（遺伝子組換え）製剤及びペムブロリズマブ（遺伝子組換え）

写
⸆ ⏕ ⸆ ᑂ Ⓨ ➨ ྕ
ᖹ ᡂ ᖺ 㸰 ᭶ ᪥
㒔㐨 ᗓ ┴
ྛ ಖ ೺ ᡤ タ ⨨ ᕷ ⾨⏕୺⟶㒊㸦ᒁ㸧㛗 Ẋ
≉
ู
༊
ཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⸆ရᑂᰝ⟶⌮ㄢ㛗㸦 බ ༳ ┬ ␎ 㸧 ࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧〇๣ཬࡧ࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧〇
๣ࡢ᭱㐺౑⏝᥎㐍࢞࢖ࢻࣛ࢖ࣥ㸦㠀ᑠ⣽⬊⫵⒴ཬࡧᝏᛶ㯮Ⰽ⭘㸧࡟ࡘ࠸࡚
⤒῭㈈ᨻ㐠Ⴀ࡜ᨵ㠉ࡢᇶᮏ᪉㔪㸦ᖹᡂ ᖺ㸴᭶㸰᪥㛶㆟Ỵᐃ㸧࡟࠾
࠸࡚ࠊ㠉᪂ⓗ་⸆ရࡢ౑⏝ࡢ᭱㐺໬᥎㐍ࢆᅗࡿࡇ࡜ࡀ┒ࡾ㎸ࡲࢀࡓࡇ࡜ࢆཷ
ࡅ࡚ࠊ㠉᪂ⓗ་⸆ရࢆ┿࡟ᚲせ࡞ᝈ⪅࡟ᥦ౪ࡍࡿࡓࡵ࡟᭱㐺౑⏝᥎㐍࢞࢖ࢻ
ࣛ࢖ࣥࢆసᡂࡍࡿࡇ࡜࡜ࡋࡲࡋࡓࠋ
௒⯡ࠊࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧〇๣㸦㈍኎ྡ㸸࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ
PJ ཬࡧྠ PJ㸧ཬࡧ࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧〇๣㸦㈍኎ྡ㸸
࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ PJ ཬࡧྠ PJ㸧࡟ࡘ࠸࡚ࠊ㠀ᑠ⣽⬊⫵⒴ཪࡣᝏ
ᛶ㯮Ⰽ⭘࡟ᑐࡋ࡚౑⏝ࡍࡿ㝿ࡢ␃ព஦㡯 ࢆูῧ㸯㹼ูῧ㸲ࡢ࡜࠾ࡾ᭱㐺౑
⏝᥎㐍࢞࢖ࢻࣛ࢖ࣥ࡜ࡋ࡚ྲྀࡾࡲ࡜ࡵࡲࡋࡓࡢ࡛ࠊࡑࡢ౑⏝࡟ᙜࡓࡗ࡚ࡣࠊ
ᮏ࢞࢖ࢻࣛ࢖ࣥ࡟ࡘ࠸࡚␃ពࡉࢀࡿࡼ࠺ࠊ㈗⟶ෆࡢ་⒪ᶵ㛵ཬࡧ⸆ᒁ࡟ᑐࡍ
ࡿ࿘▱ࢆ࠾㢪࠸ࡋࡲࡍࠋ
29.2.14
28
1100
ูῧ㸯
᭱㐺౑⏝᥎㐍࢞࢖ࢻࣛ࢖ࣥ
ࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧
㸦㈍኎ྡ㸸࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 20 mgࠊ࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 100 mg㸧
㹼㠀ᑠ⣽⬊⫵⒴㹼
ᖹᡂ㸰㸷ᖺ㸰᭶
ཌ⏕ປാ┬
┠ḟ
1.
2.
3.
4.
5.
6.
ࡣࡌࡵ࡟
ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
⮫ᗋᡂ⦼
᪋タ࡟ࡘ࠸࡚
ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
P2
P3
P4
P10
P12
P14
1
㸬ࡣࡌࡵ࡟
་⸆ရࡢ᭷ຠᛶ࣭Ᏻ඲ᛶࡢ☜ಖࡢࡓࡵ࡟ࡣࠊῧ௜ᩥ᭩➼࡟ᇶ࡙࠸ࡓ㐺ṇ࡞౑⏝ࡀồࡵ
ࡽࢀࡿࠋࡉࡽ࡟ࠊ㏆ᖺࡢ⛉Ꮫᢏ⾡ࡢ㐍Ṍ࡟ࡼࡾࠊᢠయ་⸆ရ࡞࡝ࡢ㠉᪂ⓗ࡞᪂つస⏝ᶵ
ᗎ་⸆ရࡀᢎㄆࡉࢀࡿ୰࡛ࠊࡇࢀࡽࡢ་⸆ရࢆ┿࡟ᚲせ࡞ᝈ⪅࡟ᥦ౪ࡍࡿࡇ࡜ࡀႚ⥭ࡢ
ㄢ㢟࡜࡞ࡗ࡚࠾ࡾࠊ
⤒῭㈈ᨻ㐠Ⴀ࡜ᨵ㠉ࡢᇶᮏ᪉㔪 2016
㸦ᖹᡂ 28 ᖺ㸴᭶㸰᪥㛶㆟Ỵᐃ㸧
࡟࠾࠸࡚ࡶࠊ㠉᪂ⓗ་⸆ရ➼ࡢ౑⏝ࡢ᭱㐺໬᥎㐍ࢆᅗࡿࡇ࡜࡜ࡉࢀ࡚࠸ࡿࠋ
᪂つస⏝ᶵᗎ་⸆ရࡣࠊ⸆⌮స⏝ࡸᏳ඲ᛶࣉࣟࣇ࢓࢖ࣝࡀ᪤Ꮡࡢ་⸆ရ࡜᫂ࡽ࠿࡟␗
࡞ࡿࡇ࡜ࡀ࠶ࡿࠋࡇࡢࡓࡵࠊ᭷ຠᛶཬࡧᏳ඲ᛶ࡟㛵ࡍࡿ᝟ሗࡀ༑ศ⵳✚ࡍࡿࡲ࡛ࡢ㛫ࠊ
ᙜヱ་⸆ရࡢᜠᜨࢆᙉࡃཷࡅࡿࡇ࡜ࡀᮇᚅࡉࢀࡿᝈ⪅࡟ᑐࡋ࡚౑⏝ࡍࡿ࡜࡜ࡶ࡟ࠊ๪స
⏝ࡀⓎ⌧ࡋࡓ㝿࡟ᚲせ࡞ᑐᛂࢆ࡜ࡿࡇ࡜ࡀྍ⬟࡞୍ᐃࡢせ௳ࢆ‶ࡓࡍ་⒪ᶵ㛵࡛౑⏝
ࡍࡿࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ
ࡋࡓࡀࡗ࡚ࠊᮏ࢞࢖ࢻࣛ࢖࡛ࣥࡣࠊ㛤Ⓨẁ㝵ࡸࡇࢀࡲ࡛࡟ᚓࡽࢀ࡚࠸ࡿ་Ꮫ⸆Ꮫⓗ࣭
⛉Ꮫⓗぢᆅ࡟ᇶ࡙ࡁࠊ௨ୗࡢ་⸆ရࡢ᭱㐺࡞౑⏝ࢆ᥎㐍ࡍࡿほⅬ࠿ࡽᚲせ࡞せ௳ࠊ⪃࠼
᪉ཬࡧ␃ព஦㡯ࢆ♧ࡍࠋ
࡞࠾ࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ⊂❧⾜ᨻἲே་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓࠊබ┈♫ᅋἲே᪥ᮏ
⮫ᗋ⭘⒆Ꮫ఍ࠊ୍⯡♫ᅋἲே᪥ᮏ⮫ᗋෆ⛉་఍ࠊ≉ᐃ㠀Ⴀ฼άືἲே᪥ᮏ⫵⒴Ꮫ఍ཬࡧ
୍⯡♫ᅋἲே᪥ᮏ࿧྾ჾᏛ఍ࡢ༠ຊࡢࡶ࡜సᡂࡋࡓࠋ
ᑐ㇟࡜࡞ࡿ་⸆ရ㸸࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 20 mgࠊ࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 100 mg㸦୍⯡ྡ㸸
ࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧㸧
ᑐ㇟࡜࡞ࡿຠ⬟ཪࡣຠᯝ㸸ษ㝖୙⬟࡞㐍⾜࣭෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴
