JP6656349B2 - 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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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 (12)
- 病期IIIb〜IVのメラノーマの治療のための医薬の製造における医薬組成物の使用であって、前記医薬組成物は、
免疫チェックポイント阻害薬と、
単純ヘルペスウイルスと
を含み、
前記免疫チェックポイント阻害薬は、抗PD1抗体又は抗CTLA−4抗体であり、
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、使用。 - 病期IIIb〜IVのメラノーマの治療のための医薬の製造における医薬組成物の使用であって、前記医薬組成物は、
免疫チェックポイント阻害薬と、
単純ヘルペスウイルスと
を含み、
前記免疫チェックポイント阻害薬は、抗CTLA−4抗体であり、
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み、
前記単純ヘルペスウイルスは、1週目の1日目に0.1mL〜4.0mLの106PFU/mLの用量で、続いて、4週目の1日目に0.1mL〜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、及び結節性腫瘍への腫瘍内注射によって投与され、前記抗CTLA−4抗体は、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、使用。 - 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又は2に記載の使用。
- 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に記載の使用。
- 前記チェックポイント阻害薬は、イピリムマブである、請求項1〜3のいずれか一項に記載の使用。
- 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のいずれか一項に記載の使用。
- 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、3又は6に記載の使用。
- 前記抗PD1抗体は、ニボルマブ、ラムブロリズマブ又はCT−011である、請求項7に記載の使用。
- 前記抗PD1抗体は、ラムブロリズマブ又はニボルマブである、請求項8に記載の使用。
- 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り、前記免疫チェックポイント阻害薬は、イピリムマブである、請求項1又は2に記載の使用。
- 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り、前記免疫チェックポイント阻害薬は、ラムブロリズマブである、請求項1に記載の使用。
- 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り、前記免疫チェックポイント阻害薬は、ニボルマブである、請求項1に記載の使用。
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EP3381942A1 (en) | 2018-10-03 |
KR102204525B1 (ko) | 2021-01-19 |
KR20150047512A (ko) | 2015-05-04 |
JP6457940B2 (ja) | 2019-01-23 |
EP3381942B1 (en) | 2021-04-14 |
CN114984062A (zh) | 2022-09-02 |
EP2890714A2 (en) | 2015-07-08 |
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WO2014036412A3 (en) | 2014-06-05 |
JP2015526525A (ja) | 2015-09-10 |
EP3981791A1 (en) | 2022-04-13 |
AU2013308595A1 (en) | 2015-03-05 |
KR20210008155A (ko) | 2021-01-20 |
PT3381942T (pt) | 2021-05-24 |
AU2018208640A1 (en) | 2018-08-09 |
CN104704002B (zh) | 2022-05-10 |
CA2881851A1 (en) | 2014-03-06 |
EA201590451A1 (ru) | 2016-05-31 |
ES2871910T3 (es) | 2021-11-02 |
HK1211601A1 (en) | 2016-05-27 |
US20150202290A1 (en) | 2015-07-23 |
AU2013308595B2 (en) | 2018-04-26 |
CN104704002A (zh) | 2015-06-10 |
US10034938B2 (en) | 2018-07-31 |
CA2881851C (en) | 2021-01-26 |
AU2013308595C1 (en) | 2019-01-17 |
AU2020201051A1 (en) | 2020-03-05 |
WO2014036412A2 (en) | 2014-03-06 |
US20190060452A1 (en) | 2019-02-28 |
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