JP2020522521A - 癌を処置するための併用療法 - Google Patents
癌を処置するための併用療法 Download PDFInfo
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Abstract
Description
本願は、2017年6月2日に出願されたPCT/CN2017/086911に基づく優先権を主張しており、この出願は、その全体が参考として援用される。
技術分野
本開示の実施形態は、上皮性腫瘍をはじめとする癌を処置するための、併用療法および関連する組成物および方法に関し、それには、上皮増殖因子受容体(EGFR)阻害剤、マイトジェン活性化プロテインキナーゼ(MEK)1/2阻害剤、およびサイクリン依存性キナーゼ(CDK)4/6阻害剤などの少なくとも2つの薬剤の組合せが含まれる。
本開示の実施形態は、適切な部分において、
(a)上皮増殖因子受容体(EGFR)阻害剤;
(b)マイトジェン活性化プロテインキナーゼ(MEK)1/2阻害剤;および
(c)サイクリン依存性キナーゼ(CDK)4/6阻害剤
から選択される2つまたはそれを超える薬剤の組合せを対象に投与することを含む、それを必要とする対象において癌を処置する方法に関する。
また、
(a)上皮増殖因子受容体(EGFR)阻害剤;
(b)マイトジェン活性化プロテインキナーゼ(MEK)1/2阻害剤;および
(c)サイクリン依存性キナーゼ(CDK)4/6阻害剤
から選択される2つまたはそれを超える薬剤の組合せを含む治療用組成物も含まれる。
また、
(a)上皮増殖因子受容体(EGFR)阻害剤;
(b)マイトジェン活性化プロテインキナーゼ(MEK)1/2阻害剤;および
(c)サイクリン依存性キナーゼ(CDK)4/6阻害剤
から選択される2つまたはそれを超える薬剤の組合せを含む患者ケアキットも含まれる。
別に定義されない限り、本明細書において使用される全ての技術用語および科学用語は、本開示が属する当業者が一般に理解する意味と同じ意味を有する。本明細書に記載のものと類似または同等の任意の方法、材料、組成物、試薬、細胞を、本開示の主題の実践または試験において使用することもできるが、好ましい方法および材料が記載されている。本明細書において引用される全ての刊行物および参考文献(特許および特許出願を含むがこれらに限定されない)は、個々の刊行物または参考文献が、完全に記載されているものとして参照により本明細書に組み込まれることが具体的かつ個別に示されているかのように、その全文が参照により本明細書に組み込まれる。本出願が優先権を主張する任意の特許出願も、刊行物および参考文献について上に記載される方法でその全文が参照により本明細書に組み込まれる。
経路および薬剤
使用方法および治療用組成物
条件付きリプログラミング細胞プールを使用する生体外(ex vivo)薬物試験
結腸直腸癌患者、肝臓癌患者、肺癌患者、膵臓癌、胃癌患者、および乳癌患者からの手術標本を、患者のコンセンサスを受け取った後に、北京癌病院および中国医学院の癌病院から入手した。患者由来の異種移植腫瘍標本は、患者からの手術腫瘍標本を接種したNod/SCIDマウスから入手した。
CI(ABC)=(AI+BI+CI−AI*BI−AI*CI−BI*CI+AI*BI*CI)/(ABCI)
CI<1である場合、AとBの組合せは相乗的である。
CI=1である場合、AとBの組合せは相加的である。
CI>1である場合、AとBの組合せは拮抗的である。
Claims (32)
- 癌の処置をそれを必要とする対象において行う方法であって、
(a)上皮増殖因子受容体(EGFR)阻害剤;
(b)マイトジェン活性化プロテインキナーゼ(MEK)1/2阻害剤;および
(c)サイクリン依存性キナーゼ(CDK)4/6阻害剤
から選択される2つまたはそれを超える薬剤の組合せを前記対象に投与することを含む方法。 - (a)が、EGFRまたはそのリガンドと特異的に結合する小分子または抗体(またはその抗原結合フラグメント)であるか、あるいは必要に応じて、セツキシマブ、パニツムマブ、ザルツムマブ、ニモツズマブ、マツズマブ、エルロチニブ、ゲフィチニブ、アファチニブ、ラパチニブ、オシメルチニブ、ブリガチニブ、およびイコチニブの1つまたは複数から選択される、請求項1に記載の方法。
- (b)が、MEK1/2またはそのリガンドと特異的に結合する小分子または抗体(またはその抗原結合フラグメント)であるか、あるいは必要に応じて、トラメチニブ、セルメチニブ、およびコビメチニブの1つまたは複数から選択される、請求項1または2に記載の方法。
