JP2012514651A - 抗CD30vc−PAB−MMAE抗体−薬物コンジュゲートのウィークリー投与計画 - Google Patents
抗CD30vc−PAB−MMAE抗体−薬物コンジュゲートのウィークリー投与計画 Download PDFInfo
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- JP2012514651A JP2012514651A JP2011545458A JP2011545458A JP2012514651A JP 2012514651 A JP2012514651 A JP 2012514651A JP 2011545458 A JP2011545458 A JP 2011545458A JP 2011545458 A JP2011545458 A JP 2011545458A JP 2012514651 A JP2012514651 A JP 2012514651A
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Abstract
Description
本発明は、とりわけ、CD30発現血液癌の治療方法を提供する。本発明者らは、抗CD30抗体−薬物コンジュゲートcAC10−(MC−vc−PAB−MMAE)4を、約0.8mg/kg〜約1.2mg/kg用量で用いるウィークリー治療計画が、驚くほど有効な治療計画であることを見出した。この治療計画によれば、例えば、短期間で多くの客観的奏効があらわれ、また、頻繁な投薬にもかかわらず、許容できる耐薬プロファイルを有するようになる。このように実質的な用量の抗体−薬物コンジュゲートをかかる頻繁な間隔で投与することができ、その結果高い奏効率と許容できる毒性プロファイルとが得られることは驚くべき知見である。第I相試験では、治療から8週間以内に多くの完全寛解が観察された。このウィークリー投与計画では、短期間で高い奏効率がもたらされることが観察されている。高奏効率であることはまた、癌治療に対して併用療法ではなく、単剤療法として送達される薬物にとって驚くべくことである。したがって、本発明の方法では、とりわけ、被験者に対して、抗CD30vc−PAB−MMAE抗体−薬物コンジュゲートを投与するウィークリー投与計画が提供される。ある実施形態では、このウィークリー投与計画は、他の投与計画と比較して(例えば、3週間毎の投与計画と比較して)、被験者の治療に対する奏効率を高める。ある実施形態において、本投与計画は、治療サイクルにわたる抗体−薬物コンジュゲートの総量が、他の投与計画と比較して、このウィークリー投与計画では多いかもしれないという事実にもかかわらず、他の投与計画と比較して(例えば、3週間毎の投与計画と比較して)、被験者が有害事象(用量制限毒性を含む)を蒙る確率を高めない。本発明はまた、とりわけ、ウィークリー投与計画後の維持療法も提供する。
本発明は、とりわけ、cAC10−MC−vc−PAB−MMAE抗体−薬物コンジュゲート(Sanderson et al.,Clinical Cancer Research 2005,11:843−852。この文献は参照によりその全体が全ての目的で本明細書に組み込まれる)の毎週投与が、許容できる耐薬プロファイルとともに、驚くほど高い奏効率をもたらすことを見出したことに基づくものである。
特に他で定義しない限り、本明細書中で用いる全ての技術・科学用語は、記載されている方法及び組成物に関係する技術分野の当業者が一般に理解している意味と同じ意味を有する。本明細書では、以下の用語及び語句は、特に他で規定されなければ、それらに帰因する意味を有する。
本発明は、とりわけ、CD30発現血液癌の治療のための投与計画を提供する。この投与計画は、本明細書に記載のとおり、体重あたり約0.8mg/kg〜約1.8mg/kg、0.8mg/kg〜約1.6mg/kg、0.8mg/kg〜約1.4mg/kg、0.8mg/kg〜約1.2mg/kg、又はより好ましくは約0.8mg/kg〜約1.0mg/kgの週用量の抗体−薬物コンジュゲートを、少なくとも3週間(例えば、21日間)の期間で投与することを含む。週用量は、単回週用量(週に1回)として、あるいは分割送達(例えば、週に2回以上)により投与され得る。
本発明の方法は、CD30発現血液癌の治療のために被験者に抗CD30vc−PAB−MMAE抗体−薬物コンジュゲートを投与することを包含する。被験者への抗体−薬物コンジュゲートの投与及びCD30発現癌細胞への抗CD30抗体の結合の後、抗体−薬物コンジュゲートは細胞内に取り込まれ、薬物が放出される。
本発明の組成物及び方法での使用に適している抗CD30抗体は、CD30抗原と特異的に結合する任意の抗体を含む。
本明細書に記載された方法は、vc−PABリンカーを介してMMAEに共有結合している抗CD30抗体を含んでなる抗体−薬物コンジュゲートの使用を包含する。抗体−薬物コンジュゲートは、医薬組成物として被験者に投与される。
ここで、
mAbは、抗CD30抗体であり、
Sは、抗体の硫黄原子であり、
Aは、ストレッチャー単位であり、
pは、約3から約5である。
様々な送達システムを抗体−薬物コンジュゲートの投与に用いることができる。本発明のある好ましい実施形態では、抗体−薬物コンジュゲート化合物の投与は、静脈内投与による。ある実施形態では、投与は、2時間の静脈内投与による。
本発明はまた、CD30発現血液癌の治療のためのキットも提供する。キットは、抗体−薬物コンジュゲートが入った容器を含む。このようなキットは、当業者にとって容易に明らかであるように、必要に応じて、1つ以上の様々な慣用の医薬キット成分、例えば、1つ以上の製薬上許容される担体を含む容器、追加の容器等をさらに含んでいてもよい。投与すべき成分の量、投与についてのガイドライン、及び/又は各種成分の混合についてのガイドラインを示す印刷された使用説明書を、挿入物又はラベルとして、キットに含めてもよい。
Claims (25)
- 前記CD30発現血液癌は、ホジキンリンパ腫である、請求項1に記載の方法。
- 前記CD30発現血液癌は、未分化大細胞型リンパ腫である、請求項1に記載の方法。
- 前記週用量は、約0.8mg/kg〜約1.0mg/kgである、請求項1に記載の方法。
- 前記週用量は、約0.8mg/kgである、請求項1に記載の方法。
- 前記週用量は、約1mg/kgである、請求項1に記載の方法。
