JP2016502083A - 長時間作用型トポイソメラーゼi阻害薬による乳癌治療の有効性を評価及び予測する方法 - Google Patents
長時間作用型トポイソメラーゼi阻害薬による乳癌治療の有効性を評価及び予測する方法 Download PDFInfo
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Abstract
Description
本願は、米国特許法第119条(e)に基づき、2012年11月28日に出願された米国仮特許出願第61/730,900号明細書に対する優先権の利益を主張するものであり、この仮特許出願の開示は全体として参照により本明細書に援用される。
最初に同定されたトポイソメラーゼI阻害薬(inhbitor)はカンプトテシンであった。カンプトテシン(多くの場合に「CPT」と略される)は、当初カンレンボク(Camptotheca acuminata)(ヌマミズキ科(Nyssaceae))の木及び樹皮から単離された植物毒アルカロイドである。この化合物は、20S配置のラクトンE環に不斉中心を持つ五環系を有する。この五環系は、ピロロ[3,4−b]キノリン(A環、B環及びC環)、共役ピリドン(D環)、及び20位水酸基を有する六員ラクトン(E環)を含む。カンプトテシンは水に不溶性であるため、最初は、ラクトン環を開環させてナトリウム塩を形成して水溶性カルボン酸塩の形態で臨床的に評価された。カンプトテシン及びその誘導体の多くに付随する低い水溶解度に対処しようと、いくつかの合成の試みは、A環及び/又はB環を誘導体化するか又は20−ヒドロキシルをエステル化することにより、細胞傷害活性を維持しながらも水溶解度を改善することに向けられてきた。例えば、トポテカン(9−ジメチルアミノメチル−10−ヒドロキシCPT)、10−ヒドロキシ−7−エチル−カンプトテシン(SN−38としても知られる、イリノテカンの加水分解により生じる代謝産物)及び別名CPT−11として知られるイリノテカン(7−エチル−10[4−(1−ピペリジノ)−1−ピペリジノ]カルボニルオキシCPTは、臨床的に有用な活性を示している水溶性CPT誘導体である。最近になって、前述したようなトポイソメラーゼI阻害薬の長時間作用形態が開発されている。例えば、米国特許第8,263,062号明細書及び同第7,744,861号明細書、Zhao,H.,et al.,Bioconjugate Chem.2008,19,849−859、及びSapra,P.,et al.,Haematologica,2009;94(10),1456−1459を参照のこと。かかる長時間作用型トポイソメラーゼI阻害薬は、乳癌を含む様々なヒト異種移植片腫瘍に対して有効であることが示されている(Persson,H.,et al.,AACR−NCI−EORTC Intl Conference on Molecular Targets and Cancer Therapeutics,Oct.22−26,2007,S.F.CA.Poster No.C10)。
初期全身療法(primary systemic therapy)を受けた後に手術を行う乳癌診断患者が増え続けている。乳癌などのある種の癌では、治療に対する患者の反応をモニタすることが、その反応の程度によって無病生存及び全生存に関する重要な予後判定情報が提供され得るため、治療の不可欠な要素である。組織病理学は、残存腫瘍の規模及び腫瘍組織内の退行性病変に基づき治療有効性の正確な評価を提供する。しかしながら病理学的完全奏効を得る乳癌患者は僅か20%に過ぎず、治療の初期に治療有効性をモニタする方法を必要とすることは事実である(Avril,N.et al.,The Journal of Nuclear Medicine,50(5)Suppl.,May 2009,55S−63S)。効果のない治療を早期に特定することは、転移性乳癌患者においても、緩和治療の選択肢の数に起因して有用であり得る。治療初期における有効性の評価に一般に用いられる方法としては、MRI(磁気共鳴画像法)(これは高価で、且つ極めて特殊な機器及び高度な訓練を受けた専門家の両方が必要である)、及びCT(コンピュータ体軸断層撮影)走査などの放射線に基づく方法が挙げられる。乳癌治療中に治療有効性を予測するための新規の改良された方法、特に効率的で簡便な、且つ費用対効果の高い方法があれば、治療を個別化及びオーダーメイド化し、且つ効果のない化学療法を回避する助けとなり得る。
本明細書で使用されるとき、単数形「a」、「an」、及び「the」には、文脈上特に明確に指示されない限り複数の指示対象が含まれる。
上記に指摘したとおり、本発明は、(特に)乳癌などの癌に罹患している者の治療であって、その罹患者に長時間作用型トポイソメラーゼI阻害薬を投与し、且つ罹患者における1つ以上の腫瘍マーカーのレベルを長時間作用型トポイソメラーゼI阻害薬による治療に対する癌の反応と相関付けることによる、それによって治療の治療効果を予測及び評価する方法を提供する治療に関する。
