因子の投与を更に含む、項目1から項目15のいずれか一項に記載の方法。
(項目17)
前記追加の治療因子は脱メチル化因子である、項目16に記載の方法。
(項目18)
前記追加の治療因子は、化学療法剤、腫瘍免疫療法薬、腫瘍標的薬、食細胞の活性化、増殖または局在化を促進する生物学的因子、移植、輸血、ロイコフェレーシス、またはエリスロポエチン刺激因子のうちの1種または複数種である、項目16に記載の方法。
本発明は、添付図面と関連させて読解する場合、以下の発明を実施するための形態から最も理解される。一般的な慣習に従い、図中の様々な形状は縮尺に従っていないことを強調しておく。別の見方をすれば、様々な形状の寸法は、分かりやすくするために適宜伸びたり縮んだりしている。図面中に含まれるものは以下の図である。
「と組み合わせて」、「組み合わせ治療」及び「組み合わせ生成物」とは、特定の実施形態では、本明細書に記載の因子を患者に同時投与することを意味する。組み合わせて投与する際、それぞれの成分を、同時または連続的に、任意の順番で、異なる時点で、投与してもよい。それゆえ、それぞれの成分を、別々にではあるが所望の治療効果がもたらされるような十分に近い時間間隔で投与してもよい。
治療有効用量の抗CD47因子の投与は、臨床的に有効な期間内に治療レベルを達成しつつ安全な用量漸増をもたらすスケジュールで提供される。本方法は、クリアランス、漸増及び維持の過程を含んでいてもよい。一実施形態では、投与レジメンでは、その後の治療のための循環腫瘍細胞の安全レベルを達成するために、初期の(i)治療用量以下の抗CD47因子を投与するか、または、(ii)細胞減少療法を実施し(クリアランス)、治療用量に到達するまで抗CD47因子の用量を漸増させ(漸増)、患者の骨髄における腫瘍細胞を減少させるために十分な期間にわたり治療用量を維持する(維持)。
本方法に用いるキットも提供する。本キットは抗CD47因子を含む。一部の実施形態では、抗CD47因子は、投与剤形(例えば、治療に有効な投与剤形)で提供される。一部の実施形態では、抗CD47因子は、2種またはそれ以上の異なる投与剤形(例えば、2種またはそれ以上の異なる治療に有効な投与剤形)で提供される。キットに関し、プライマー因子及び/または抗CD47因子は、任意の簡便な包装(スティックパックまたはドーズパックなど)に入った液体または固体の形態で提供されてもよい。
CD47は、ヒト急性骨髄性白血病(AML)幹細胞及びその他のがん細胞上に高発現している。CD47は、ヒトマクロファージによるがん細胞の貪食作用を阻害する。CD47を遮断することにより、マクロファージが貪食作用を介してAMLを除去することができるようになる。それゆえ、CD47は治療抗体の標的である。CD47結合因子は、白血病及びその他のがん細胞、またはその他の疾患細胞の除去をもたらす。高負荷の循環疾患細胞、例えば、循環白血病またはリンパ腫細胞を対象が有している場合、CD47結合因子は、凝集及び/または溶解だけでなく、CD47標的化治療における場合により命にかかわる毒性につながり得る、疾患細胞におけるその他の細胞の殺傷及び除去も引き起こす場合がある。それゆえ、急性の命にかかわる副作用を予防する投与戦略が求められている。本発明者らは、CD47標的化治療薬の用量を徐々に増加させて循環系病変の負荷を軽減することによってこれらの毒性を予防する、対象内用量漸増戦略を確立した。
アザシチジンとHu5F9-G4とを用いた組み合わせ治療によるヒトマクロファージでの急性骨髄性白血病がん細胞の貪食除去の向上
AMLの治療についてアザシチジンとHu5F9-G4との組み合わせを評価した。アザシチジン(ビダーザ(登録商標))は、急性骨髄性白血病(AML)の治療に用いられている化学療法剤である。アザシチジンの抗がん作用は、脱メチル化、またはデオキシリボ核酸(DNA)のメチル化を妨害することに加え、急速に分裂するがん細胞が死滅する原因となる直接の細胞傷害効果をもたらすように細胞代謝を妨害することに起因すると考えられている。
hu5F9-G4用量漸増治療による高い病変負荷を有するマウスにおける急死の予防
この試験では、マウス異種移植モデルを用いて、ヒトAML疾患に対する用量漸増レジメンを、hu5F9-G4(ヒト化抗CD47抗体)により引き起こされる急死の予防戦略として研究した。これまでの研究で、本発明者らは、初期治療用量のhu5F9-G4がAML移植マウスの急死を引き起こすことを観察した。本発明者らはまた、高レベルの循環白血病細胞を有するマウスが急死したことから、急死が循環系病変の負荷に関係しているらしいということを確認した。本発明者らは、初期低用量のhu5F9-G4が循環系病変を排出し、その後、骨髄のクリアランスを実施するためのより多い治療用量の投与を容易とすることが可能となり得るという仮説を立てた。
