JP2019065028A - 単純ヘルペスウイルスおよび免疫チェックポイント阻害薬を使用して、メラノーマを治療するための方法 - Google Patents
単純ヘルペスウイルスおよび免疫チェックポイント阻害薬を使用して、メラノーマを治療するための方法 Download PDFInfo
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Abstract
Description
本願は、35 U.S.C.119(e)の下で、2012年8月30日出願の米国特許出願第61/694,963号、および2013年7月15日出願の米国特許出願第61/846,147号の利益を主張し、それらは参照により本明細書に組み込まれる。
本研究の目的は、未治療の、切除不能な病期IIIb〜IVのメラノーマを患う対象における、用量制限毒性(DLT)の発生率によって評価されるような、イピリムマブと組み合わせたタリモジンラヘルパレプベクの安全性および忍容性を決定することであった。本研究は、非盲検、多施設、単群研究であった。イピリムマブと組み合わせたタリモジンラヘルパレプベクは、最大で18名の対象に投与される。
客観的奏効率(ORR)によって決定されるような、イピリムマブ単独と対比した、イピリムマブと組み合わせたタリモジンラヘルパレプベクの有効性の評価。
本研究の主な目的は、未治療の、切除不能な病期IIIb〜IVのメラノーマを患う患者における、全生存(OS)によって評価されるような、イピリムマブ単独と対比した、イピリムマブと組み合わせたタリモジンラヘルパレプベクの安全性および有効性を評価することである。本研究は、非盲検、多施設、無作為化研究であった。約140名の対象が以下の投与を受けるために、1:1に無作為化される。
治療群1:タリモジンラヘルパレプベク+イピリムマブ
治療群2:イピリムマブ
全奏効率、反応の持続時間、反応するまでの時間、無進行生存、切除率、1年生存率、および2年生存率によって決定されるような、イピリムマブ単独と対比した、イピリムマブと組み合わせたタリモジンラヘルパレプベクの有効性の評価。
1.対象または対象の法的に有効な代理人がインフォームドコンセントを提出している
2.悪性メラノーマの組織学的に確認された診断
3.外科的切除に適していない病期IIIb、IIIc、IVM1a、IVM1b、またはIVM1cの疾病
4.治療未経験者:切除不能な病期IIIb〜IVのメラノーマに対して、化学療法、免疫療法、または標的療法からなる任意の事前の全身性抗癌治療を受けていてはならない。注:メラノーマに対する事前の補助療法を受けた対象は除外されない。しかしながら、対象が補助療法を受けた場合、その対象は、登録(1b相)または無作為化(2相)の少なくとも6か月前に、療法を終了していなければならない。補助療法として与えられた場合でさえ、事前のタリモジンラヘルパレプベク、イピリムマブ、他のCTLA−4阻害薬、プログラム死−1(PD−1)阻害薬、または腫瘍ワクチンは許可されない。
5.以下の内の片方または両方として定義される測定可能な疾病:
少なくとも2次元で正確かつ連続的に測定され得、内臓または結節性/軟部組織疾患(リンパ節を含む)に対して、造影またはスパイラルコンピュータ断層撮影(CT)スキャンによって測定されるように、最長径が≧10mmである、少なくとも1つのメラノーマ病変
キャリパによって測定されるように、少なくとも1つの≧5mmの表層または皮下メラノーマ病変
6.以下の通り定義される、注射可能な疾病(すなわち、直接注射に好適、または超音波使用[US]ガイダンスを用いて):
最長径が≧5mmの、少なくとも1つの注射可能な皮膚、皮下、または結節性メラノーマ
7.米国東海岸がん臨床試験グループ(ECOG)の一般状態0または1
8.男性または女性、年齢≧18歳
9.以下のような十分な血液機能:
絶対好中球数(ANC)≧1.5×109/L
血小板数≧100×109/L
ヘモグロビン≧9g/dL(造血成長因子または輸血サポートの必要性なしで)
10.以下のような十分な腎機能:
