JP6351864B2 - 癌の併用療法 - Google Patents
癌の併用療法 Download PDFInfo
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- JP6351864B2 JP6351864B2 JP2017542862A JP2017542862A JP6351864B2 JP 6351864 B2 JP6351864 B2 JP 6351864B2 JP 2017542862 A JP2017542862 A JP 2017542862A JP 2017542862 A JP2017542862 A JP 2017542862A JP 6351864 B2 JP6351864 B2 JP 6351864B2
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- Prior art keywords
- methyl
- fluoro
- oxo
- phenyl
- carboxamide
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- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
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Description
(https://clinicaltrials.gov/ct2/show/NCT01285037?term=LY2801653&rank=2)。
で示される化合物又はその医薬的に許容可能な塩と、をそのような処置を必要とする胃癌患者に投与することを含む、患者における胃癌を処置する方法が提示される。
で示される化合物又はその医薬的に許容可能な塩と、を含むキットである。
を有する化合物を指す。
1−(4−フルオロフェニル)−N−[3−フルオロ−4−[[6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イル]オキシ]フェニル]−6−メチル−2−オキソ−ピリジン−3−カルボキサミド、及び
N−[3−フルオロ−4−[1-メチル−6−(1H−ピラゾール−4−イル)インダゾール−5−イル]オキシ−フェニル]−1−(4−フルオロフェニル)−6−(ヒドロキシメチル)−2−オキソ−ピリジン−3−カルボキサミドが挙げられる。
SEQ ID NO: 1
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYD ASNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGG GTKVDIK
SEQ ID NO: 2
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVT
DAFDIWGQGTMVTVSS
SEQ ID NO: 3
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYD
ASNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGG GTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
SEQ ID NO: 4
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVT
DAFDIWGQGTMVTVSSASTKGPSVLPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTL
PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
本発明は以下を提供する。
[1]
SEQ ID NO:1の軽鎖可変領域(LCVR)アミノ酸配列及びSEQ ID NO:2の重鎖可変領域(HCVR)アミノ酸配列を含み、VEGFR2に結合する抗体の有効量と、式:
で示される化合物又はその医薬的に許容し得る塩と、をそのような処置を必要とする胃癌患者に投与することを含む、患者における胃癌を処置する方法。
[2]
前記化合物が、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミドである、請求項1に記載の方法。
[3]
前記抗体が、SEQ ID NO:3の軽鎖アミノ酸配列と、SEQ ID NO:4の重鎖アミノ酸配列と、を含み、前記抗体が、VEGFR2に結合する、請求項1に記載の方法。
[4]
前記抗体が、ラムシルマブである、請求項3に記載の方法。
[5]
前記化合物又はその塩が、約80mg/日〜約120mg/日の用量で投与される、請求項1に記載の方法。
[6]
ラムシルマブが、約6mg/kg〜約12mg/kgの用量で3週間毎に1回投与される、請求項4に記載の方法。
[7]
胃癌の処置のための、SEQ ID NO:1の軽鎖可変領域(LCVR)アミノ酸配列及びSEQ ID NO:2の重鎖可変領域(HCVR)アミノ酸配列を含み、VEGFR2に結合する抗体と、式:
で示される化合物又はその医薬的に許容し得る塩と、を含むキット。
[8]
前記抗体が、SEQ ID NO:3の軽鎖アミノ酸配列と、SEQ ID NO:4の重鎖アミノ酸配列と、を含み、前記抗体が、VEGFR2に結合する、請求項7に記載のキット。
[9]
前記抗体が、ラムシルマブである、請求項8に記載のキット。
[10]