AMLにおける薬物動態及び効果プロファイル
正常組織上におけるCD47の広範にわたる発現を考慮すると、治療hu5F9-G4用量は、白血病細胞を飽和及び除去するために、内部CD47シンクを飽和させることができるはずである。AML第1相試験において、hu5F9-G4投与レジメンが、内部CD47シンクを飽和させて、臨床的に実行可能な投与で有効な循環薬物レベルをもたらすことができるということが示されている。
AMLにおけるhu5F9-G4治療の治療効果
最大の10mg/kgのhu5F9-G4を週に2回投与された患者(コホート3)において、3名の患者のうちの2名(106及び702)は生物学的抗白血病活性を示した。これら2名の患者は、前臨床マウス異種移植モデルで観察されたhu5F9-G4抗白血病活性と同様の、著しい低形成骨髄及び確かな芽球数低下を示した。生物学的活性を有するこれらの患者において、いくつかの別の因子が注目に値する。第1に、これら2名の患者のうちの1名は、6ヶ月間を超えて継続中の長続きする効果を有し、>50%の芽球減少を伴う部分寛解(PR)を示した。臨床的にこの患者は、治療に対して十分に耐性を示しており、治療前におけるほぼ毎週から、3ヶ月目の間と治療後における1ヶ月間に1回へと、RBC輸血条件に大幅な改善が認められていた。
細胞減少剤とhu5F9-G4とを用いた組み合わせ治療
細胞減少治療薬とhu5F9-G4とを用いた共治療を行い循環白血病細胞負荷を軽減することにより、hu5F9-G4に関連する急死のリスクを軽減することができる。細胞減少治療薬とは、循環及び骨髄腫瘍負荷を軽減する因子のことであり、例えば、ヒドロキシウレア、経口エトポシド、ロイコフェレーシス、及びその他の細胞傷害性化学療法などの治療を含む。前臨床モデルでは、ヒドロキシウレアの効果、及び、継続中のhu5F9-G4治療に関する潜在的な追加毒性について、免疫応答性で野生型の健康なマウスを用いて評価を行った。
hu5F9-G4との腫瘍免疫療法薬の組み合わせ
モノクローナル遮断抗CD47抗体を用いて腫瘍細胞におけるCD47-SIRPαシグナル伝達軸を遮断すると、自然免疫機構と適応免疫機構の両方の活性化による腫瘍除去がもたらされる。自然免疫機構による抗CD47抗体介在性腫瘍除去は、マクロファージ及びその他の貪食細胞による腫瘍細胞の貪食除去を介して行われる。マクロファージが多くの腫瘍タイプに浸潤する一般的な免疫細胞であることが知られており、腫瘍内マクロファージ浸潤の度合いは臨床予後と相関している。マクロファージ浸潤と臨床疾患経過との相関関係は多くの場合、腫瘍進行を抑制する古典的活性化(M1)タイプのマクロファージ、または、腫瘍進行を促進する選択的活性化(M2)タイプのマクロファージのいずれかの存在に依存している。
バイオマーカー
hu5F9-G4に対する高い臨床効果を予測する白血病または前白血病状態(例えば、MDS)を有する患者を選択するための、分子、細胞遺伝学、免疫表現型、及び腫瘍微小環境のプロファイリングの使用。
hu5F9-G4 AML適応症
hu5F9-G4は、AMLの形態学的、分子的、及び細胞遺伝学なサブタイプにわたる広範な前臨床活性を有している。それゆえ、hu5F9-G4は、AMLにおける広範で潜在的な臨床活性を有し得る。特定の臨床適応症に関し、hu5F9-G4は、1)再発及び/または難治性の急性骨髄性白血病、2)標準的な低強度療法(例えば、脱メチル化因子による)に失敗し標準的な導入化学療法に不適格なAML患者、3)微小残存病変のエビデンスを有し形態学的な完全寛解を示すAML患者を治療することができる。
受容体占有率のアッセイ
本アッセイの概略を図7に示す。予定された時点(例えば、hu5F9-G4投与の1日前、hu5F9-G4投与の1日後など)に患者の末梢血及び骨髄吸引液を採取する。これらの試料を2つのチューブ、「RO試験」及び「RO飽和」に分配する。「RO飽和」は、100%受容体占有率(あらかじめ飽和を測定)をシミュレートするために200μg/mlのhu5F9-G4を用いてエクスビボで人工的に飽和させたものである。RO試験は、人工的に飽和させていないものである。その後、これらの2つのチューブを200μg/mlのAlexaFlour-647がコンジュゲートした抗IgG4(クローンG17-4)で染色して、赤血球及び白血球(芽球を含む)上の蛍光強度を測定する。それぞれの血液画分の受容体占有率を、RO飽和中央蛍光強度(MFI)で割ったRO試験MFIのパーセンテージ比として測定する。
例示的な臨床投与プロトコルを図8に示す。上の表は第1相臨床試験に用いるより少ない用量範囲を示し、下の表は臨床的に意義がある投与スケジュールを示す。
本出願は、2017年 6月21日出願の米国仮特許出願番号62/523,182の利益を主張するものであり、その出願全体は本明細書に参照として組み込まれる。