ᑐ㇟࡜࡞ࡿ⏝ἲཬࡧ⏝㔞㸸㏻ᖖࠊᡂே࡟ࡣࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧࡜ࡋ࡚ࠊ1 ᅇ 3mg/kg
㸦య㔜㸧ࢆ 2 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡍࡿࠋ
〇㐀㈍ ኎ ᴗ ⪅㸸ᑠ㔝⸆ရᕤᴗᰴᘧ఍♫
2
2㸬
㸬ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 20 mg㸭100 mg㸦୍⯡ྡ㸸ࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧ࠊ௨ୗࠕᮏ
๣ࠖ࡜࠸࠺ࠋ㸧ࡣࠊᑠ㔝⸆ရᕤᴗᰴᘧ఍♫࡜࣓ࢲࣞࢵࢡࢫ♫㸦⌧ࣈࣜࢫࢺ࣭࣐ࣝ࢖࣮ࣖ
ࢬ ࢫࢡ࢖ࣈ㸦BMS㸧♫㸧ࡀ㛤Ⓨࡋࡓࣄࢺ PD-1㸦Programmed cell death-1㸧࡟ᑐࡍࡿࣄࢺ
ᆺ IgG4 ࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡿࠋ
PD-1 ࡣࠊάᛶ໬ࡋࡓࣜࣥࣃ⌫㸦T ⣽⬊ࠊB ⣽⬊ཬࡧࢼࢳ࣮ࣗࣛࣝ࢟ࣛT ⣽⬊㸧ཬࡧ㦵
㧊⣔⣽⬊࡟Ⓨ⌧ࡍࡿ CD28 ࣇ࢓࣑࣮ࣜ㸦T ⣽⬊ࡢάᛶ໬ࢆ⿵ຓⓗ࡟ṇ࡜㈇࡟ไᚚࡍࡿศ
Ꮚ⩌㸧࡟ᒓࡍࡿཷᐜయ࡛࠶ࡿࠋPD-1 ࡣᢠཎᥦ♧⣽⬊࡟Ⓨ⌧ࡍࡿ PD-1 ࣜ࢞ࣥࢻ㸦PD-L1
ཬࡧ PD-L2㸧࡜⤖ྜࡋࠊࣜࣥࣃ⌫࡟ᢚไᛶࢩࢢࢼࣝࢆఏ㐩ࡋ࡚ࣜࣥࣃ⌫ࡢάᛶ໬≧ែࢆ
㈇࡟ㄪ⠇ࡋ࡚࠸ࡿࠋPD-1 ࣜ࢞ࣥࢻࡣᢠཎᥦ♧⣽⬊௨እ࡟ࣄࢺࡢᵝࠎ࡞⭘⒆⤌⧊࡟Ⓨ⌧
ࡋ࡚࠾ࡾࠊᝏᛶ㯮Ⰽ⭘ᝈ⪅࠿ࡽษ㝖ࡋࡓ⭘⒆⤌⧊࡟࠾ࡅࡿ PD-L1 ࡢⓎ⌧࡜⾡ᚋࡢ⏕Ꮡ
ᮇ㛫࡜ࡢ㛫࡟㈇ࡢ┦㛵㛵ಀࡀ࠶ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ㸦Cancer 2010; 116: 1757-66㸧
ࠋ
ࡲࡓࠊᝏᛶ㯮Ⰽ⭘ᝈ⪅࡛ࡣ⤌⧊ᾐ₶ T ⣽⬊ࡀ⏘⏕ࡍࡿ࢖ࣥࢱ࣮ࣇ࢙࣐ࣟࣥ࢞ࣥ㸦IFN-γ㸧
࡟ࡼࡗ࡚ PD-L1 ࡢⓎ⌧ࡀㄏᑟࡉࢀࠊ㌿⛣ࡋࡓ⭘⒆⤌⧊࡟࠾ࡅࡿ PD-L1 ࡢⓎ⌧࡜⾡ᚋࡢ
⏕Ꮡᮇ㛫࡜ࡢ㛫࡟ṇࡢ┦㛵㛵ಀࡀ࠶ࡿ࡜ࡢሗ࿌ࡶ࠶ࡿ 㸦Sci Transl Med 2012: 28:
127ra37㸧ࠋࡉࡽ࡟ࠊPD-L1 ࢆᙉไⓎ⌧ࡉࡏࡓࡀࢇ⣽⬊ࡣࠊᢠཎ≉␗ⓗ CD8 㝧ᛶ T ⣽⬊
ࡢ⣽⬊യᐖάᛶࢆῶᙅࡉࡏࡿࡀࠊᢠ PD-L1 ᢠయ࡛ PD-1 ࡜ PD-L1 ࡜ࡢ⤖ྜࢆ㜼ᐖࡍࡿ࡜
ࡑࡢ⣽⬊യᐖάᛶࡀᅇ᚟ࡍࡿࡇ࡜ࡀ♧ࡉࢀ࡚࠸ࡿࠊ➼ࡢࡇ࡜࠿ࡽ PD-1/PD-1 ࣜ࢞ࣥࢻ⤒
㊰ࡣࠊࡀࢇ⣽⬊ࡀᢠཎ≉␗ⓗ࡞ T ⣽⬊࠿ࡽࡢᨷᧁ➼ࢆᅇ㑊ࡍࡿᶵᗎࡢ୍ࡘ࡜ࡋ࡚⪃࠼ࡽ
ࢀ࡚࠸ࡿࠋ
ᮏ๣ࡣࠊ⸆⌮ヨ㦂ࡢ⤖ᯝ࠿ࡽ PD-1 ࡢ⣽⬊እ㡿ᇦ㸦PD-1 ࣜ࢞ࣥࢻ⤖ྜ㡿ᇦ㸧࡟⤖ྜࡋࠊ
PD-1 ࡜ PD-1 ࣜ࢞ࣥࢻ࡜ࡢ⤖ྜࢆ㜼ᐖࡍࡿࡇ࡜࡟ࡼࡾࠊࡀࢇᢠཎ≉␗ⓗ࡞ T ⣽⬊ࡢάᛶ
໬ཬࡧࡀࢇ⣽⬊࡟ᑐࡍࡿ⣽⬊യᐖάᛶࢆቑᙉࡍࡿࡇ࡜࡛ᣢ⥆ⓗ࡞ᢠ⭘⒆ຠᯝࢆ♧ࡍࡇ
࡜ࡀ☜ㄆࡉࢀ࡚࠸ࡿࠋ
ࡇࢀࡽࡢ▱ぢ࠿ࡽࠊᮏ๣ࡣᝏᛶ⭘⒆࡟ᑐࡍࡿ᪂ࡓ࡞἞⒪⸆࡟࡞ࡾᚓࡿࡶࡢ࡜ᮇᚅࡉࢀࠊ
㠀ᑠ⣽⬊⫵⒴ᝈ⪅ࢆᑐ㇟࡜ࡋࡓ⮫ᗋヨ㦂ࢆᐇ᪋ࡋࠊ᭷ຠᛶࠊᏳ඲ᛶཬࡧᚸᐜᛶࡀ☜ㄆࡉ
ࢀࡓࠋ
ᮏ๣ࡢస⏝ᶵᗎ࡟ᇶ࡙ࡃ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝➼ࡀ࠶ࡽࢃࢀࠊ㔜⠜ཪࡣṚஸ࡟
⮳ࡿྍ⬟ᛶࡀ࠶ࡿࠋᮏ๣ࡢᢞ୚୰ཬࡧᢞ୚ᚋ࡟ࡣࠊᝈ⪅ࡢほᐹࢆ༑ศ࡟⾜࠸ࠊ␗ᖖࡀㄆ
ࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺
ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝ
ࣔࣥ๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ᚲせࡀ࠶ࡿࠋ
3
3㸬
㸬⮫ᗋᡂ⦼
ษ㝖୙⬟࡞㐍⾜࣭෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴㸦ᡥᖹୖ⓶⒴ཬࡧ㠀ᡥᖹୖ⓶⒴㸧ࡢᢎㄆ᫬࡟ホ౯
ࢆ⾜ࡗࡓ୺࡞⮫ᗋヨ㦂ࡢᡂ⦼ࢆ♧ࡍࠋ
࠙᭷ຠᛶࠚ
ࠑᡥᖹୖ⓶⒴ࠒ
ձᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-05 ヨ㦂㸧
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿษ㝖୙⬟࡞ϪB ᮇϫᮇཪࡣ෌Ⓨࡢᡥᖹୖ⓶⒴
ᝈ⪅㸦ECOG Performance Status 0 ཬࡧ 1㸧35 ౛ࢆᑐ㇟࡟ࠊᮏ๣ 3 mg/kg ࢆ 2 㐌㛫㛫㝸࡛
Ⅼ⁲㟼ὀࡋࡓࠋ୺せホ౯㡯┠࡛࠶ࡿዌຠ⋡㸦RECIST ࢞࢖ࢻࣛ࢖ࣥ 1.1 ∧࡟ᇶ࡙ࡃ୰ኸ
ุᐃ࡟ࡼࡿ CR ཪࡣ PR㸧ࡣ 25.7%㸦95%ಙ㢗༊㛫㸸14.2㹼42.1%㸧࡛࠶ࡗࡓࠋ࡞࠾ࠊ஦
๓࡟タᐃࡋࡓ㜈್ࡣ 9.0%࡛࠶ࡗࡓࠋ
