JP2021531306A - 神経内分泌腫瘍の処置の方法 - Google Patents
神経内分泌腫瘍の処置の方法 Download PDFInfo
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Abstract
Description
本願は、ASCII形式で電子的に提出された配列表(ファイル名PAT058249_SL.txt)を含み、この配列表は、全体として参照により本明細書に援用される。
(a)錯体であって、
(ai)放射性核種177Lu(ルテチウム−177)であって、それが250〜500MBq/mLの容積測定による放射能を提供する濃度における放射性核種177Lu(ルテチウム−177)、及び
(aii)DOTAが連結されたソマトスタチン受容体結合ペプチド[DOTA0,D−Phe1,Tyr3]オクトレオテート
によって形成される錯体;
(b)放射線分解に対する安定剤、(bi)0.5〜1mg/mLの濃度のゲンチシン酸、及び(bii)2.0〜5.0mg/mLの濃度のアスコルビン酸;
(c)0.01〜0.10mg/mLの濃度のジエチレントリアミン五酢酸(DTPA)又はその塩;及び
(d)酢酸緩衝液であって、
(di)0.3〜0.7mg/mLの濃度の酢酸;及び
(dii)0.4〜0.9mg/mLの濃度の酢酸ナトリウム
で構成され、好ましくは、4.5〜6.0のpH、好ましくは5.0〜5.5のpHを提供する酢酸緩衝液
を含む医薬水溶液として製剤化され得る。
(a)錯体であって、
(ai)放射性核種177Lu(ルテチウム−177)であって、それが250〜500MBq/mLの容積測定による放射能を提供する濃度における放射性核種177Lu(ルテチウム−177)、及び
(aii)DOTAが連結されたソマトスタチン受容体結合ペプチド、例えばオキソドトレオチド又はエドトレオチド
によって形成される錯体;
(b)放射線分解に対する安定剤、(bi)0.5〜1mg/mLの濃度のゲンチシン酸、及び(bii)2.0〜5.0mg/mLの濃度のアスコルビン酸;
(c)0.01〜0.10mg/mLの濃度のジエチレントリアミン五酢酸(DTPA)又はその塩;及び
(d)酢酸緩衝液であって、
(di)0.3〜0.7mg/mLの濃度の酢酸;及び
(dii)0.4〜0.9mg/mLの濃度の酢酸ナトリウム
で構成され、好ましくは、4.5〜6.0のpH、好ましくは5.0〜5.5のpHを提供する酢酸緩衝液
を含む医薬水溶液として製剤化される、実施形態3〜7のいずれか1つの使用のための組み合わせ又は方法。
本明細書で使用されるとき、冠詞「1つの(a)」及び「1つの(an)」は、その冠詞の文法上の指示対象の1つ又は2つ以上(例えば、少なくとも1つ)を指す。
一実施形態において、本明細書に記載される組み合わせは、抗体分子である治療剤を含む。
ある実施形態において、抗体分子は、多重特異性抗体分子であり、例えば、それは、複数の免疫グロブリン可変ドメイン配列を含み、その複数のうちの第1の免疫グロブリン可変ドメイン配列は、第1のエピトープに対する結合特異性を有し、その複数のうちの第2の免疫グロブリン可変ドメイン配列は、第2のエピトープに対する結合特異性を有する。ある実施形態において、第1及び第2のエピトープは、同じ抗原、例えば同じタンパク質(又は多量体タンパク質のサブユニット)上にある。ある実施形態において、第1及び第2のエピトープは、重複する。ある実施形態において、第1及び第2のエピトープは、重複しない。ある実施形態において、第1及び第2のエピトープは、異なる抗原、例えば異なるタンパク質(又は多量体タンパク質の異なるサブユニット)上にある。ある実施形態において、多重特異性抗体分子は、第3、第4又は第5の免疫グロブリン可変ドメインを含む。ある実施形態において、多重特異性抗体分子は、二重特異性抗体分子、三重特異性抗体分子又は四重特異性抗体分子である。
選択されたPD−1阻害剤
プログラム死1(PD−1)タンパク質は、T細胞制御因子の拡張CD28/CTLA−4ファミリーの阻害性メンバーである(Okazaki et al.(2002)Curr Opin Immunol 14:391779−82;Bennett et al.(2003)J.Immunol.170:711−8)。PD−1のための2つのリガンド、PD−L1(B7−H1)及びPD−L2(B7−DC)が同定されており、これは、PD−1への結合時にT細胞活性化を下方制御することが示されている(Freeman et al.(2000)J.Exp.Med.192:1027−34;Carter et al.(2002)Eur.J.Immunol.32:634−43)。PD−L1は、様々なヒト癌において富んでいる(Dong et al.(2002)Nat.Med.8:787−9)。