血清クレアチニン≦1.5×正常上限(ULN)、または24時間クレアチニンクリアランス≧50cc/分。(注:クレアチニンクリアランスは、基準血清クレアチニンが正常範囲内にある場合、決定される必要はない)
11.以下のような十分な肝機能:
血清ビリルビン≦1.5×ULN
アスパラギン酸アミノトランスフェラーゼ(AST)≦2.5×ULN
アラニンアミノトランスフェラーゼ(ALT)≦2.5×ULN
12.プロトロンビン時間(PT)≦1.5×ULN(または国際標準化プロトロンビン比[INR]≦1.3)および部分トロンボプラスチン時間(PTT)または活性化PTT(aPTT)≦1.5×ULN
Claims (23)
- 病期IIIb〜IVのメラノーマの患者に有効量の免疫チェックポイント阻害薬および単純ヘルペスウイルスを投与することを含む、メラノーマの治療のための方法であって、前記単純ヘルペスウイルスは、機能的ICP34.5遺伝子を欠損し、機能的ICP47遺伝子を欠損し、ヒトGM−CSFをコードする遺伝子を含む、前記方法。
- 病期IIIb〜IVのメラノーマの患者の治療のために、機能的ICP34.5遺伝子を欠損し、機能的ICP47遺伝子を欠損し、ヒトGM−CSFをコードする遺伝子を含む単純ヘルペスウイルスと、免疫チェックポイント阻害薬とを含む併用治療を促進する方法。
- 機能的ICP34.5遺伝子を欠損し、機能的ICP47遺伝子を欠損し、ヒトGM−CSFをコードする遺伝子を含む単純ヘルペスウイルスと、免疫チェックポイント阻害薬とを用いた併用治療を受ける指示を与えることによって、病期IIIb〜IVのメラノーマの患者に指示して、前記患者の生存を延ばす方法。
- 機能的ICP34.5遺伝子を欠損し、機能的ICP47遺伝子を欠損し、ヒトGM−CSFをコードする遺伝子を含む単純ヘルペスウイルスと、前記単純ヘルペスウイルスと免疫チェックポイント阻害薬との組み合わせを使用することによって病期IIIb〜IVのメラノーマを治療する説明を有する添付文書またはラベルとを含むキット。
- 病期IIIb〜IVのメラノーマの患者に、1週目の1日目に最大で4.0mLの106PFU/mLの用量で、続いて、4週目の1日目に最大で4.0mLの108PFU/mLの用量で、その後、完全寛解まで2週間毎に、注射可能な皮膚、皮下、および結節性腫瘍への腫瘍内注射によって投与される単純ヘルペスウイルスと、前記単純ヘルペスウイルスの前記第3の投薬後に開始する4回の注入に関して3週間毎に3mg/kgの用量で静脈内投与される抗CTLA−4抗体とを投与することを含む、メラノーマの治療のための方法であって、前記単純ヘルペスウイルスは、機能的ICP34.5遺伝子を欠損し、機能的ICP47遺伝子を欠損し、ヒトGM−CSFをコードする遺伝子を含む、前記方法。
- 前記単純ヘルペスウイルスの前記投与は前記免疫チェックポイント阻害薬の前記投与に先行する請求項1〜5のいずれか1項に記載の方法。
- 前記チェックポイント阻害薬は抗CTLA−4抗体である請求項1〜5のいずれか1項に記載の方法。
- 前記抗CTLA−4抗体はイピリムマブである請求項7に記載の方法。
- 前記単純ヘルペスウイルスはタリモジンラヘルパレプベクである請求項1〜5のいずれか1項に記載の方法。
- 前記チェックポイント阻害薬はPD1遮断薬である請求項1〜4のいずれか1項に記載の方法。
- 前記チェックポイント阻害薬はPD−L1遮断薬である請求項1〜4のいずれか1項に記載の方法。
- 前記チェックポイント阻害薬は抗PD−L1抗体である請求項1〜4のいずれか1項に記載の方法。
- 前記チェックポイント阻害薬は抗PD1抗体である請求項1〜4のいずれか1項に記載の方法。
- 前記PD1遮断薬はニボルマブ、ラムブロリズマブ、CT−011、およびAMP−224からなる群から選択される請求項10に記載の方法。
- 前記PD−L1遮断薬はBMS−936559である請求項11に記載の方法。
- 前記促進は添付文書によるものであり、前記添付文書は免疫チェックポイント阻害薬と組み合わせて単純ヘルペスウイルスを用いる癌治療を受ける指示を与える請求項2に記載の方法。
- 前記促進は前記単純ヘルペスウイルスを含む製剤に付随する添付文書によるものである請求項2に記載の方法。