ղᾏእ➨Ϫ┦ヨ㦂㸦CA209017 ヨ㦂㸧㸦N Engl J Med 2015; 373: 123-35㸧
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿษ㝖୙⬟࡞ϪB ᮇϫᮇཪࡣ෌Ⓨࡢᡥᖹୖ⓶⒴
ᝈ⪅㸦ECOG Performance Status 0 ཬࡧ 1㸧272 ౛㸦ᮏ๣⩌ 135 ౛ࠊࢻࢭࢱ࢟ࢭࣝ⩌ 137
౛㸧ࢆᑐ㇟࡟ࠊࢻࢭࢱ࢟ࢭࣝࢆᑐ↷࡜ࡋ࡚ᮏ๣ 3 mg/kg ࢆ 2 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡋࡓࠋ
୺せホ౯㡯┠࡛࠶ࡿ඲⏕Ꮡᮇ㛫㸦୰ኸ್㹙95%ಙ㢗༊㛫㹛
㸧ࡣࠊᮏ๣⩌࡛ 9.23㹙7.33㹼13.27㹛
࢝᭶ࠊࢻࢭࢱ࢟ࢭࣝ⩌࡛ 6.01㹙5.13㹼7.33㹛࢝᭶࡛࠶ࡾࠊᮏ๣ࡣࢻࢭࢱ࢟ࢭࣝ࡟ᑐࡋ⤫
ィᏛⓗ࡟᭷ព࡞ᘏ㛗ࢆ♧ࡋࡓ㸦ࣁࢨ࣮ࢻẚ 0.59㹙96.85%ಙ㢗༊㛫㸸0.43㹼0.81㹛ࠊp=0.0002
㹙ᒙู log-rank ᳨ᐃ㹛
㸧
ࠋ
OS ࡢ୰㛫ゎᯒࡢ Kaplan-Meier ᭤⥺㸦↓సⅭ໬ࡉࢀࡓ㞟ᅋ㸧
4
ࠑ㠀ᡥᖹୖ⓶⒴ࠒ
ձᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-06 ヨ㦂㸧
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿษ㝖୙⬟࡞ϪB ᮇϫᮇཪࡣ෌Ⓨࡢ㠀ᡥᖹୖ⓶
⒴ᝈ⪅㸦ECOG Performance Status 0 ཬࡧ 1㸧76 ౛ࢆᑐ㇟࡟ࠊᮏ๣ 3 mg/kg ࢆ 2 㐌㛫㛫㝸
࡛Ⅼ⁲㟼ὀࡋࡓࠋ୺せホ౯㡯┠࡛࠶ࡿዌຠ⋡㸦RECIST ࢞࢖ࢻࣛ࢖ࣥ 1.1 ∧࡟ᇶ࡙ࡃ୰
ኸุᐃ࡟ࡼࡿ CR ཪࡣ PR㸧ࡣ 19.7%㸦95%ಙ㢗༊㛫㸸12.3㹼30.0%㸧࡛࠶ࡗࡓࠋ࡞࠾ࠊ
஦๓࡟タᐃࡋࡓ㜈್ࡣ 9.0%࡛࠶ࡗࡓࠋ
ղᾏእ➨Ϫ┦ヨ㦂㸦CA209057 ヨ㦂㸧㸦N Engl J Med 2015; 373: 1627-39㸧
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿษ㝖୙⬟࡞ϪB ᮇϫᮇཪࡣ෌Ⓨࡢ㠀ᡥᖹୖ⓶
⒴ᝈ⪅㸦ECOG Performance Status 0 ཬࡧ 1㸧582 ౛㸦ᮏ๣⩌ 292 ౛ࠊࢻࢭࢱ࢟ࢭࣝ⩌ 290
౛㸧ࢆᑐ㇟࡟ࠊࢻࢭࢱ࢟ࢭࣝࢆᑐ↷࡜ࡋ࡚ᮏ๣ 3 mg/kg ࢆ 2 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡋࡓࠋ
୺せホ౯㡯┠࡛࠶ࡿ඲⏕Ꮡᮇ㛫㸦୰ኸ್㹙95%ಙ㢗༊㛫㹛㸧ࡣࠊᮏ๣⩌࡛ 12.19㹙9.66㹼
14.98㹛࢝᭶ࠊࢻࢭࢱ࢟ࢭࣝ⩌࡛ 9.36㹙8.05㹼10.68㹛࢝᭶࡛࠶ࡾࠊᮏ๣ࡣࢻࢭࢱ࢟ࢭࣝ
࡟ᑐࡋ⤫ィᏛⓗ࡟᭷ព࡞ᘏ㛗ࢆ♧ࡋࡓ㸦ࣁࢨ࣮ࢻẚ 0.73㹙95.92%ಙ㢗༊㛫㸸0.59㹼0.89㹛
ࠊ
p=0.0015㹙ᒙู log-rank ᳨ᐃ㹛
㸧
ࠋ
OSࡢ୰㛫ゎᯒࡢKaplan-Meier᭤⥺㸦↓సⅭ໬ࡉࢀࡓ㞟ᅋ㸧
5
㸦ཧ⪃᝟ሗ㸧
PD-L1Ⓨ⌧≧ἣูࡢ᭷ຠᛶཬࡧᏳ඲ᛶ
ᾏእ➨Ϫ┦ヨ㦂㸦CA209017ヨ㦂ཬࡧCA209057ヨ㦂㸧࡟⤌ࡳධࢀࡽࢀࡓᝈ⪅ࡢ࠺ࡕࠊ⭘
⒆⤌⧊࡟࠾࠸࡚PD-L1ࢆⓎ⌧ࡋࡓ⭘⒆⣽⬊ࡀ༨ࡵࡿ๭ྜ㸦௨ୗࠕPD-L1Ⓨ⌧⋡ࠖ࡜࠸࠺ࠋ
㸧
࡟㛵ࡍࡿ᝟ሗࡀᚓࡽࢀࡓ୍㒊ࡢᝈ⪅ࡢࢹ࣮ࢱ࡟ᇶ࡙ࡁࠊPD-L1Ⓨ⌧⋡ู࡟᥈⣴ⓗ࡟ゎᯒ
ࢆ⾜ࡗࡓ᭷ຠᛶཬࡧᏳ඲ᛶࡢ⤖ᯝࡣ௨ୗࡢ࡜࠾ࡾ࡛࠶ࡗࡓࠋ
᭷ຠᛶ࡟㛵ࡋ࡚ࡣࠊᡥᖹୖ⓶⒴࡛ࡣࠊPD-L1ࡢⓎ⌧⋡࡟ࡼࡽࡎࠊࢻࢭࢱ࢟ࢭࣝ⩌࡜ẚ㍑
ࡋ࡚ᮏ๣⩌࡛OSࡀᘏ㛗ࡍࡿഴྥࡀㄆࡵࡽࢀࡓࠋ
㠀ᡥᖹୖ⓶⒴࡛ࡣࠊPD-L1Ⓨ⌧⋡ࡀ1%ᮍ‶ࡢሙྜ࡟ࢻࢭࢱ࢟ࢭࣝ⩌࡜࡯ࡰྠᵝࡢ⤖ᯝ࡛
࠶ࡗࡓ㸦ୗᅗ㸧
ࠋ
࡞࠾ࠊᡥᖹୖ⓶⒴ࠊ㠀ᡥᖹୖ⓶⒴࡜ࡶ࡟ࠊPD-L1ࡢⓎ⌧⋡࡟ࡼࡽࡎࠊᮏ๣ࡢᏳ඲ᛶࣉࣟ
ࣇ࢓࢖ࣝࡣྠᵝ࡛࠶ࡗࡓࠋ
CA209057 ヨ㦂ࡢ PD-L1 Ⓨ⌧⋡ู࡛ࡢ OS ࡢ୰㛫ゎᯒࡢ Kaplan-Meier ᭤⥺
㸦ᕥᅗ㸸PD-L1㸺1%ࡢᝈ⪅㞟ᅋࠊྑᅗ㸸PD-L1Ӎ1%ࡢᝈ⪅㞟ᅋ㸧
6
࠙Ᏻ඲ᛶࠚ
ࠑᡥᖹୖ⓶⒴ࠒ
ձᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-05ヨ㦂㸧
Ⓨ⌧⋡ࡀ5%௨ୖࡢ๪స⏝
Grade
඲ Grade
๪స⏝㡯┠
Ⓨ⌧ Ⓨ⌧⋡
㸦MedDRA ࡟ࡼࡿ SOC㺃PT ศ㢮㸧
⪅ᩘ
㸦㸣㸧
35
ᑐ㇟⪅ᩘ㻌㻌
24
( 68.6)
඲య㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
⾑ᾮ䛚䜘䜃䝸䞁䝟⣔㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
㈋⾑㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
4
( 11.4)
ෆศἪ㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