- 前記週用量は、約1.2mg/kgである、請求項1に記載の方法。
- 前記週用量は、単回週用量である、請求項1〜7のいずれかに記載の方法。
- 前記医薬組成物を、各治療サイクル間に1週間の休息期間を有する21日間の治療サイクルで、少なくとも2回投与する、請求項1〜8のいずれかに記載の方法。
- 前記医薬組成物を、少なくとも1回の28日間の治療サイクルの間4週のうち3週連続して投与する、請求項1〜8のいずれかに記載の方法。
- 前記医薬組成物を、少なくとも2回の28日間の治療サイクルの間4週のうち3週連続して投与する、請求項1〜8のいずれかに記載の方法。
- 少なくとも2回の28日間の治療サイクル後、請求項1に記載の医薬組成物を維持療法として投与することをさらに含む、請求項11に記載の方法。
- 前記維持療法は、被験者が検出可能な癌を有していないことを示す評価後に開始される、請求項12に記載の方法。
- 前記維持療法は、請求項1に記載の医薬組成物を3〜6週毎に1回投与することを含む、請求項12又は13に記載の方法。
- 前記維持療法のための抗体−薬物コンジュゲートの投与量は、体重1kgあたり約1mg/kg〜約1.8mg/kgである、請求項12〜14のいずれかに記載の方法。
- 前記被験者は、再発性又は難治性のCD30発現血液癌を有する、請求項1〜15のいずれかに記載の方法。
- pが、約4である、請求項17に記載の方法。
- Sが、抗体のシステイン残基の硫黄原子である、請求項1〜18のいずれかに記載の方法。
- 前記抗CD30抗体が、キメラAC10抗体であるか、又はマウスAC10抗体との結合を競合する、請求項1〜19のいずれかに記載の方法。
- 前記抗CD30抗体が、キメラAC10抗体である、請求項20に記載の方法。
- (i)約1〜25mg/mlの請求項1に記載の抗体−薬物コンジュゲート、(ii)クエン酸緩衝液、リン酸緩衝液、若しくはヒスチジン緩衝液、又はそれらの組合せから選択される、約5〜50mMの緩衝液、(iii)約3%〜約10%のスクロース、若しくはトレハロース、又はこれらの組合せ、(iv)任意に、ポリソルベート20、若しくはポリソルベート80、又はこれらの組合せから選択される、約0.05〜2mg/mlの界面活性剤、及び(v)水を含んでなり、pHが約5.3〜約7である、医薬組成物。
- (i)約1〜25mg/mlの請求項1に記載の抗体−薬物コンジュゲート、(ii)クエン酸緩衝液、リン酸緩衝液、若しくはヒスチジン緩衝液、又はそれらの組合せから選択される、約5〜50mMの緩衝液、(iii)約3%〜約10%のスクロース、若しくはトレハロース、又はこれらの組合せ、(iv)任意に、ポリソルベート20、若しくはポリソルベート80、又はこれらの組合せから選択される、約0.05〜2mg/mlの界面活性剤、及び(v)水から本質的に成り、pHが約5.3〜約7である、医薬組成物。
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019524713A (ja) * | 2016-07-08 | 2019-09-05 | ゲンマブ エー/エス | 抗axl抗体に基づく抗体薬物コンジュゲートのための新しい投薬レジメン |
JP2019206514A (ja) * | 2018-04-13 | 2019-12-05 | ジェネンテック, インコーポレイテッド | 安定した抗cd79bイムノコンジュゲート製剤 |
JP2022513684A (ja) * | 2018-12-03 | 2022-02-09 | アジェンシス,インコーポレイテッド | 抗191p4d12抗体薬物コンジュゲートを含む薬学的組成物、およびその使用方法 |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3545969B1 (en) | 2009-01-09 | 2023-12-13 | Seagen Inc. | Dosing regimens for anti-cd30 vc-pab-mmae antibody drug-conjugates |
US8758758B1 (en) * | 2010-01-08 | 2014-06-24 | Seattle Genetics, Inc. | Post-relapse treatment of CD30 expressing lymphomas |
WO2012054748A2 (en) * | 2010-10-22 | 2012-04-26 | Seattle Genetics, Inc. | Synergistic effects between auristatin-based antibody drug conjugates and inhibitors of the pi3k-akt mtor pathway |
EP2812702B1 (en) | 2012-02-10 | 2019-04-17 | Seattle Genetics, Inc. | Diagnosis and management of CD30-expressing cancers |
US9801951B2 (en) | 2012-05-15 | 2017-10-31 | Concortis Biosystems, Corp. | Drug-conjugates, conjugation methods, and uses thereof |
US9353150B2 (en) | 2012-12-04 | 2016-05-31 | Massachusetts Institute Of Technology | Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment |
EP3620470B1 (en) | 2013-10-11 | 2023-07-26 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Tem8 antibodies and their use |
RU2016134258A (ru) | 2013-10-15 | 2018-02-28 | Сорренто Терапьютикс Инк. | Конъюгат лекарственного средства с направляющей молекулой и двумя различными лекарственными средствами |