本明細書に記載される方法は、長時間作用型トポイソメラーゼI阻害薬の投与を含む。これに関して、本発明は、トポイソメラーゼI阻害薬が長時間作用型である限り、いかなる特定のトポイソメラーゼI阻害薬にも限定されるものではない。トポイソメラーゼ阻害薬の実効半減期が以下の範囲の1つ以上を満たすとき、トポイソメラーゼI阻害薬は長時間作用型である:約5日〜約60日;約9日〜約60日;約13日〜約60日;約21日〜約60日;約28日〜約60日;約35日〜約60日;約42日〜約60;及び約49日〜約60日。本方法で使用される例示的長時間作用型トポイソメラーゼ−I阻害化合物としては、長時間作用形態のカンプトテシン、カンプトテシン誘導体及び代謝産物、例えばカンプトテシン、トポテカン、イリノテカン、SN−38、10−ヒドロキシカンプトテシン、及び11−ヒドロキシカンプトテシンが挙げられる。
C−[CH2−O−(CH2CH2O)n−CH2−Term]4、
[式中、nは、それぞれの場合に、5〜150の値(例えば約113)を有する整数であり;及びTermは、それぞれの場合に、−OH、−C(O)OH、
[式中、各nは、40〜約500の範囲の整数(例えば、約113及び約226)である]、及びその薬学的に許容可能な塩(混合塩を含む)である。上記及び他の化合物が米国特許第7,744,861号明細書に記載されており、「イリノテカンのペンタエリスリトール系マルチアームポリマーコンジュゲート(pentaerythritol−based multi−arm polymer conjugates of irinotecan)」、即ち「PBMAPCI」と見なされる。
以前治療された転移性乳癌を有する患者におけるペンタエリスリトリル−4−アーム−(PEG−1−メチレン−2オキソ−ビニルアミノアセテート結合イリノテカン)−20Kの2つの異なる投薬スケジュールの有効性及び安全性評価
この試験には70人の患者が登録した(各治療群n=35)。患者の年齢中央値は54.5歳(範囲33〜83歳)であり、ECOGパフォーマンスステータスは40%が0及び60%が1であり、初期診断から化学療法薬投与までの時間の中央値は4.5年(範囲0〜19年)であり、及びMBC(転移性乳癌)に対する細胞傷害レジメン数の中央値は2であった。全ての患者が以前にタキサンによる治療を受けたことがあった(76%ドセタキセル;40%パクリタキセル);89%が先行するアントラサイクリン(63%エピルビシン;24%ドキソルビシン及び1人の患者はミトキサントロンによる)を受けたことがあった;及び27%の患者がカペシタビンを受けたことがあった。15人(21.4%)の患者が先行するベバシズマブを受けたことがあった。5人のHER2陽性疾患患者の中では、全患者が先行するトラスツズマブを受けたことがあり;先行するラパチニブを受けたことがある者はいなかった。
スクリーニングにおけるCA27.29バイオマーカー測定
実施例1に記載する試験に基づき分析データセットを作成した。利用可能なスクリーニング値を有する48人の患者からのベースラインCA27.29測定値を表2に示す。
CA27.29の動態をSN−38曝露、腫瘍サイズ、及びRECISTと関係付ける数学的モデルの開発
各患者の血漿SN−38濃度−時間プロファイルを予測するモデルを、投与情報及び以前開発された母集団PKモデル(M.A.Eldon,U.Hoch.,J.Clin Oncol,29:2011(suppl;abstr 2598))に基づき考案した。このモデルの目的は、予測された血漿SN−38濃度と血清CA27.29濃度との関係を調べること、及びSN−38がCA27.29の産生を(間接的に)阻害するかどうかを試験することであった。
Claims (23)
- 乳癌を有する対象におけるSN−38及びイリノテカンから選択される長時間作用型トポイソメラーゼ−I阻害薬による治療に対する反応を評価する方法であって、
(i)前記対象の体液試料中の腫瘍マーカーのレベルを決定して前記腫瘍マーカーの基準レベルを提供するステップであって、前記腫瘍マーカーが、CA27.29、CA15−3及びCEAから選択される、ステップと、
(ii)ある投薬量の前記長時間作用型トポイソメラーゼ−I阻害薬を所与の投薬スケジュールで投与することにより、前記対象を少なくとも2週間の期間にわたり治療するステップと、
(iii)前記ステップ(ii)における前記治療の後に前記対象の体液試料中の前記腫瘍マーカーのレベルを決定するステップであって、前記体液がステップ(i)と同じである、ステップと、
(iv)ステップ(iii)における前記腫瘍マーカーの前記レベルを前記長時間作用型トポイソメラーゼ−I阻害薬による治療に対する前記乳癌の反応と相関付けるステップであって、ステップ(iii)における前記腫瘍マーカーのレベルがステップ(i)における前記基準レベルと変わらないか又はそれより低下している場合、正の治療反応と判定され、及びステップ(iii)における腫瘍マーカーのレベルがステップ(i)における前記基準レベルより増加している場合、負の治療反応と判定される、ステップと
を含む方法。 - 前記治療ステップにより生じるSN−38に対する前記乳癌の曝露が、前記対象における前記腫瘍マーカーのレベル及び前記治療レジメンの有効性と相関する、請求項1に記載の方法。
- 前記長時間作用型トポイソメラーゼ−I阻害薬が、1つ以上の水溶性ポリマーとの遊離可能な共有結合により修飾されているSN−38を含む、請求項1に記載の方法。