一実施形態において、PD−1阻害剤は、抗PD−1抗体分子である。一実施形態において、PD−1阻害剤は、全体として参照により援用される「Antibody Molecules to PD−1 and Uses Thereof」という名称の2015年7月30日に公開された米国特許出願公開第2015/0210769号明細書において記載される抗PD−1抗体分子である。一部の実施形態において、抗PD−1抗体分子は、スパルタリズマブ(PDR001)である。
一実施形態において、抗PD−1抗体分子は、ランブロリズマブ、MK−3475、MK03475、SCH−900475又はKEYTRUDA(登録商標)としても知られるペムブロリズマブ(Merck&Co)である。ペムブロリズマブ及び他の抗PD−1抗体は、全体として参照により援用されるHamid,O.et al.(2013)New England Journal of Medicine 369(2):134−44、米国特許第8,354,509号明細書及び国際公開第2009/114335号パンフレットに開示される。一実施形態において、抗PD−1抗体分子は、例えば、表2に開示されるとおりのペムブロリズマブのCDR配列の1つ以上(又は一括して全てのCDR配列)、重鎖若しくは軽鎖可変領域配列又は重鎖若しくは軽鎖配列を含む。
ある実施形態において、組み合わせは、PD−1阻害剤(例えば、PDR001)及びmTOR阻害剤、例えばRAD001(エベロリムスとしても知られる)を含む。一部の実施形態において、組み合わせは、PDR001及びmTOR阻害剤、例えばRAD001を含む。一部の実施形態において、組み合わせは、PDR001及びRAD001を含む。一部の実施形態において、mTOR阻害剤、例えばRAD001は、少なくとも0.5mg、1mg、2mg、3mg、4mg、5mg、6mg、7mg、8mg、9mg又は10mgの用量で週1回投与される。一部の実施形態において、mTOR阻害剤、例えばRAD001は、10mgの用量で週1回投与される。一部の実施形態において、mTOR阻害剤、例えばRAD001は、5mgの用量で週1回投与される。一部の実施形態において、mTOR阻害剤、例えばRAD001は、少なくとも0.5mg、1mg、2mg、3mg、4mg、5mg、6mg、7mg、8mg、9mg又は10mgの用量で1日1回投与される。一部の実施形態において、mTOR阻害剤、例えばRAD001は、0.5mgの用量で1日1回投与される。一部の実施形態において、組み合わせは、例えば、癌、例えば本明細書に記載される癌、例えば結腸直腸癌を処置するための治療有効量で対象に投与される。
特定の実施形態において、本明細書に記載される組み合わせは、LAG−3阻害剤を含む。一部の実施形態において、LAG−3阻害剤は、LAG525(Novartis)、BMS−986016(Bristol−Myers Squibb)又はTSR−033(Tesaro)から選択される。
一実施形態において、LAG−3阻害剤は、抗LAG−3抗体分子である。一実施形態において、LAG−3阻害剤は、全体として参照により援用される「Antibody Molecules to LAG−3 and Uses Thereof」という名称の2015年9月17日に公開された米国特許出願公開第2015/0259420号明細書において開示されるとおりの抗LAG−3抗体分子である。
一実施形態において、抗LAG−3抗体分子は、BMS986016としても知られるBMS−986016(Bristol−Myers Squibb)である。BMS−986016及び他の抗LAG−3抗体は、全体として参照により援用される国際公開第2015/116539号パンフレット及び米国特許第9,505,839号明細書に開示される。一実施形態において、抗LAG−3抗体分子は、例えば、表6に開示されるとおりのBMS−986016のCDR配列の1つ以上(又は一括して全てのCDR配列)、重鎖若しくは軽鎖可変領域配列又は重鎖若しくは軽鎖配列を含む。
特定の実施形態において、本明細書に記載される組み合わせは、TIM−3阻害剤を含む。理論に束縛されるものではないが、TIM−3はThe Cancer Genome Atlas(TCGA)データベースにおける腫瘍骨髄シグネチャーと相関し、正常末梢血単核球(PBMC)上で最も豊富なTIM−3は骨髄細胞上に存在すると考えられる。TIM−3は、単球、マクロファージ及び樹状細胞を含むが、これらに限定されないヒトPBMCにおける複数の骨髄サブセット上で発現される。
一実施形態において、TIM−3阻害剤は、抗TIM−3抗体分子である。一実施形態において、TIM−3阻害剤は、全体として参照により援用される「Antibody Molecules to TIM−3 and Uses Thereof」という名称の2015年8月6日に公開された米国特許出願公開第2015/0218274号明細書において開示される抗TIM−3抗体分子である。
