JP6224268B2 - 子宮内膜癌の治療において使用するためのデュオカルマイシンadc - Google Patents
子宮内膜癌の治療において使用するためのデュオカルマイシンadc Download PDFInfo
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Description
抗HER2 Abは抗HER2抗体または抗体断片であり、
nは0〜3、好ましくは0〜1であり、
mは1から4の平均DARを表し、
R1は
R2は
の化合物を提供し、HER2を発現しているヒト固形腫瘍は子宮内膜癌であり、特に、HER2を発現しているヒト固形腫瘍はUSCである。
インビトロでのUSC細胞株細胞毒性
9つの原発性USC細胞株は、John Wiley&Sons Ltd.により刊行されたCancer Medicine、1〜10頁、2014においてD.P.Englishらにより記載されているように、HER2表面発現についてはIHCおよびフローサイトメトリー(FACS)により、HER2遺伝子増幅についてはFISHにより評価した。
マウスにおけるインビボでのUSC細胞株異種移植片有効性
5から8週齢のメスSCIDマウス(Harlan、オランダ)に、約400μlリン酸緩衝生理食塩水溶液中、7.5×106 USC ARK−2細胞(すなわちHER2 IHC3+、FISH陽性)の単回腹腔内(i.p.)注射を与えた。腫瘍確立を可能にする7日間後、5匹のマウスの2群をSYD985(5mg/kg/週、静注)またはT−DM1(5mg/kg/週、静注)のいずれかで治療した。一般毒性の兆候はいずれの治療群においても見られなかった。全ての治療群のマウスに連続5回の注射を与え、この後マウスを追跡し、主要転帰としての全生存を観察した。
マウスにおけるインビボでのUSC細胞株異種移植片有効性研究
USC ARK−2細胞(すなわちHER2 IHC3+、FISH陽性)を培養拡大し、洗浄し、700万細胞の濃度で5〜8週齢SCIDマウスに(Matrigel(商標)と共に)皮下的に注射した。腫瘍が体積約200mm3に達したら、群間で類似した平均腫瘍体積を保つ5群にマウスを無作為に分けた。各群に合計8〜10匹がいた。
以下に、本願の種々の実施態様を付記する。
[1]
HER2を発現しているヒト固形腫瘍の治療において使用するための、式(I)
抗HER2 Abは抗HER2抗体または抗体断片であり、
nは0〜3であり、
mは1から4の平均DARを表し、
R 1 は
R 2 は
の化合物であって、前記HER2を発現しているヒト固形腫瘍が子宮内膜癌である、化合物。
[2]
抗HER2 Abは抗HER2抗体または抗体断片であり、
nは0〜1であり、
mは1から4の平均DARを表し、
R 1 は
R 2 は
[3]
式(II)
[4]
2.6から2.9の平均DARを有する、式(II)の[3]に記載の使用のための化合物。
[5]
子宮漿液性癌の治療において使用するための、[1]から[4]の何れか1に記載の化合物。
[6]
子宮内膜癌がHER2 IHC2+または1+である、[1]から[5]のいずれか一に記載の使用のための化合物。
[7]
子宮内膜癌がHER2 FISH陰性である、[1]から[6]のいずれか一に記載の使用のための化合物。
[8]
子宮内膜癌の治療において使用するための、[1]から[7]のいずれか一に記載の使用のための化合物と治療的抗体および/または化学療法剤との組合せ。
[9]
子宮漿液性癌の治療において使用するための、[8]に記載の使用のための組合せ。
[10]
前記治療的抗体がペルツズマブであり、前記化学療法剤がタキサン、アントラサイクリンまたはチロシンキナーゼ阻害剤である、[8]または[9]に記載の使用のための組合せ。
[11]
[1]から[7]のいずれか一に記載の使用のための化合物、または[8]から[10]のいずれか一に記載の使用のための組合せ、および1つ以上の薬学的に許容される賦形剤を含む医薬組成物。
[12]
凍結乾燥粉末または凍結溶液の形態の、[11]に記載の医薬組成物。
Claims (11)
- 式(I)
(式中、
抗HER2 Abは抗HER2抗体または抗体断片であり、
nは0〜3であり、
mは1から4の平均DARを表し、
R1は
R2は
- 抗HER2 Abは抗HER2抗体または抗体断片であり、
nは0〜1であり、
mは1から4の平均DARを表し、
R1は
R2は
- 式(II)
- 式(II)の化合物が2.6から2.9の平均DARを有する、請求項3に記載の医薬組成物。
- 子宮漿液性癌の治療のための、請求項1から4の何れか1項に記載の医薬組成物。
- 子宮内膜癌がHER2 IHC2+または1+である、請求項1から5のいずれか一項に記載の医薬組成物。
- 子宮内膜癌がHER2 FISH陰性である、請求項1から6のいずれか一項に記載の医薬組成物。
- 治療的抗体および/または化学療法剤と組合せて使用するための、請求項1から7のいずれか一項に記載の医薬組成物。
- 子宮漿液性癌の治療のための、請求項8に記載の医薬組成物。
- 前記治療的抗体がペルツズマブであり、前記化学療法剤がタキサン、アントラサイクリンまたはチロシンキナーゼ阻害剤である、請求項8または9に記載の医薬組成物。
- 凍結乾燥粉末または凍結溶液の形態の、請求項1から10のいずれか一項に記載の医薬組成物。
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PCT/EP2015/050332 WO2015104373A2 (en) | 2014-01-10 | 2015-01-09 | Duocarmycin adcs for use in treatment of endometrial cancer |
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AU2015205588B2 (en) | 2019-08-08 |
CL2016001743A1 (es) | 2017-01-06 |
SG11201605597VA (en) | 2016-08-30 |
RU2016132635A (ru) | 2018-02-16 |
KR20220045075A (ko) | 2022-04-12 |
JP2017502086A (ja) | 2017-01-19 |
RU2686085C2 (ru) | 2019-04-24 |
RU2016132635A3 (ja) | 2018-08-13 |
CN105899237A (zh) | 2016-08-24 |
US9427480B2 (en) | 2016-08-30 |
CA2935430C (en) | 2018-09-18 |
AU2015205588A1 (en) | 2016-07-28 |
HUE029672T2 (en) | 2017-03-28 |
DK2948183T3 (en) | 2016-06-27 |
WO2015104373A2 (en) | 2015-07-16 |
US20160008487A1 (en) | 2016-01-14 |
MX368234B (es) | 2019-09-25 |
MX2016009069A (es) | 2017-02-06 |
US20170007717A1 (en) | 2017-01-12 |
EP2948183A2 (en) | 2015-12-02 |
HRP20160797T1 (hr) | 2016-08-12 |
WO2015104373A3 (en) | 2015-09-03 |
PT2948183T (pt) | 2016-07-13 |
CA2935430A1 (en) | 2015-07-16 |
CN105899237B (zh) | 2019-09-03 |
EP2948183B1 (en) | 2016-04-06 |
US10092659B2 (en) | 2018-10-09 |
MY189713A (en) | 2022-02-28 |
ES2578831T3 (es) | 2016-08-01 |
KR20160099725A (ko) | 2016-08-22 |
CY1117712T1 (el) | 2017-05-17 |
PL2948183T3 (pl) | 2017-03-31 |
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