- 前記長時間作用型トポイソメラーゼ−I阻害薬が、1つ以上の水溶性ポリマーとの遊離可能な共有結合により修飾されているイリノテカンを含む、請求項1に記載の方法。
- 前記1つ以上の水溶性ポリマーがポリエチレングリコールを含む、請求項3又は4に記載の方法。
- 前記長時間作用型トポイソメラーゼ−I阻害薬が、ペンタエリスリトリル−4−アーム−(ポリエチレングリコール−1−メチレン−2オキソ−ビニルアミノアセテート結合イリノテカン)である、請求項5に記載の方法。
- ステップ(i)において、前記長時間作用型トポイソメラーゼ−I阻害薬による治療の前に前記腫瘍マーカーのレベルが決定される、請求項1〜7のいずれか一項に記載の方法。
- ステップ(i)及び(iii)における前記体液試料が、血漿、血清、及び血液から選択される、請求項1〜7のいずれか一項に記載の方法。
- ステップ(i)における前記腫瘍マーカーの前記基準レベルが正常ベースラインレベルと比べて高い、請求項1〜7のいずれか一項に記載の方法。
- 前記腫瘍マーカーがCA27.29であり、CA27.29の前記基準レベルが38U/ml超である、請求項10に記載の方法。
- 前記腫瘍マーカーがCA15−3であり、CA15−3の前記基準レベルが30U/ml超である、請求項10に記載の方法。
- 前記治療期間が少なくとも3週間である、請求項1〜12のいずれか一項に記載の方法。
- 前記治療期間が少なくとも6週間である、請求項13に記載の方法。
- 前記治療期間が少なくとも12週間である、請求項14に記載の方法。
- 前記腫瘍マーカーのレベルがイムノアッセイにより決定される、請求項1〜15のいずれか一項に記載の方法。
- 第6週までの少なくとも25%の前記腫瘍マーカーのレベルの低下が、少なくとも4ヶ月の前記対象における無進行生存と正の相関を示す、請求項1〜16のいずれか一項に記載の方法。
- 前記長時間作用型トポイソメラーゼ阻害薬Iによる追加的な治療後か又は治療中止後のいずれかに、ステップ(iii)が任意選択で繰り返される、請求項1〜16のいずれか一項に記載の方法。
- ステップ(iv)において負の治療反応を判定する場合、ステップ(ii)における前記投薬量又は投薬スケジュールの一方又は両方が変更される、請求項1〜16のいずれか一項に記載の方法。
- 乳癌と診断された対象における長時間作用型トポイソメラーゼ−I阻害薬による治療の有効性を予測するための、血液、血清、及び血漿から選択される体液中におけるCA27.29、CA15−3及びCEAから選択される腫瘍マーカーのレベルの使用であって、前記長時間作用型トポイソメラーゼ−I阻害薬が長時間作用型イリノテカン及び長時間作用型SN−38から選択される、使用。
- 乳癌と診断された対象における長時間作用型トポイソメラーゼ−I阻害薬による前記乳癌の治療によりもたらされる諸レベルのSN−38に対する前記乳癌の曝露を予測するための、血液、血清、及び血漿から選択される体液中におけるCA27.29、CA15−3及びCEAから選択される腫瘍マーカーのレベルの使用であって、前記長時間作用型トポイソメラーゼ−I阻害薬が長時間作用型イリノテカン及び長時間作用型SN−38から選択され、及びSN−38に対する前記乳癌の曝露が治療の有効性と相関する、使用。
- 前記対象が転移性乳癌を有する、請求項1〜19のいずれか一項に記載の方法又は請求項20又は21に記載の使用。
- 前記方法又は使用以前、前記対象は前記乳癌に対するタキサン系治療が不奏効であった、請求項1〜19のいずれか一項に記載の方法又は請求項20又は21に記載の使用。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007505928A (ja) * | 2003-09-17 | 2007-03-15 | ネクター セラピューティクス アラバマ,コーポレイション | 多分岐ポリマーのプロドラッグ |
JP2007526455A (ja) * | 2004-02-03 | 2007-09-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 癌を特徴付ける、制御する、診断する、および処置するための組成物ならびに方法 |
JP2009506076A (ja) * | 2005-08-26 | 2009-02-12 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・レランド・スタンフォード・ジュニア・ユニバーシティ | 三叉神経疼痛のための薬物送達のための治療手順 |
WO2009059393A1 (en) * | 2007-11-06 | 2009-05-14 | University Health Network | Method for the detection of breast cancer by determining alcam and/or bcam levels in a patient sample |