- (c)が、CDK4/6またはそのリガンドと特異的に結合する小分子または抗体(またはその抗原結合フラグメント)であるか、あるいは必要に応じて、パルボシクリブ、リボシクリブ、およびアベマシクリブの1つまたは複数から選択される、請求項1から3のいずれか一項に記載の方法。
- 前記(a)と(b)の組合せを前記対象に、必要に応じて別々の組成物として、または同じ組成物の一部として一緒に投与することを含む、請求項1から4のいずれか一項に記載の方法。
- 前記(a)と(c)の組合せを前記対象に、必要に応じて別々の組成物として、または同じ組成物の一部として一緒に投与することを含む、請求項1から4のいずれか一項に記載の方法。
- 前記(a)、(b)、および(c)の組合せを前記対象に、必要に応じて別々の組成物として、または同じ組成物の一部として一緒に投与することを含む、請求項1から4のいずれか一項に記載の方法。
- 前記癌が、悪性上皮性腫瘍または癌腫である、請求項1から7のいずれか一項に記載の方法。
- 前記癌腫が、腺癌、扁平上皮癌、腺扁平上皮癌、未分化癌、大細胞癌、および小細胞癌の1または複数から選択される、請求項8に記載の方法。
- 前記癌腫が、上皮性新生物、扁平細胞新生物(扁平上皮癌)、基底細胞新生物(基底細胞癌)、移行上皮癌、腺癌(場合により、形成性胃炎、VIP産生腫瘍、胆管細胞癌、肝細胞癌、腺様嚢胞癌、腎細胞癌、またはグラヴィッツ腫瘍)、皮膚付属器新生物、粘膜表皮(nucoepidermoid)新生物、嚢胞性粘液性または漿液性新生物(a cystic, mucinous, or Serous Neoplasm)、乳腺組織関連腫瘍、腺房細胞性新生物(accinar cell neoplasm)、および複合上皮性新生物の1つまたは複数から選択される、請求項8または9に記載の方法。
- 前記癌が、結腸癌、胃癌、肺癌(場合により、小細胞肺癌または非小細胞肺癌)、乳癌、膵臓癌、口腔癌、前立腺癌、生殖細胞系の癌、直腸癌、肝癌(場合により、肝細胞癌)、腎癌(場合により、腎細胞癌)、および卵巣癌の1つまたは複数から選択される癌腫である、請求項1から10のいずれか一項に記載の方法。
- 前記(a)と(b)の組合せが、(a)および/または(b)単独と比較して、約または少なくとも約5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、200、300、400、500、600、700、800、900、1000、2000%またはそれを超えて、癌細胞の増殖を低下させ、かつ/または癌細胞の死滅を増加させる、請求項1から11のいずれか一項に記載の方法。
- 前記(a)と(b)の組合せが、(a)および/または(b)単独と比較して、癌細胞増殖を相乗的に低下させ、かつ/または癌細胞の死滅を相乗的に増加させる、請求項12に記載の方法。
- 前記(a)と(c)の組合せが、(a)および/または(c)単独と比較して、約または少なくとも約5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、200、300、400、500、600、700、800、900、1000、2000%またはそれを超えて、癌細胞の増殖を低下させ、かつ/または癌細胞の死滅を増加させる、請求項1から11のいずれか一項に記載の方法。
- 前記(a)と(c)の組合せが、(a)および/または(c)単独と比較して、癌細胞増殖を相乗的に低下させ、かつ/または癌細胞の死滅を相乗的に増加させる、請求項14に記載の方法。
- 前記(a)、(b)、および(c)の組合せが、(a)、(b)、および/または(c)単独と比較して、約または少なくとも約5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、200、300、400、500、600、700、800、900、1000、2000%またはそれを超えて、癌細胞の増殖を低下させる、請求項1から11のいずれか一項に記載の方法。
- 前記(a)、(b)、および(c)の組合せが、(a)、(b)、および/または(c)単独と比較して、癌細胞増殖を相乗的に低下させ、かつ/または癌細胞の死滅を相乗的に増加させる、請求項16に記載の方法。
- 前記(a)と(b)、(a)と(c)、または(a)、(b)、および(c)の組合せが、表E1〜E6の組合せから選択され、必要に応じて前記癌が表E1〜E6の癌細胞に対応する、請求項1から17のいずれか一項に記載の方法。