一実施形態において、抗TIM−3抗体分子は、TSR−022(AnaptysBio/Tesaro)である。一実施形態において、抗TIM−3抗体分子は、TSR−022のCDR配列の1つ以上(又は一括して全てのCDR配列)、重鎖若しくは軽鎖可変領域配列又は重鎖若しくは軽鎖配列を含む。一実施形態において、抗TIM−3抗体分子は、例えば、表8に開示されるとおりのAPE5137又はAPE5121のCDR配列の1つ以上(又は一括して全てのCDR配列)、重鎖若しくは軽鎖可変領域配列又は重鎖若しくは軽鎖配列を含む。APE5137、APE5121及び他の抗TIM−3抗体は、全体として参照により援用される国際公開第2016/161270号パンフレットに開示される。
グルココルチコイド誘導性TNFR関連タンパク質(GITR)は、腫瘍壊死因子スーパーファミリー(TNFRSF)のメンバーである。GITR発現は、活性化時に更に増加され得るマウス及びヒトCD4+CD25+制御性T細胞において恒常的に検出される。対照的に、エフェクターCD4+CD25−T細胞及びCD8+CD25−T細胞は、低〜検出不可能なレベルのGITRTを発現し、T細胞受容体活性化後に迅速に上方制御される。GITRの発現は、活性化NK細胞、樹状細胞及びマクロファージ上でも検出されている。GITRのシグナル伝達経路の下流は、MAPK及び古典的なNFκB経路を含むことが示されている。様々なTRAFファミリーメンバーは、GITRのシグナル伝達中間体の下流として関係付けられてきた(Nocentini et al.(2005)Eur.J.Immunol.35:1016−1022)。
一実施形態において、GITRアゴニストは、抗GITR抗体分子である。一実施形態において、GITRアゴニストは、全体として参照により援用される「Compositions and Methods of Use for Augmented Immune Response and Cancer Therapy」という名称の2016年4月14日に公開された国際公開第2016/057846号パンフレットにおいて記載されるとおりの抗GITR抗体分子である。
一実施形態において、抗GITR抗体分子は、BMS 986156又はBMS986156としても知られるBMS−986156(Bristol−Myers Squibb)である。BMS−986156及び他の抗GITR抗体は、例えば、全体として参照により援用される米国特許第9,228,016号明細書及び国際公開第2016/196792号パンフレットにおいて開示される。一実施形態において、抗GITR抗体分子は、例えば、表10に開示されるとおりのBMS−986156のCDR配列の1つ以上(又は一括して全てのCDR配列)、重鎖若しくは軽鎖可変領域配列又は重鎖若しくは軽鎖配列を含む。
特定の実施形態において、本明細書に記載される組み合わせは、トランスフォーミング増殖因子ベータ(本明細書で同義的に使用されるTGF−β、TGFβ、TGFb又はTGF−ベータとしても知られる)阻害剤を含む。
一部の実施形態において、TGF−β阻害剤は、XOMA 089又は全体として参照により援用される国際出願公開国際公開第2012/167143号パンフレットに開示される化合物を含む。
(国際公開第2012/167143号パンフレットの配列番号6として開示される)のアミノ酸配列を有する。XOMA 089の軽鎖可変領域は、
(国際公開第2012/167143号パンフレットの配列番号8として開示される)のアミノ酸配列を有する。
一部の実施形態において、TGF−β阻害剤は、フレソリムマブ(CAS登録番号:948564−73−6)を含む。フレソリムマブは、GC1008としても知られる。フレソリムマブは、TGF−ベータアイソフォーム1、2及び3に結合し且つ阻害するヒトモノクローナル抗体である。
特定の実施形態において、本明細書に記載される組み合わせは、IL−15/IL−15Ra複合体を含む。一部の実施形態において、IL−15/IL−15Ra複合体は、NIZ985(Novartis)、ATL−803(Altor)又はCYP0150(Cytune)から選択される。一部の実施形態において、IL−15/IL−15RA複合体は、NIZ985である。理論に束縛されるものではないが、一部の実施形態において、IL−15は、ナチュラルキラー細胞を強めて、例えば増強して、膵臓癌細胞を除去する、例えば死滅させると考えられる。ある実施形態において、例えば、結腸直腸癌の動物モデルにおける本明細書に記載される組み合わせ、例えばIL−15/IL15Ra複合体を含む組み合わせに対する応答、例えば治療応答は、ナチュラルキラー細胞浸潤と関連する。
一実施形態において、IL−15/IL−15Ra複合体は、ヒトIL−15Raの可溶性形態と複合体を形成したヒトIL−15を含む。複合体は、IL−15Raの可溶性形態に共有結合的又は非共有結合的に結合されたIL−15を含み得る。特定の実施形態において、ヒトIL−15は、IL−15Raの可溶性形態に非共有結合的に結合される。特定の実施形態において、組成物のヒトIL−15は、表11における配列番号1001のアミノ酸配列を含み、ヒトIL−15Raの可溶性形態は、全体として参照により援用される国際公開第2014/066527号パンフレットに記載されるとおりの表11における配列番号1002のアミノ酸配列を含む。本明細書に記載される分子は、全体として参照により援用される国際公開第2007/084342号パンフレットに記載されるベクター、宿主細胞及び方法によって作製され得る。