⮬ᕫච␿ᛶ⏥≧⭢⅖㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
5
( 14.3)
⫶⭠㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
ୗ⑩㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
3
( 8.6)
ᝏᚰ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
11
( 31.4)
୍⯡䞉඲㌟㞀ᐖ䛚䜘䜃ᢞ୚㒊఩䛾≧ែ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
5
( 14.3)
೏ᛰឤ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
ᮎᲈᛶᾋ⭘㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
5
( 14.3)
Ⓨ⇕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
ච␿⣔㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
㐣ᩄ⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
8
( 22.9)
⮫ᗋ᳨ᰝ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
䜰䝇䝟䝷䜼䞁㓟䜰䝭䝜䝖䝷䞁䝇䝣䜵䝷䞊䝊ቑຍ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
⾑୰䜽䝺䜰䝏䞁䝩䝇䝩䜻䝘䞊䝊ቑຍ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
3
( 8.6)
䝸䞁䝟⌫ᩘῶᑡ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
7
( 20.0)
௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
ప䜰䝹䝤䝭䞁⾑⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
5
( 14.3)
㣗ḧῶ㏥㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
➽㦵᱁⣔䛚䜘䜃⤖ྜ⤌⧊㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
㛵⠇③㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
3
( 8.6)
⚄⤒⣔㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
ᮎᲈᛶឤぬ䝙䝳䞊䝻䝟䝏䞊㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
5
( 14.3)
࿧྾ჾ䚸⬚㒌䛚䜘䜃⦪㝸㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
⫵ฟ⾑㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
10
( 28.6)
⓶⭵䛚䜘䜃⓶ୗ⤌⧊㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
䛦⒔ᵝ⓶⭵⅖㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
⣚ᩬ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
5
( 14.3)
Ⓨ⑈㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
2
( 5.7)
ᩬ≧ୣ⑈≧⓶⑈㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
Grade 3-4
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
35
2
( 5.7)
2
( 5.7)
2
( 5.7)
Grade 5
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
35
0
(0.0)
་ᖌ࠿ࡽሗ࿌ࡉࢀࡓ᭷ᐖ஦㇟ྡࡣ㸪MedDRA ver 17.1Jࢆ⏝࠸࡚ㄞࡳ᭰࠼ࡓ㸬
GradeࡣCTCAE㸦Common Terminology Criteria for Adverse Events㸧 v4᪥ᮏㄒヂJCOG∧࡟‽ࡌࡿࠋ
࡞࠾ࠊ㛫㉁ᛶ⫵⑌ᝈ 2 ౛㸦5.7%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 2 ౛㸦5.7%㸧ࠊ⚄⤒㞀ᐖ㸦ࢠ
࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧3 ౛㸦8.6%㸧ࠊ⫢ᶵ⬟㞀ᐖࡣ 2 ౛㸦5.7%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖࡣ
3 ౛㸦8.6%㸧ࠊ๪⭈ᶵ⬟㞀ᐖ 1 ౛㸦2.9%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧ࡣ 1 ౛
㸦2.9%㸧ཬࡧ infusion reaction ࡣ 2 ౛㸦5.7%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶
⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࠊୗᆶయᶵ⬟㞀ᐖࠊ1 ᆺ⢾ᒀ⑓ࠊ⮅⅖ࠊ㔜⑕
➽↓ຊ⑕ࠊ⬻⅖࣭㧊⭷⅖ࠊࡪ࡝࠺⭷⅖ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
7
ղᾏእ➨Ϫ┦ヨ㦂㸦CA209017ヨ㦂㸧㸦N Engl J Med 2015; 373: 123-35㸧
Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝
Grade
඲ Grade㻌
๪స⏝㡯┠
Ⓨ⌧ Ⓨ⌧⋡
㸦MedDRA ࡟ࡼࡿ SOC㺃PT ศ㢮㸧
⪅ᩘ
㸦㸣㸧
131
ᑐ㇟⪅ᩘ㻌㻌
76
( 58.0)
඲య㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 18.3)
⫶⭠㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 24
10
( 7.6)
ୗ⑩㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
12
( 9.2)
ᝏᚰ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
41
( 31.3)
୍⯡䞉඲㌟㞀ᐖ䛚䜘䜃ᢞ୚㒊఩䛾≧ែ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
13
( 9.9)
↓ຊ⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
21
( 16.0)
⑂ປ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 13.7)
௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 18
( 10.7)
㣗ḧῶ㏥㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 14
17
( 13.0)
➽㦵᱁⣔䛚䜘䜃⤖ྜ⤌⧊㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
7
( 5.3)
㛵⠇③㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
Grade 3-4㻌
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
131
9
( 6.9)
1
( 0.8)
1
( 0.8)
1
1
1
( 0.8)
( 0.8)
( 0.8)
Grade 5㻌
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
131
0
(0.0)
་ᖌ࠿ࡽሗ࿌ࡉࢀࡓ᭷ᐖ஦㇟ྡࡣ㸪MedDRA ver 17.1Jࢆ⏝࠸࡚ㄞࡳ᭰࠼ࡓ㸬
GradeࡣCTCAE㸦Common Terminology Criteria for Adverse Events㸧 v4࡟‽ࡌࡿࠋ
࡞࠾ࠊ㛫㉁ᛶ⫵⑌ᝈ 6 ౛㸦4.6%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 11 ౛㸦8.4%㸧ࠊ⚄⤒㞀ᐖ㸦ࢠ
࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧13 ౛㸦9.9%㸧ࠊ⫢ᶵ⬟㞀ᐖࡣ 4 ౛㸦3.1%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ
ࡣ 5 ౛㸦3.8%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧ࡣ 4 ౛㸦3.1%㸧ࠊ㔜⑕➽↓ຊ⑕ 1
౛㸦0.8%㸧ࠊཬࡧ infusion reaction ࡣ 1 ౛㸦0.8%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ㔜ᗘࡢ⓶⭵㞀
ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࠊୗᆶయᶵ⬟㞀ᐖࠊ๪⭈ᶵ⬟㞀ᐖࠊ1