WO2010036335A1 (en) * | 2008-09-23 | 2010-04-01 | Nektar Therapeutics | Compositions and methods for achieving sustained therapeutic drug concentrations in a subject |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9704444D0 (en) * | 1997-03-04 | 1997-04-23 | Isis Innovation | Non-invasive prenatal diagnosis |
US6355623B2 (en) * | 1998-09-24 | 2002-03-12 | Hopital-Sainte-Justine | Method of treating IBD/Crohn's disease and related conditions wherein drug metabolite levels in host blood cells determine subsequent dosage |
US20020103141A1 (en) * | 1998-12-23 | 2002-08-01 | Mckearn John P. | Antiangiogenic combination therapy for the treatment of cancer |
US8394365B2 (en) | 2003-09-17 | 2013-03-12 | Nektar Therapeutics | Multi-arm polymer prodrugs |
JP5265384B2 (ja) * | 2006-02-09 | 2013-08-14 | エンゾン ファーマスーティカルズ インコーポレイテッド | 乳癌、結腸直腸癌、膵臓癌、卵巣癌及び肺癌の治療のための7−エチル−10−ヒドロキシカンプトセシンのマルチアーム・ポリマー複合体 |
AU2010321882B2 (en) | 2009-11-18 | 2016-01-14 | Nektar Therapeutics | Salt form of a multi-arm polymer-drug conjugate |
KR20130043104A (ko) | 2010-04-06 | 2013-04-29 | 카리스 라이프 사이언스 룩셈부르크 홀딩스 | 질병용 순환 생물학적 지표들 |
WO2012031320A1 (en) * | 2010-09-06 | 2012-03-15 | Peter Maccallum Cancer Institute | Cancer diagnostic |
JP6138140B2 (ja) | 2011-10-25 | 2017-05-31 | ネクター セラピューティクス | 癌患者の治療 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007505928A (ja) * | 2003-09-17 | 2007-03-15 | ネクター セラピューティクス アラバマ,コーポレイション | 多分岐ポリマーのプロドラッグ |
JP2007526455A (ja) * | 2004-02-03 | 2007-09-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 癌を特徴付ける、制御する、診断する、および処置するための組成物ならびに方法 |
JP2009506076A (ja) * | 2005-08-26 | 2009-02-12 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・レランド・スタンフォード・ジュニア・ユニバーシティ | 三叉神経疼痛のための薬物送達のための治療手順 |
WO2009059393A1 (en) * | 2007-11-06 | 2009-05-14 | University Health Network | Method for the detection of breast cancer by determining alcam and/or bcam levels in a patient sample |
WO2010036335A1 (en) * | 2008-09-23 | 2010-04-01 | Nektar Therapeutics | Compositions and methods for achieving sustained therapeutic drug concentrations in a subject |
Non-Patent Citations (3)
Title |
---|
EUR J CANCER, vol. 37, JPN6017022723, 2001, pages 355 - 363, ISSN: 0003584005 * |
J CLIN ONCOL, vol. 25, no. 33, JPN6017022725, 2007, pages 5287 - 5312, ISSN: 0003584006 * |
TUMOR BIOL, vol. 26, JPN6017022720, 2005, pages 281 - 293, ISSN: 0003584007 * |
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