- (a)上皮増殖因子受容体(EGFR)阻害剤;
(b)マイトジェン活性化プロテインキナーゼ(MEK)1/2阻害剤;および
(c)サイクリン依存性キナーゼ(CDK)4/6阻害剤
から選択される2またはそれを超える薬剤の組合せを含む治療用組成物。 - (a)が、EGFRまたはそのリガンドと特異的に結合する小分子または抗体(またはその抗原結合フラグメント)であり、必要に応じて、セツキシマブ、パニツムマブ、ザルツムマブ、ニモツズマブ、マツズマブ、エルロチニブ、ゲフィチニブ、アファチニブ、ラパチニブ、オシメルチニブ、ブリガチニブ、およびイコチニブの1つまたは複数から選択される、請求項19に記載の治療用組成物。
- (b)が、MEK1/2またはそのリガンドと特異的に結合する小分子または抗体(またはその抗原結合フラグメント)であり、必要に応じて、トラメチニブ、セルメチニブ、およびコビメチニブの1つまたは複数から選択される、請求項19または20に記載の治療用組成物。
- (c)が、CDK4/6またはそのリガンドと特異的に結合する小分子または抗体(またはその抗原結合フラグメント)であり、必要に応じて、パルボシクリブ、リボシクリブ、およびアベマシクリブの1つまたは複数から選択される、請求項19から21のいずれか一項に記載の治療用組成物。
- 前記(a)と(b)の組合せを含む、請求項19から22のいずれか一項に記載の治療用組成物。
- 前記(a)と(c)の組合せを含む、請求項19から22のいずれか一項に記載の治療用組成物。
- 前記(a)、(b)、および(c)の組合せを含む、請求項19から22のいずれか一項に記載の治療用組成物。
- 前記(a)と(b)、(a)と(c)、または(a)、(b)、および(c)の組合せが、表E1〜E6の組合せから選択され、必要に応じて前記癌が表E1〜E6の癌細胞/組織種に対応する、請求項19から25のいずれか一項に記載の治療用組成物。
- 癌の処置をそれを必要とする対象において行うために使用するためのものである、請求項19から26のいずれか一項に記載の治療用組成物。
- 前記癌が、悪性上皮性腫瘍または癌腫である、請求項27に記載の治療用組成物。
- (a)上皮増殖因子受容体(EGFR)阻害剤;
(b)マイトジェン活性化プロテインキナーゼ(MEK)1/2阻害剤;および
(c)サイクリン依存性キナーゼ(CDK)4/6阻害剤
から選択される2またはそれを超える薬剤の組合せを含む患者ケアキット。 - 前記(a)と(b)の組合せを、必要に応じて別々の組成物として、または同じ組成物の一部として含む、請求項29に記載の患者ケアキット。
- 前記(a)と(c)の組合せを、必要に応じて別々の組成物として、または同じ組成物の一部として含む、請求項29に記載の患者ケアキット。
- 前記(a)、(b)、および(c)の組合せを、必要に応じて別々の組成物として、または同じ組成物の一部として含む、請求項29に記載の患者ケアキット。
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WO2019195959A1 (en) | 2018-04-08 | 2019-10-17 | Cothera Biosciences, Inc. | Combination therapy for cancers with braf mutation |
US11633401B2 (en) | 2018-07-06 | 2023-04-25 | Memorial Sloan Kettering Cancer Center | Combination therapy with MEK inhibitor and CDK4/6 inhibitor to treat pancreatic cancer |
WO2021068867A1 (en) * | 2019-10-09 | 2021-04-15 | Cothera Bioscience, Inc. | Combination therapy for cancers with kras mutation |
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BR112019025453A2 (pt) | 2020-06-23 |
CA3063743A1 (en) | 2018-12-06 |
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