ᆺ⢾ᒀ⑓ࠊ⮅⅖ࠊ⬻⅖࣭㧊⭷⅖ࠊࡪ࡝࠺⭷⅖ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
ࠑ㠀ᡥᖹୖ⓶⒴ࠒ
ձᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-06ヨ㦂㸧
Ⓨ⌧⋡ࡀ5%௨ୖࡢ๪స⏝
Grade
඲ Grade㻌
๪స⏝㡯┠
Ⓨ⌧ Ⓨ⌧⋡
㸦MedDRA ࡟ࡼࡿ SOC㺃PT ศ㢮㸧
⪅ᩘ
㸦㸣㸧
76
ᑐ㇟⪅ᩘ㻌㻌
64
( 84.2)
඲య㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
9
( 11.8)
ෆศἪ㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
7
( 9.2)
⏥≧⭢ᶵ⬟పୗ⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 34.2)
⫶⭠㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 26
5
( 6.6)
౽⛎㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
4
( 5.3)
ୗ⑩㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
8
( 10.5)
ᝏᚰ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
4
( 5.3)
ཱྀෆ⅖㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
4
( 5.3)
჎ྤ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
29
( 38.2)
୍⯡䞉඲㌟㞀ᐖ䛚䜘䜃ᢞ୚㒊఩䛾≧ែ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
9
( 11.8)
⑂ປ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
11
( 14.5)
೏ᛰឤ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
11
( 14.5)
Ⓨ⇕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 23.7)
⮫ᗋ᳨ᰝ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 18
6
( 7.9)
䝸䞁䝟⌫ᩘῶᑡ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 22.4)
௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 17
4
( 5.3)
ప䝘䝖䝸䜴䝮⾑⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 14.5)
㣗ḧῶ㏥㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 11
( 13.2)
⚄⤒⣔㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 10
4
( 5.3)
ᾋືᛶ䜑䜎䛔㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 15.8)
࿧྾ჾ䚸⬚㒌䛚䜘䜃⦪㝸㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 12
8
Grade 3-4
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
76
16
( 21.1)
2
( 2.6)
1
1
( 1.3)
( 1.3)
3
2
3
2
1
1
1
4
(
(
(
(
(
(
(
(
3.9)
2.6)
3.9)
2.6)
1.3)
1.3)
1.3)
5.3)
Grade 5㻌
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
76
0
(0.0)
㛫㉁ᛶ⫵⑌ᝈ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
⓶⭵䛚䜘䜃⓶ୗ⤌⧊㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
䛭䛖⑛⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
Ⓨ⑈㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