Claims (13)
- 患者において血液悪性腫瘍を治療する方法における、前記血液悪性腫瘍を治療するための組成物であって、前記組成物は、CD47に特異的に結合してCD47のSIRPαへの結合を抑制する抗CD47抗体を含み、前記組成物は、脱メチル化因子と組み合わせて投与されることを特徴とし、前記脱メチル化因子はアザシチジンである、
組成物。 - 前記血液悪性腫瘍は、
(a)白血病、
(b)急性骨髄性白血病(AML)、または
(c)骨髄異形成症候群(MDS)
である、請求項1に記載の組成物。 - 前記抗CD47抗体は、Hu5F9-G4である、請求項1または2に記載の組成物。
- 請求項1に記載の組成物であって、
前記方法は、
前記患者に由来する骨髄芽球において約80%超のCD47受容体占有率が達成される治療用量に到達する漸増用量レジメンで前記組成物を投与することと、
前記血液悪性腫瘍を治療するために十分な期間にわたり前記治療用量を投与することと
を含む、
組成物。 - 前記血液悪性腫瘍は、
(a)白血病、
(b)急性骨髄性白血病(AML)、または
(c)骨髄異形成症候群(MDS)
である、請求項4に記載の組成物。 - 前記方法は、追加の治療因子の投与を更に含んでおり、
前記追加の治療因子は、任意選択的に、Bcl-2阻害剤、任意選択的に、オバトクラックス、ベンクレクスタ、もしくはゴシポールであるBcl-2阻害剤である、請求項4または請求項5に記載の組成物。 - 前記方法は、血液悪性腫瘍を患う患者が治療のための循環腫瘍細胞の安全レベルを有していることを確認する過程を更に含んでおり、任意選択的に、前記循環腫瘍細胞の安全レベルは約10×109循環芽球/リットル未満である、請求項4から6のいずれか一項に記載の組成物。
- 前記方法は、患者が循環腫瘍細胞の安全レベルを有していないことを確認する過程を更に含んでおり、循環腫瘍細胞の安全レベルを達成するために、初期の治療用量以下の前記組成物を投与することにより、または、細胞減少療法を実施することにより、患者は治療され、任意選択的に、前記細胞減少療法はヒドロキシウレアの投与を含む、請求項4から6のいずれか一項に記載の組成物。
- 前記方法は、
(a)漸増用量レジメンで前記組成物を投与する前に、前記患者の循環芽球または白血球を測定する過程、及び/または
(b)骨髄におけるCD47受容体占有率を測定する過程
を更に含む、請求項4から8のいずれか一項に記載の組成物。 - 前記抗CD47抗体の初期用量は約1mg/kg/投与である、請求項4から9のいずれか一項に記載の組成物。
- 用量は約1~30mg/kg/投与分漸増される、請求項10に記載の組成物。
- 用量は週に2回から隔週で漸増される、請求項11に記載の組成物。
- 前記組成物は週に2回から隔週で投与される、請求項11または請求項12に記載の組成物。
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WO2015041987A1 (en) | 2013-09-18 | 2015-03-26 | The Board Of Trustees Of The Leland Stanford Junior University | Modulation of efferocytosis pathways for treatment of atherosclerotic disease |
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JP2018535692A (ja) * | 2015-09-21 | 2018-12-06 | エラスムス ユニバーシティ メディカル センターErasmus University Medical Center | 抗cd47抗体及び使用方法 |
WO2018237168A1 (en) * | 2017-06-21 | 2018-12-27 | The Board Of Trustees Of The Leland Stanford Junior University | DOSING PARAMETERS FOR CD47 TARGETING THERAPIES WITH HEMATOLOGICAL MALIGNANCIES |
-
2018
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Non-Patent Citations (2)
Title |
---|
mAbs, 2010, Vol. 2, Issue 4, pp. 440-448 |
PLoS ONE, 2015, 10(9), e0137345, pp. 1-23 |
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