一実施形態において、IL−15/IL−15Ra複合体は、ALT−803、IL−15/IL−15Ra Fc融合タンパク質(IL−15N72D:IL−15RaSu/Fc可溶性複合体)である。ALT−803は、全体として参照により本明細書に援用される国際公開第2008/143794号パンフレットに開示される。一実施形態において、IL−15/IL−15Ra Fc融合タンパク質は、表12に開示されるとおりの配列を含む。
本発明に関して、PRRT剤は、放射性核種177Lu及びキレート剤に連結された細胞受容体結合部分によって形成される錯体である。
DOTA−OC:[DOTA0,D−Phe1]オクトレオチド、
以下の式によって表されるDOTA−TOC:[DOTA0,D−Phe1,Tyr3]オクトレオチド、エドトレオチド(INN):
DOTA−NOC:[DOTA0,D−Phe1,1−Nal3]オクトレオチド、
以下の式によって表されるDOTA−TATE:[DOTA0,D−Phe1,Tyr3]オクトレオテート、DOTA−Tyr3−オクトレオテート、DOTA−d−Phe−Cys−Tyr−d−Trp−Lys−Thr−Cys−Thr(シクロ2,7)、オキソドトレオチド(INN):
DOTA−LAN:[DOTA0,D−β−Nal1]ランレオチド、
DOTA−VAP:[DOTA0,D−Phe1,Tyr3]バプレオチド。
サトレオチドトリゾキセタン
サトレオチドテトラキセタン
本発明は、放射性核種177Lu(ルテチウム−177)及び本明細書で定義されるとおりのキレート剤に連結されたソマトスタチン受容体結合ペプチドによって形成される錯体の組み合わせ若しくは組み合わせ療法又は以下で概説されるとおりの更なる治療剤の1つと合わせた本明細書で定義されるとおりの医薬水溶液の組み合わせ若しくは組み合わせ療法を更に提供する。
一態様において、本開示は、本明細書に開示される治療剤又は癌性腫瘍の増殖が阻害若しくは減少されるように本明細書に開示される組み合わせを含む組成物若しくは製剤を含む組み合わせを使用するインビボでの対象の処置に関する。
別の態様において、本発明は、薬学的に許容可能な担体と共に製剤化される本明細書に記載される治療剤の1つ以上、例えば2、3、4、5、6、7、8つ又はそれを超えるものを含む組成物、例えば薬学的に許容可能な組成物を提供する。本明細書で使用されるとき、「薬学的に許容可能な担体」には、生理的に適合性のあるあらゆる溶媒、分散媒、等張剤及び吸収遅延剤などが含まれる。担体は、静脈内、筋肉内、皮下、非経口、直腸、脊髄又は表皮投与(例えば、注射又は注入による)に好適であり得る。
本明細書に開示される治療剤の組み合わせは、キットにおいて提供され得る。治療剤は、一般に、バイアル又は容器において提供される。適宜、治療剤は、液体又は乾燥(例えば、凍結乾燥)形態であり得る。キットは、本明細書に開示される組み合わせの治療剤の2つ以上(例えば、3、4、5つ又は全て)を含み得る。一部の実施形態において、キットは、薬学的に許容可能な希釈剤を更に含有する。治療剤は、同じ又は別個の製剤(例えば、混合物として又は別個の容器において)のキットにおいて提供され得る。キットは、1回以上の用量を提供する一定分量の治療剤を含有し得る。複数回投与のための一定分量が提供される場合、用量は、均一であるか又は異なり得る。様々な投与レジメンは、適宜、漸増又は減少され得る。組み合わせにおける治療剤の投与量は、独立して、均一であるか又は異なり得る。このキットは、使用説明書;他の試薬、例えば標識又は治療剤を標識若しくは治療剤に対してキレート化若しくは他にカップリングするのに有用な薬剤或いは放射線防護組成物;抗体を投与のために調製するための装置又は他の材料;薬学的に許容可能な担体;及び対象への投与のための装置又は他の材料を含めた1つ以上の他の要素を含み得る。
177Lu−DOTA0−Tyr3−オクトレオテート
177Lu−DOTA0−Tyr3−オクトレオテートは、既製の製品として供給される注入液のための放射性医薬品溶液である。臨床現場で必要とされる製品の操作はない。177Lu−DOTA0−Tyr3−オクトレオテートは、集約化されたGMP施設において製造され、薬物供給前にQC試験を経る。
説明
抗体溶液の必要な体積を抜き取り、静脈注射の容器に移す。
製品は保存剤を含有しない。調製後、抗体注入液を、
調製時から4時間以下にわたって室温(これは、IV容器中の注入液の室温での保管及び注入の投与のための時間を含む)、又は
注入液調製時から24時間以下にわたって2℃〜8℃(36°F〜46°F)で冷蔵下
のいずれかで保管する。凍結させない。