ᩬ≧ୣ⑈≧⓶⑈㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
4
26
6
11
4
( 5.3)
( 34.2)
( 7.9)
( 14.5)
( 5.3)
2
1
1
( 2.6)
( 1.3)
( 1.3)
་ᖌ࠿ࡽሗ࿌ࡉࢀࡓ᭷ᐖ஦㇟ྡࡣ㸪MedDRA ver 17.0Jࢆ⏝࠸࡚ㄞࡳ᭰࠼ࡓ㸬
GradeࡣCTCAE㸦Common Terminology Criteria for Adverse Events㸧 v4᪥ᮏㄒヂJCOG∧࡟‽ࡌࡿࠋ
࡞࠾ࠊ㛫㉁ᛶ⫵⑌ᝈ4౛㸦5.3%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩5౛㸦6.6%㸧ࠊ⚄⤒㞀ᐖ㸦ࢠࣛ
࣭ࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧10౛㸦13.2%㸧ࠊ⫢ᶵ⬟㞀ᐖࡣ5౛㸦6.6%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖࡣ
10౛㸦13.2%㸧ࠊ๪⭈ᶵ⬟㞀ᐖ1౛㸦1.3%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧ࡣ4౛
㸦5.3%㸧ཬࡧinfusion reactionࡣ3౛㸦3.9%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶
⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࠊୗᆶయᶵ⬟㞀ᐖࠊ1ᆺ⢾ᒀ⑓ࠊ⮅⅖ࠊ㔜⑕
➽↓ຊ⑕ࠊ⬻⅖࣭㧊⭷⅖ࠊࡪ࡝࠺⭷⅖ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
ղᾏእ➨Ϫ┦ヨ㦂㸦CA209057 ヨ㦂㸧㸦N Engl J Med 2015; 373: 1627-39㸧
Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝
Grade
඲ Grade㻌
๪స⏝㡯┠
Ⓨ⌧ Ⓨ⌧⋡
㸦MedDRA ࡟ࡼࡿ SOC㺃PT ศ㢮㸧
⪅ᩘ
㸦㸣㸧
287
ᑐ㇟⪅ᩘ㻌㻌
( 69.3)
඲య㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 199
( 8.4)
ෆศἪ㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 24
19
( 6.6)
⏥≧⭢ᶵ⬟పୗ⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 25.8)
⫶⭠㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 74
22
( 7.7)
ୗ⑩㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
34
( 11.8)
ᝏᚰ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
15
( 5.2)
჎ྤ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
90
( 31.4)
୍⯡䞉඲㌟㞀ᐖ䛚䜘䜃ᢞ୚㒊఩䛾≧ែ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
29
( 10.1)
↓ຊ⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
46
( 16.0)
⑂ປ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 15.0)
௦ㅰ䛚䜘䜃ᰤ㣴㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 43
( 10.5)
㣗ḧῶ㏥㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 30
36
( 12.5)
➽㦵᱁⣔䛚䜘䜃⤖ྜ⤌⧊㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
16
( 5.6)
㛵⠇③㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
60
( 20.9)
⓶⭵䛚䜘䜃⓶ୗ⤌⧊㞀ᐖ㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
( 8.4)
䛭䛖⑛⑕㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌 24
27
( 9.4)
Ⓨ⑈㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌㻌
Grade 3-4㻌
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