SG11201600954XA (en) | 2013-10-15 | 2016-03-30 | Seattle Genetics Inc | Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics |
EP3076963A4 (en) * | 2013-12-06 | 2017-09-13 | Millennium Pharmaceuticals, Inc. | Combination of aurora kinase inhibitors and anti-cd30 antibodies |
EP3160513B1 (en) | 2014-06-30 | 2020-02-12 | Glykos Finland Oy | Saccharide derivative of a toxic payload and antibody conjugates thereof |
CN107849090A (zh) | 2015-01-28 | 2018-03-27 | 索伦托医疗有限公司 | 抗体药物偶联物 |
WO2017042352A1 (en) | 2015-09-11 | 2017-03-16 | Genmab A/S | Dosing regimens for anti-tf-antibody drug-conjugates |
US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
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US11464869B2 (en) | 2016-11-14 | 2022-10-11 | Takeda Pharmaceutical Company Limited | Non-adult human dosing of brentuximab vedotin |
WO2018175994A1 (en) | 2017-03-24 | 2018-09-27 | Seattle Genetics, Inc. | Process for the preparation of glucuronide drug-linkers and intermediates thereof |
US11932650B2 (en) | 2017-05-11 | 2024-03-19 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
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TW201922281A (zh) | 2017-10-11 | 2019-06-16 | 美商西雅圖遺傳學公司 | 降低抗cd30抗體藥物綴合物療法之副作用之方法 |
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US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
AU2018359546A1 (en) | 2017-11-01 | 2020-05-28 | Seagen Inc. | Methods of reducing side effects of anti-CD30 antibody drug conjugate therapy |
WO2019183438A1 (en) | 2018-03-23 | 2019-09-26 | Seattle Genetics, Inc. | Use of antibody drug conjugates comprising tubulin disrupting agents to treat solid tumor |
DE102019109435A1 (de) * | 2018-06-22 | 2019-12-24 | Schaeffler Technologies AG & Co. KG | Antriebsstrangeinheit für ein Hybridfahrzeug mit Schwingungstilger |
SG11202103342QA (en) | 2018-10-01 | 2021-04-29 | Seagen Inc | Methods of treating peripheral t cell lymphoma using anti-cd30 antibody drug conjugate therapy |
WO2020247054A1 (en) | 2019-06-05 | 2020-12-10 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
AU2020299382A1 (en) | 2019-07-02 | 2022-01-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Monoclonal antibodies that bind EGFRvIII and their use |
US20220347313A1 (en) | 2019-09-25 | 2022-11-03 | Seagen, Inc. | Combination Anti-CD30 ADC, Anti-PD-1 and Chemotherapeutic for Treatment of Hematopoietic Cancers |
IL292685A (en) | 2019-11-04 | 2022-07-01 | Seagen Inc | Anti-cd30 drug-antibody conjugates and their use in the treatment of HIV infection |
US20230090868A1 (en) | 2020-01-31 | 2023-03-23 | Seagen Inc. | Anti-cd30 antibody-drug conjugates and their use for the treatment of non-hodgkin lymphoma |
AU2021273256A1 (en) | 2020-05-13 | 2022-12-15 | Seagen Inc. | Methods of treating cancer using a combination of anti-CD30 antibody-drug conjugates |