- 前記促進は医師または医療提供者への書面でのコミュニケーションによるものである請求項2に記載の方法。
- 前記促進は医師または医療提供者への口頭でのコミュニケーションによるものである請求項2に記載の方法。
- 前記促進の後に前記単純ヘルペスウイルスを用いた前記患者の前記治療が続く請求項2に記載の方法。
- 前記治療は、病期IIIb〜IVのメラノーマの患者に、1週目の1日目に最大で4.0mLの106PFU/mLの用量で、続いて、4週目の1日目に最大で4.0mLの108PFU/mLの用量で、その後、完全寛解まで2週間毎に、注射可能な皮膚、皮下、および結節性腫瘍への腫瘍内注射によって投与される単純ヘルペスウイルスと、前記単純ヘルペスウイルスの前記第3の投薬後に開始する4回の注入に関して3週間毎に3mg/kgの用量で静脈内投与される抗CTLA−4抗体とを投与することを含む請求項3に記載の方法。
- 前記病期IIIb〜IVのメラノーマを治療する前記説明は、病期IIIb〜IVのメラノーマの患者に、1週目の1日目に最大で4.0mLの106PFU/mLの用量で、続いて、4週目の1日目に最大で4.0mLの108PFU/mLの用量で、その後、完全寛解まで2週間毎に、注射可能な皮膚、皮下、および結節性腫瘍への腫瘍内注射によって投与される単純ヘルペスウイルスと、前記単純ヘルペスウイルスの前記第3の投薬後に開始する4回の注入に関して3週間毎に3mg/kgの用量で静脈内投与される抗CTLA−4抗体とを投与する指示を含む、請求項4に記載のキット。
- 請求項4に記載のキットを製造する方法。
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2018
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2020
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CA2881851C (en) | 2021-01-26 |
KR102204525B1 (ko) | 2021-01-19 |
KR20150047512A (ko) | 2015-05-04 |
US10034938B2 (en) | 2018-07-31 |
ES2871910T3 (es) | 2021-11-02 |
JP2015526525A (ja) | 2015-09-10 |
AU2013308595B2 (en) | 2018-04-26 |
AU2013308595C1 (en) | 2019-01-17 |
EA201590451A1 (ru) | 2016-05-31 |
HK1211601A1 (en) | 2016-05-27 |
US20150202290A1 (en) | 2015-07-23 |
JP6457940B2 (ja) | 2019-01-23 |
KR20210008155A (ko) | 2021-01-20 |
AU2020201051A1 (en) | 2020-03-05 |
EP3381942A1 (en) | 2018-10-03 |
AU2018208640A1 (en) | 2018-08-09 |
PT3381942T (pt) | 2021-05-24 |
WO2014036412A3 (en) | 2014-06-05 |
CN104704002B (zh) | 2022-05-10 |
EP3381942B1 (en) | 2021-04-14 |
JP6656349B2 (ja) | 2020-03-04 |
EP3981791A1 (en) | 2022-04-13 |
CN104704002A (zh) | 2015-06-10 |
WO2014036412A2 (en) | 2014-03-06 |
EP2890714A2 (en) | 2015-07-08 |
AU2013308595A1 (en) | 2015-03-05 |
CA2881851A1 (en) | 2014-03-06 |
CN114984062A (zh) | 2022-09-02 |
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