177Lu−DOTA0−Tyr3−オクトレオテート
177Lu−DOTA0−Tyr3−オクトレオテートは、8週間毎に投与される。177Lu−DOTA0−Tyr3−オクトレオテートの第1の用量は、抗体の1回目の投与後に2週間与えられる。各用量は、30分間かけて注入される。177Lu−DOTA0−Tyr3−オクトレオテート注入の日に静脈内ボーラスの制吐剤が与えられる(提案される選択肢:オンダンセトロン(8mg)、グラニセトロン(3mg)又はトロピセトロン(5mg))。177Lu−DOTA0−Tyr3−オクトレオテートの投与は、休日、悪天候、紛争又は同様の理由のために1日早いか又は最大1週間遅れてなされ得る。プレドニゾンは、抗PD−1療法に対する潜在的な負の効果のために予防的制吐治療として回避されるべきである。前述の制吐剤の使用に関わらず嘔気又は嘔吐があった場合、患者は、担当医の裁量で他の制吐処方で処置され得る。
抗体は、疾患進行、患者の離脱又は毒性があるまで2週間に1回投与される。抗体は、静脈内に投与され、まず組み合わせ試験において投与される。次の化合物が投与される前に30分待つ(投与経路に関係なく)。全ての用量が投与されることを確実にするため、静脈ラインを注入の最後に適切な量の希釈剤(15〜20ml)で洗い流す。抗体の投与は、休日、悪天候、紛争又は同様の理由のために1日早いか又は最大1週間遅れてなされ得る。次に、引き続く投与のタイミングを調整して、14日間隔を維持する。抗体の用量選択は、臨床プロトコル試験薬物投与の節において概説されるとおりに患者又は対象毎に割り当てられるべきである。
このプロトコルで処置を受ける任意の患者が毒性に関して評価可能となる。毒性は、NCI有害事象共通毒性規準(CTCAE)、4.03版に従って評価される。投与延期又は投与変更は、最も高い程度の毒性を示す系に従ってなされるべきである。患者が毒性のために用量の低減を有したら、用量が再び漸増されることはない。投与遅延及び投与変更は、以下の推奨を使用してなされる。
主要目的
試験の第I相部分の主要目的は、小細胞肺癌又は進行性若しくは手術不能のグレードI〜II肺性NETを有する患者において抗PD−1チェックポイント阻害剤抗体と組み合わせて与えられるとき、177Lu−DOTA0−Tyr3−オクトレオテートのRP2Dを決定することである。
抗体と組み合わせた177Lu−DOTA0−Tyr3−オクトレオテートの安全性プロファイルを特徴付けること。[第1相及び第2相部分の両方に適用可能]
〇177Lu−DOTA0−Tyr3−オクトレオテートと抗体による処置後にDCR及びORRを評価すること。
〇OSを評価すること。
〇1日目のサイクル2に得られたNETSPOT(登録商標)PETスキャンで見られる代謝応答が試験処置に対する応答を予測するかどうかを評価すること。
患者は、細胞学的又は組織学的に確認された再発若しくは難治性の進展型小細胞肺癌(ES−SCLC)、又は第一選択学療法後に進行していないES−SCLC、又は進行性若しくは手術不能のグレードI〜IIの肺性NETを有しなければならない。
患者は、細胞学的又は組織学的に確認されたES−SCLCを有していなければならず、且つ無作為化前の第一選択の白金に基づく化学療法後に進行していてはならない。
処置投与量及び投与
第I相
用量制限毒性(DLT)
DLTは、試験処置の最初の用量(1日目、サイクル1)からサイクルの最終日(57日目)までに発生する、調査中の疾患又は疾患に関連する過程に起因しない任意の毒性として定義される。DLTとみなされるには、NCI有害事象共通毒性規準(CTCAE)、4.03版に従って以下の基準の1つを満たしながら、試験薬物と関連しなければならない(属性:おそらく関連あり、関連がある可能性が高い、確実に関連あり):
●血小板に関する毒性グレード2及び任意の他のグレード3又は4の毒性であって、
〇支持療法により制御され得る場合、グレード3の下痢、嘔気又は嘔吐
〇全身性コルチコステロイド療法及び/又はホルモン置換療法の有無で管理され、患者は無症状であるグレード3の内分泌疾患を除外する。
●最適な内科治療及び>21日の処置遅延にも関わらず遷延性(>21日)の非血液学的グレードの有害事象
●任意の他の毒性:
〇ベースライン値より悪く、記述され、臨床的に関連があり且つ/又は許容できず、及び治験責任医師によってDLTであると判断される場合
〇プロトコルに定義される停止基準を引き起こす場合
〇投与スケジュールの中断を引き起こす場合
処置は、外来で施される。標準的な用量漸増フェーズI設計が使用される。3名の対象がDLTのない各用量レベルで登録される。用量漸増の詳細については、下の表を参照されたい。
177Lu−DOTA0−Tyr3−オクトレオテートの以下の用量レベルは、抗体と組み合わせて探索され得る(表2):
●用量レベル−1(開始用量):3.7GBq(100mCi)
●用量レベル 0:7.4GBq(200mCi)