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KR20230158005A (ko) | 2021-03-18 | 2023-11-17 | 씨젠 인크. | 생물학적 활성 화합물의 내재화된 접합체로부터의 선택적 약물 방출 |
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KR20240099363A (ko) | 2021-10-29 | 2024-06-28 | 씨젠 인크. | 항-pd-1 항체와 항-cd30 항체-약물 접합체의 조합을 사용하여 암을 치료하는 방법 |
EP4433096A1 (en) | 2021-11-19 | 2024-09-25 | Ardeagen Corporation | Gpc3 binding agents, conjugates thereof and methods of using the same |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070166309A1 (en) * | 2002-09-27 | 2007-07-19 | Xencor, Inc. | Optimized anti-cd30 antibodies |
JP2008500961A (ja) * | 2004-03-02 | 2008-01-17 | シアトル ジェネティックス, インコーポレイテッド | 部分的に付加された抗体およびそれらの結合体化方法 |
JP2008521828A (ja) * | 2004-11-29 | 2008-06-26 | シアトル ジェネティックス, インコーポレイテッド | 操作された抗体およびイムノコンジュゲート |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040018194A1 (en) | 2000-11-28 | 2004-01-29 | Francisco Joseph A. | Recombinant anti-CD30 antibodies and uses thereof |
US7090843B1 (en) | 2000-11-28 | 2006-08-15 | Seattle Genetics, Inc. | Recombinant anti-CD30 antibodies and uses thereof |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
HUE027549T2 (hu) | 2002-07-31 | 2016-10-28 | Seattle Genetics Inc | Hatóanyagot tartalmazó konjugátumok és alkalmazásuk rák, autoimmun betegség vagy fertõzéses betegség kezelésére |
DK2489364T3 (en) | 2003-11-06 | 2015-03-02 | Seattle Genetics Inc | Monomethylvaline compounds conjugated to antibodies |
AU2005286607B2 (en) * | 2004-09-23 | 2011-01-27 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
AU2006240056B2 (en) * | 2005-04-22 | 2012-02-16 | Eli Lilly And Company | TGF Beta 1 specific antibodies |
NZ599176A (en) | 2005-08-03 | 2014-04-30 | Immunogen Inc | Immunoconjugate formulations |
KR101641345B1 (ko) * | 2007-10-12 | 2016-07-20 | 시애틀 지네틱스, 인크. | 항체-약물 접합체를 이용한 병용 요법 |
EP3545969B1 (en) | 2009-01-09 | 2023-12-13 | Seagen Inc. | Dosing regimens for anti-cd30 vc-pab-mmae antibody drug-conjugates |
US8758758B1 (en) * | 2010-01-08 | 2014-06-24 | Seattle Genetics, Inc. | Post-relapse treatment of CD30 expressing lymphomas |
-
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070166309A1 (en) * | 2002-09-27 | 2007-07-19 | Xencor, Inc. | Optimized anti-cd30 antibodies |
JP2008500961A (ja) * | 2004-03-02 | 2008-01-17 | シアトル ジェネティックス, インコーポレイテッド | 部分的に付加された抗体およびそれらの結合体化方法 |
JP2008521828A (ja) * | 2004-11-29 | 2008-06-26 | シアトル ジェネティックス, インコーポレイテッド | 操作された抗体およびイムノコンジュゲート |
Non-Patent Citations (1)
Title |
---|
BARTLETT: "A PHASE 1 MULTIDOSE STUDY OF SGN-30 IMMUNOTHERAPY IN PATIENTS WITH REFRACTORY OR RECURRENT 以下備考", BLOOD, vol. V111, JPN5012007374, 15 February 2008 (2008-02-15), pages 1848 - 1854, ISSN: 0003132293 * |
Cited By (6)
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