前記化合物が、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミドである、請求項9に記載のキット。
[11]
胃癌の処置のための、1種又は複数の医薬的に許容し得る担体、希釈剤又は賦形剤を含むラムシルマブと、1種又は複数の医薬的に許容し得る担体、希釈剤又は賦形剤を含むN−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩と、を含むキット。
[12]
N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩が、錠剤である、請求項11に記載のキット。
[13]
噴霧乾燥分散体によって配合される、請求項12に記載の錠剤。
[14]
胃癌の処置における同時、分離又は連続使用のための、抗VEGFR2抗体と、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩と、を含む併用。
[15]
前記化合物又はその塩が、約80mg/日〜約120mg/日の用量で投与される、請求項14に記載の方法。
[16]
ラムシルマブが、約6mg/kg〜約12mg/kgの用量で3週間毎に1回投与される、請求項14に記載の方法。
[17]
胃癌の処置のためにN−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩との同時、分離又は連続処置において使用される抗VEGFR2抗体。
[18]
胃癌の処置のために抗VEGFR2抗体との同時、分離又は連続処置において使用されるN−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩。
[19]
前記抗VEGFR2抗体が、ラムシルマブである、請求項15又は16に記載の処置。
[20]
胃癌の処置のためにN−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩との同時、分離又は連続処置において使用されるラムシルマブ。
[21]
胃癌の処置のためにラムシルマブとの同時、分離又は連続処置において使用されるN−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩。
[22]
胃癌の処置のための薬剤の製造における抗VEGFR2抗体の使用であって、前記抗VEGFR2抗体が、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩と同時に、分離して、又は連続で投与される、使用。
[23]
胃癌の処置のための薬剤の製造におけるN−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩の使用であって、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩が、抗VEGFR2抗体と同時に、分離して、又は連続で投与される、使用。
Claims (8)
- SEQ ID NO:1の軽鎖可変領域(LCVR)アミノ酸配列及びSEQ ID NO:2の重鎖可変領域(HCVR)アミノ酸配列を含み、VEGFR2に結合する抗体の有効量と、式:
で示される化合物又はその医薬的に許容し得る塩の有効量と、を含む、患者における胃癌を処置するための医薬組成物であって、
前記抗体及び前記化合物又はその医薬的に許容し得る塩が、同時に、分離して又は連続で投与される、医薬組成物。 - 前記化合物が、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミドである、請求項1に記載の組成物。
- 前記抗体が、SEQ ID NO:3の軽鎖アミノ酸配列と、SEQ ID NO:4の重鎖アミノ酸配列と、を含む、請求項1又は2に記載の組成物。
- 前記化合物又はその塩が、約80mg/日〜約120mg/日の用量で投与され、前記抗体が、約6mg/kg〜約12mg/kgの用量で3週間毎に1回投与される、請求項1〜3のいずれか1項に記載の組成物。
- 胃癌の処置のための、SEQ ID NO:1の軽鎖可変領域(LCVR)アミノ酸配列およびSEQ ID NO:2の重鎖可変領域(HCVR)アミノ酸配列を含み、VEGFR2に結合する抗体と、式:
で示される化合物又はその医薬的に許容し得る塩と、を含むキット。 - 前記抗体が、SEQ ID NO:3の軽鎖アミノ酸配列と、SEQ ID NO:4の重鎖アミノ酸配列と、を含み、前記化合物が、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミドである、請求項5に記載のキット。
- SEQ ID NO:1の軽鎖可変領域(LCVR)アミノ酸配列及びSEQ ID NO:2の重鎖可変領域(HCVR)アミノ酸配列を含む抗VEGFR2抗体と、N−(3−フルオロ−4−(1−メチル−6−(1H−ピラゾール−4−イル)−1H−インダゾール−5−イルオキシ)フェニル)−1−(4−フルオロフェニル)−6−メチル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド又はその医薬的に許容し得る塩と、を含む胃癌の処置のための組合せ薬であって、前記抗体及び前記化合物又はその医薬的に許容し得る塩が、同時に、分離して又は連続で投与される、組合せ薬。
- 前記化合物又はその塩が、約80mg/日〜約120mg/日の用量で投与され、前記抗体が、約6mg/kg〜約12mg/kgの用量で3週間毎に1回投与される、請求項7に記載の組合せ薬。
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