JP2021130668A - 多発性骨髄腫(mm)の処置 - Google Patents
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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Abstract
Description
本出願は、ASCII形式で電子的に提出された配列表を含有し、参照によってその全体が本明細書に組み込まれる。前記ASCIIのコピーは、2016年5月4日に作成され、MS231 PCT_SL.txtと名付けられ、8,236バイトのサイズである。
態様は、多発性骨髄腫の処置が必要な対象において多発性骨髄腫を処置する方法であって、対象に、CD38に特異的な抗体の治療的に有効な量を投与することを含み、前記抗体は、配列GFTFSSYYMN(配列番号1)またはSYYMN(配列番号2)のHCDR1領域、配列GISGDPSNTYYADSVKG(配列番号3)のHCDR2領域、配列DLPLVYTGFAY(配列番号4)のHCDR3、配列SGDNLRHYYVY(配列番号5)のLCDR1領域、配列GDSKRPS(配列番号6)のLCDR2領域、および配列QTYTGGASL(配列番号7)のLCDR3領域を含み、前記抗体は、8mg/kg以上の用量にて投与される。
研究は、ヒト抗CD38抗体MOR03087(MOR202)の安全性および予備的な有効性を特徴付けるための、再発性/難治性多発性骨髄腫を患う成人対象における、単剤療法としての、そして再発性/難治性多発性骨髄腫を患う成人対象における、標準的な治療と組み合わせての、非盲検の、マルチセンターでの、服用漸増(3+3設計)研究であった。ClinicalTrials.gov Identifier:NCT01421 186。
1.>18歳であった、
2.以下として定義される再発性または難治性の多発性骨髄腫:
(i)免疫調節剤およびプロテアソーム阻害剤を(一緒に、または異なる療法の一部として)含んだ少なくとも2回の前治療の失敗、(ii)全ての対象は、多発性骨髄腫の最後の前治療の間またはその後に、進行を実証した
(i)レナリドマイドおよびプロテアソーム阻害剤を含む少なくとも2回の前治療、(ii)全ての対象は、多発性骨髄腫の最後の前治療後の60日の間に、またはその60日以内に、進行を実証した
(i)少なくとも1回の前治療を受けた、(ii)全ての対象は、多発性骨髄腫の最後の前治療の間またはその後に、進行を実証した
1.100mLあたり≧0.5g(≧5g/L)の血清Mタンパク質、および/または24時間あたり≧200mgの尿Mタンパク質の存在
2.絶対的好中球数(ANC)≧1,000/mm3
3.ヘモグロビン≧8g/dL、そして
4.全ての研究に関連した手順、医薬品の使用、および評価を遵守する能力。
第1の研究結果の測定値は、以下の通りであった:
1.デキサメタゾン(DEX)あり、そしてなしの単剤療法としての、そしてポマリドミド(POM)/DEXおよびレナリドマイド(LEN)/DEXと組み合わせた、MOR202の最大耐容用量(MTD)および/または推奨される用量/スケジュールを同定。
2.有害事象(AE)の発生率および重篤度によって安全性を評価。
3.MOR202の免疫原性を評価。
1.POM/DEXおよびLEN/DEXなし、そしてありのMOR202の薬物動態(PK)を評価。
2.全奏効率、奏効期間、進行までの時間、および無増悪生存期間を同定。
免疫調節薬物およびプロテアソーム阻害剤を含む2回の前治療が失敗したrrMM患者において、パートA〜パートCを行った。
パートA(コホート1〜6)の患者を、最大で2サイクルについてだけ(2×28日)処置した。その後のコホートの患者を、疾患進行(PD)まで、最大2年間、処置した/することにする。
42人(100%)の患者が、原因に拘りなく、処置中に有害事象(AE)を経験した。
2時間のIV注入が、全ての患者において実行可能であった。注入関連反応(IRR)が、DEXなしのMOR202を受けた13人(31%)の患者において、主に第1の注入中に起こった。
図2は、2015年4月13日現在の奏効を示す。図3は、現在までのMタンパク質の変化を示す。
図7A〜図7Dは、MOR202血清濃度を経時的に示している。4mg/kgをq2wで処置した殆どの患者において、ドミナント標的媒介性シンク作用(dominant target−mediated sink effect)が観察されて、低い、または少しも検出可能でない血清トラフレベルの原因となった。図7Aおよび図7C参照。対照的に、≧4mg/kgをq1wで処置した患者は、一定した、または僅かに増大したトラフレベルを示した。図7Bおよび図7D参照。
Claims (10)
- CD38に特異的な抗体において、多発性骨髄腫の処置に用いられる配列GFTFSSYYMN(配列番号1)またはSYYMN(配列番号2)のHCDR1領域、配列GISGDPSNTYYADSVKG(配列番号3)のHCDR2領域、配列DLPLVYTGFAY(配列番号4)のHCDR3、配列SGDNLRHYYVY(配列番号5)のLCDR1領域、配列GDSKRPS(配列番号6)のLCDR2領域、および配列QTYTGGASL(配列番号7)のLCDR3領域を含み、8mg/kg以上の用量にて投与されることを特徴とする抗体。
- 請求項1に記載の抗体において、16mg/kg以上の用量にて投与されることを特徴とする抗体。
- 請求項1または2に記載の抗体において、少なくとも8週にわたって、2週毎に1回(q2w)投与されることを特徴とする抗体。
- 請求項1乃至3の何れか1項に記載の抗体において、少なくとも8週にわたって、週1回(q1w)投与されることを特徴とする抗体。
- 請求項1乃至4の何れか1項に記載の抗体において、静脈内に投与されることを特徴とする抗体。
- 請求項1乃至5の何れか1項に記載の抗体において、2時間にわたって、静脈内に投与されることを特徴とする抗体。
- 請求項1乃至7の何れか1項に記載の抗体において、IgG1 Fc領域を含むことを特徴とする抗体。
- 請求項1乃至8の何れか1項に記載の抗体において、デキサメタゾンと組み合わせて投与されることを特徴とする抗体。
- 請求項9に記載の抗体において、デキサメタゾンと組み合わせて投与され、デキサメタゾンは、週1回(q1W)、20mgまたは40mgにて投薬されることを特徴とする、抗体。
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US10533057B2 (en) | 2020-01-14 |
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