177Lu−DOTA0−Tyr3−オクトレオテートは、8週間毎に合計で4用量与えられる。
ある用量レベル内の3名の患者は、次のより高い用量レベルへの自然増加が始まり得る前に1サイクル(56日)にわたって観察されなければならない。患者が、離脱前にDLTを経験することなく56日の療法を完了する前に試験から離脱する場合、追加の患者がその用量レベルに追加され得る。
第II相部分は、177Lu−DOTA0−Tyr3−オクトレオテート及び抗体による組み合わせ療法の開始時に疾患進行を有しない(奏効例及び安定疾患)、白金に基づく標準的な第一選択の化学療法(例えば、白金とエトポシド又はイリノテカンの4〜6サイクル)を完了したES−SCLCを有する患者からなるであろう。次に、適格な患者は、2つのアームに無作為に割り当てられる:一方は、177Lu−DOTA0−Tyr3−オクトレオテート及び抗体の組み合わせにより処置され、且つ他方のアームは、標準的な化学療法処置の完了後にフォロー(観察)が継続される。化学療法後に放射線療法を受けていない患者に関して、無作為化は、最後の化学療法サイクルの6週間以内に行われなければならない。試験処置は、無作為化から2週間以内に開始されなければならない。化学療法後に放射線療法(予防的な頭蓋放射線照射及び/又は胸部放射線照射を含む)を受ける患者に関して、無作為化は、最後の化学療法サイクルの9週間以内であるが、放射線療法の完了の少なくとも2週間後に行われなければならず、177Lu−DOTA0−Tyr3−オクトレオテートの最初の用量を放射線療法の8週間以内に与えることはできない。
●インフォームドコンセントのフォーム(ICF)に署名した全ての患者に関して、スクリーニング番号が、現場で利用可能な最も小さい番号で始まる時系列の順序に割り当てられる。
●患者は、施設番号(4桁)及びスクリーニング番号(3桁)で構成される固有の患者識別番号(患者ID No.)によって特定される。
●e−CRFは、患者に固有の無作為化番号を割り当てられ、これは、処置アームに患者を結びつけるために使用される。
●無作為化は、NETSPOT(登録商標)PET腫瘍取込みスコア(グレード2、3及び4)に従って層別化される。
スクリーニング/ベースライン手順
全ての適格性基準を満たす対象は、試験に登録される。この試験に対する適格性を決定するために排他的に実施される評価は、インフォームドコンセントを取得した後になされる。臨床的適応のために実施される評価(試験の適格性を排他的には決定しない)は、たとえ試験がインフォームドコンセントを取得する前になされたとしても、ベースライン値のために使用され得る。全てのスクリーニング手順は、特に明記しない限り、試験薬物を開始する前の4週間以内に実施されなければならない。スクリーニング手順は、以下を含む。
●完全な病歴及び生命徴侯、身長、体重及びECOGパフォーマンススコアを含む身体検査。
●ベースライン画像検査:患者は、胸部/腹部/骨盤のコンピューター断層撮影(CT)スキャン、脳のMRI又はCT及びFDG−PET(頭蓋底から大腿中部)によるベースラインラジオグラフ評価を有するべきである。2回のNETSPOT(登録商標)PETスキャンが実施され、1回目は、化学療法の開始前の4週間以内(好ましい)又は化学療法の開始直後である。このスキャンを使用して、SSTR2発現及びこの試験に対する患者の適格性を評価する。2回目のNETSPOT(登録商標)PETスキャンは、可能な限り、化学療法の終了時から実施される(理想的には試験処置の開始前の1週間以内)。このスキャンは、化学療法による最終的なSSTR2発現の改変に対する探索性分析のために使用される。患者が化学療法の完了後に存在し、且つ化学療法前又は化学療法中に実施されるNETSPOT(登録商標)PETスキャンを有しなかった場合、NETSPOT(登録商標)PETスキャンは、患者の適格性を決定するために取得される。外部の画像検査は、PIの裁量で受け入れられる。
●心電図(EKG)
●臨床検査(別段の記載がない限り、処置の開始前の1週間以内に得られるベースライン試験)
〇血液学的プロファイル:白血球百分率及び血小板数を伴う全血球数(CBC)、プロトロンビン時間/国際標準比(PT/INR)、活性化部分トロンボプラスチン時間(aPTT)。
〇生化学的プロファイル:ナトリウム、カリウム、カルシウム、リン、マグネシウム、血液尿素窒素(BUN)、クレアチニン、グルコース、アスパラギン酸アミノトランスフェラーゼ(AST)、アラニンアミノトランスフェラーゼ(ALT)、アルカリホスファターゼ、乳酸デヒドロゲナーゼ(LDH)、ビリルビン、アルブミン。
〇ベースライン糸球体濾過率(GFR)計算。
〇試験薬物の開始前の24時間以内の妊娠可能年齢の女性患者に関する血清又は尿ベータ−hCG。
〇ウイルスマーカー:処置開始前の3ヶ月以内のHBsAg、抗HCV、抗HIV。
〇アミラーゼ、リパーゼ、甲状腺機能試験(TSH、遊離T3、遊離T4)。
試験処置を受けている患者は、2週間毎にフォローされ、以下が行われる(別段の指示がない限り)。
●病歴及び身体検査。
●臨床検査:血液学的プロファイル(白血球百分率を伴うCBC)。生化学的プロファイル。
●甲状腺機能試験は、抗体を受容している対象に関しておよそ4週間毎になされる。
●腫瘍イメージングは、8週間毎に実施される(次のサイクルを開始する1週間以内)。
●代謝応答を評価するためのサイクル2の1日目(±3日)におけるNETSPOT(登録商標)PETスキャン。
●177Lu−DOTA0−Tyr3−オクトレオテートの投与前の24時間以内の妊娠可能年齢の女性患者に関する血清又は尿ベータ−hCG。
●病歴及び身体検査。
●臨床検査:血液学的及び生化学的プロファイル。
●腫瘍イメージングは、8週間毎に実施される。
●病歴及び身体検査。
●臨床検査:血液学的及び生化学的プロファイル。甲状腺機能試験。
本明細書において言及される全ての刊行物、特許及び受託番号は、各個別の刊行物又は特許が参照によって援用されることが具体的且つ個別的に指示されたものとして本明細書によって全体として参照により援用される。
本発明の具体的な実施形態が考察されているが、上記の本明細書は、例示的なものであり、限定的なものではない。本明細書及び以下の特許請求の範囲を検討すれば、当業者に本発明の多くの変形形態が明らかになるであろう。本発明の完全な範囲は、その均等物の全範囲と併せた特許請求の範囲及びかかる変形形態と併せた本明細書を参照することにより決定されなければならない。
Claims (19)
- 対象におけるソマトスタチン受容体過剰発現癌を処置する際に使用するための、ペプチド受容体放射性核種治療(PRRT)剤及び1つ又は2つの癌免疫(I−O)治療剤を含む組み合わせであって、前記I−O治療剤は、LAG−3阻害剤、TIM−3阻害剤、GITRアゴニスト、TGF−β阻害剤、IL15/IL−15RA複合体及びPD−1阻害剤からなる群から選択され、前記PD−1阻害剤は、スパルタリズマブ、ペムブロリズマブ、ピディリズマブ、デュルバロマブ、アテゾリズマブ、アベルマブ、MEDI0680、REGN2810、TSR−042、PF−06801591、BGB−A317、BGB−108、INCSHR1210及びAMP−224からなる群から選択される、組み合わせ。
- 対象におけるソマトスタチン受容体過剰発現癌を処置する方法であって、ペプチド受容体放射性核種治療(PRRT)剤及び1つ又は2つの癌免疫(I−O)治療剤の組み合わせを前記対象に投与することを含み、前記I−O治療剤は、LAG−3阻害剤、TIM−3阻害剤、GITRアゴニスト、TGF−β阻害剤、IL15/IL−15RA複合体及びPD−1阻害剤からなる群から選択され、前記PD−1阻害剤は、スパルタリズマブ、ペムブロリズマブ、ピディリズマブ、デュルバロマブ、アテゾリズマブ、アベルマブ、MEDI0680、REGN2810、TSR−042、PF−06801591、BGB−A317、BGB−108、INCSHR1210及びAMP−224からなる群から選択される、方法。
- 前記PRRT剤は、放射性核種ルテチウム−177(177Lu)及びキレート剤に連結されたソマトスタチン受容体結合分子を含む、請求項1に記載の使用のための組み合わせ又は請求項2に記載の方法。
- 前記ソマトスタチン受容体結合分子は、オクトレオチド、オクトレオテート、ランレオチド、バプレオチド、パシレオチド及びサトレオチドからなる群から選択される、請求項3に記載の使用のための組み合わせ又は方法。
- 前記キレート剤は、1,4,7,10−テトラアザシクロドデカン−1,4,7,10−四酢酸(DOTA)である、請求項4に記載の使用のための組み合わせ又は方法。
- 前記キレート剤に連結された前記ソマトスタチン受容体結合分子は、DOTA−OC:[DOTA0,D−Phe1]オクトレオチド、DOTA−TOC:[DOTA0,D−Phe1,Tyr3]オクトレオチド(即ちエドトレオチド)、DOTA−NOC:[DOTA0,D−Phe1,1−Nal3]オクトレオチド、DOTA−TATE:[DOTA0,D−Phe1,Tyr3]オクトレオテート(即ちオキソドトレオチド)、DOTA−LAN:[DOTA0,D−β−Nal1]ランレオチド、DOTA−VAP:[DOTA0,D−Phe1,Tyr3]バプレオチド、サトレオチド、トリゾキセタン及びサトレオチドテトラキセタンからなる群から選択される、請求項3に記載の使用のための組み合わせ又は方法。
- 前記PRRT剤は、ルテチウム(177Lu)オキソドトレオチド(即ち177Lu[DOTA0,D−Phe1,Tyr3]オクトレオテート)である、請求項1に記載の使用のための組み合わせ又は請求項2に記載の方法。
- 前記PRRT剤は、
(a)錯体であって、
(ai)放射性核種177Lu(ルテチウム−177)であって、それが250〜500MBq/mLの容積測定による放射能を提供する濃度における放射性核種177Lu(ルテチウム−177)、及び
(aii)DOTAが連結されたソマトスタチン受容体結合ペプチド
によって形成される錯体;
(b)放射線分解に対する安定剤、(bi)0.5〜1mg/mLの濃度のゲンチシン酸、及び(bii)2.0〜5.0mg/mLの濃度のアスコルビン酸;
(c)0.01〜0.10mg/mLの濃度のジエチレントリアミン五酢酸(DTPA)又はその塩;及び
(d)酢酸緩衝液であって、
(di)0.3〜0.7mg/mLの濃度の酢酸;及び
(dii)0.4〜0.9mg/mLの濃度の酢酸ナトリウム
で構成され、好ましくは、4.5〜6.0のpH、好ましくは5.0〜5.5のpHを提供する酢酸緩衝液
を含む医薬水溶液として製剤化される、請求項3〜7のいずれか一項に記載の使用のための組み合わせ又は方法。 - ゲンチシン酸は、成分(ai)及び(aii)の錯体形成中に存在し、且つアスコルビン酸は、成分(ai)及び(aii)の錯体形成後に加えられる、請求項8に記載の使用のための組み合わせ又は方法。
- 前記LAG−3阻害剤は、LAG525、BMS−986016又はTSR−033から選択される、請求項1、3〜9のいずれか一項に記載の使用のための組み合わせ又は請求項2〜9のいずれか一項に記載の方法。
- 前記TIM−3阻害剤は、MBG453又はTSR−022である、請求項1、3〜10のいずれか一項に記載の使用のための組み合わせ又は請求項2〜10のいずれか一項に記載の方法。
- 前記GITRアゴニストは、GWN323、BMS−986156、MK−4166、MK−1248、TRX518、INCAGN1876、AMG 228又はINBRX−110から選択される、請求項1、3〜11のいずれか一項に記載の使用のための組み合わせ又は請求項2〜11のいずれか一項に記載の方法。
- 前記TGF−β阻害剤は、XOMA 089又はフレソリムマブである、請求項1、3〜12のいずれか一項に記載の使用のための組み合わせ又は請求項2〜12のいずれか一項に記載の方法。
- 前記IL−15/IL−15RA複合体は、NIZ985、ATL−803又はCYP0150から選択される、請求項1、3〜13のいずれか一項に記載の使用のための組み合わせ又は請求項2〜13のいずれか一項に記載の方法。
- 1つ又は2つの更なる抗癌剤を含む、請求項1、3〜14のいずれか一項に記載の使用のための組み合わせ又は請求項2〜14のいずれか一項に記載の方法。
- 前記更なる抗癌剤は、オクトレオチド、ランレオチド、バプロレオチド、パシレオチド、サトレオチド、エベロリムス、テモゾロミド、テロトリスタット、スニチニブ、サルファチニブ、リボシクリブ、エンチノスタット及びパゾパニブからなる群から選択される、請求項15に記載の使用のための組み合わせ又は方法。
- 前記ソマトスタチン受容体過剰発現癌は、神経内分泌腫瘍(NET)である、請求項1、3〜16のいずれか一項に記載の使用のための組み合わせ又は請求項2〜13のいずれか一項に記載の方法。
- 前記神経内分泌腫瘍(NET)は、胃腸膵神経内分泌腫瘍、カルチノイド腫瘍、褐色細胞腫、傍神経節腫、甲状腺髄様癌、肺性神経内分泌腫瘍、胸腺神経内分泌腫瘍、カルチノイド腫瘍又は膵性神経内分泌腫瘍、下垂体腺腫、副腎腫瘍、メルケル細胞癌、乳癌、非ホジキンリンパ腫、ホジキンリンパ腫、頭頸部腫瘍、尿路上皮癌(膀胱)、腎細胞癌、肝細胞癌、GIST、神経芽細胞腫、胆管腫瘍、子宮頸部腫瘍、ユーイング肉腫、骨肉腫、小細胞肺癌(SCLC)、前立腺癌、黒色腫、髄膜腫、神経膠腫、髄芽腫、血管芽腫、テント上原始、神経外胚葉性腫瘍及び感覚神経芽腫からなる群から選択される、請求項17に記載の使用のための組み合わせ又は方法。
- 前記神経内分泌腫瘍(NET)は、機能性カルチノイド腫瘍、インスリノーマ、ガストリン産生腫瘍、血管作用性小腸ペプチド(VIP)腫、グルカゴン産生腫瘍、セロトニノーマ、ヒスタミノーマ、ACTH腫、褐色細胞腫及びソマトスタチン産生腫瘍からなる群から選択される、請求項17に記載の使用のための組み合わせ又は方法。
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Title |
---|
"LUTATHERA (LUTETIUM LU 177 DOTATATE) INJECTION、PRINTED LABELING"、[ONLINE], JPN6023026012, 12 March 2018 (2018-03-12), ISSN: 0005092431 * |
ANDREWS, LAWRENCE P. ET AL.: "LAG3 (CD223) as a cancer immunotherapy target", IMMUNOLOGICAL REVIEWS, vol. 276, JPN6023026013, 2017, pages 80 - 96, XP002781851, ISSN: 0005092430, DOI: 10.1111/imr.12519 * |
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