287
30
( 10.5)
4
2
2
( 1.4)
( 0.7)
( 0.7)
4
1
3
2
(
(
(
(
3
( 1.0)
3
( 1.0)
1
( 0.3)
Grade 5㻌
Ⓨ⌧ Ⓨ⌧⋡
⪅ᩘ
㸦㸣㸧
287
0
(0.0)
1.4)
0.3)
1.0)
0.7)
་ᖌ࠿ࡽሗ࿌ࡉࢀࡓ᭷ᐖ஦㇟ྡࡣ㸪MedDRA ver 17.1Jࢆ⏝࠸࡚ㄞࡳ᭰࠼ࡓ㸬
GradeࡣCTCAE㸦Common Terminology Criteria for Adverse Events㸧 v4࡟‽ࡌࡿࠋ
࡞࠾ࠊ㛫㉁ᛶ⫵⑌ᝈ 10 ౛㸦3.5%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 22 ౛㸦7.7%㸧ࠊ⚄⤒㞀ᐖ㸦ࢠ
࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧26 ౛㸦9.1%㸧ࠊ⫢ᶵ⬟㞀ᐖࡣ 15 ౛㸦5.2%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ
ࡣ 27 ౛㸦9.4%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧ࡣ 7 ౛㸦2.4%㸧ࠊ⬻⅖࣭㧊⭷⅖
1 ౛㸦0.3%㸧ཬࡧ infusion reaction ࡣ 8 ౛㸦2.8%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ㔜ᗘࡢ⓶⭵㞀
ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࠊୗᆶయᶵ⬟㞀ᐖࠊ๪⭈ᶵ⬟㞀ᐖࠊ1
ᆺ⢾ᒀ⑓ࠊ⮅⅖ࠊ㔜⑕➽↓ຊ⑕ࠊࡪ࡝࠺⭷⅖ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
9
4㸬
㸬᪋タ࡟ࡘ࠸࡚
ᢎㄆ᮲௳࡜ࡋ࡚౑⏝ᡂ⦼ㄪᰝ㸦඲౛ㄪᰝ㸧ࡀㄢࡏࡽࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᙜヱㄪᰝࢆ㐺ษ
࡟ᐇ᪋࡛ࡁࡿ᪋タ࡛࠶ࡿᚲせࡀ࠶ࡿࠋࡑࡢୖ࡛ࠊᮏ๣ࡢᢞ୚ࡀ㐺ษ࡞ᝈ⪅ࢆデ᩿࣭≉ᐃ
ࡋࠊᮏ๣ࡢᢞ୚࡟ࡼࡾ㔜⠜࡞๪స⏝ࢆⓎ⌧ࡋࡓ㝿࡟ᑐᛂࡍࡿࡇ࡜ࡀᚲせ࡞ࡓࡵࠊ௨ୗࡢ
ձ㹼ճࡢࡍ࡭࡚ࢆ‶ࡓࡍ᪋タ࡟࠾࠸࡚౑⏝ࡍࡿ࡭ࡁ࡛࠶ࡿࠋ
ձ ᪋タ࡟ࡘ࠸࡚
ձ-1 ୗグࡢ㸦1㸧㹼㸦5㸧ࡢ࠸ࡎࢀ࠿࡟ヱᙜ䛩䜛᪋タ䛷䛒䜛䛣䛸䚹
(1) ཌ⏕ປാ኱⮧ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔➼㸦㒔㐨ᗓ┴ࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊ
ᆅᇦࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊᆅᇦࡀࢇデ⒪⑓㝔࡞࡝㸧㸦ᖹᡂ 28 ᖺ 10 ᭶ 1 ᪥᫬Ⅼ㸸
427 ᪋タ㸧
(2) ≉ᐃᶵ⬟⑓㝔㸦ᖹᡂ 28 ᖺ 9 ᭶ 1 ᪥᫬Ⅼ㸸84 ᪋タ㸧
(3) 㒔㐨ᗓ┴▱஦ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠ⑓㝔㸦ࡀࢇデ⒪㐃ᦠᣦᐃ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ
༠ຊ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ᥎㐍⑓㝔࡞࡝㸧
(4) እ᮶໬Ꮫ⒪ἲᐊࢆタ⨨ࡋࠊእ᮶໬Ꮫ⒪ἲຍ⟬ 1 ཪࡣእ᮶໬Ꮫ⒪ἲຍ⟬ 2 ࡢ᪋タᇶ‽
࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7 ᭶ 1 ᪥᫬Ⅼ㸸 2538 ᪋タ㸧
(5) ᢠᝏᛶ⭘⒆๣ฎ᪉⟶⌮ຍ⟬ࡢ᪋タᇶ‽࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7
᭶ 1 ᪥᫬Ⅼ㸸1284 ᪋タ㸧
ձ-2 ⫵⒴ࡢ໬Ꮫ⒪ἲཬࡧ๪స⏝Ⓨ⌧᫬ࡢᑐᛂ࡟༑ศ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ㸦ୗ⾲ࡢ
࠸ࡎࢀ࠿࡟ヱᙜࡍࡿ་ᖌ㸧ࡀࠊᙜヱデ⒪⛉ࡢᮏ๣࡟㛵ࡍࡿ἞⒪ࡢ㈐௵⪅࡜ࡋ࡚㓄⨨ࡉࢀ
࡚࠸ࡿࡇ࡜ࠋ
⾲
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 5 ᖺ௨ୖࡢࡀࢇ἞⒪ࡢ⮫ᗋ◊ಟࢆ⾜
ࡗ࡚࠸ࡿࡇ࡜ࠋ࠺ࡕࠊ2 ᖺ௨ୖࡣࠊࡀࢇ⸆≀⒪ἲࢆ୺࡜ࡋࡓ⮫ᗋ⭘⒆Ꮫࡢ◊ಟࢆ⾜
࡞ࡗ࡚࠸ࡿࡇ࡜ࠋ
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 4 ᖺ௨ୖࡢ⮫ᗋ⤒㦂ࢆ᭷ࡋ࡚࠸ࡿࡇ
࡜ࠋ࠺ࡕࠊ3 ᖺ௨ୖࡣࠊ⫵⒴ࡢࡀࢇ⸆≀⒪ἲࢆྵࡴ࿧྾ჾ⑓Ꮫࡢ⮫ᗋ◊ಟࢆ⾜ࡗ࡚
࠸ࡿࡇ࡜ࠋ
ղ 㝔ෆࡢ་⸆ရ᝟ሗ⟶⌮ࡢయไ࡟ࡘ࠸࡚
་⸆ရ᝟ሗ⟶⌮࡟ᚑ஦ࡍࡿᑓ௵⪅ࡀ㓄⨨ࡉࢀࠊ〇⸆௻ᴗ࠿ࡽࡢ᝟ሗ❆ཱྀࠊ᭷ຠᛶ࣭Ᏻ඲
ᛶ➼⸆Ꮫⓗ᝟ሗࡢ⟶⌮ཬࡧ་ᖌ➼࡟ᑐࡍࡿ᝟ሗᥦ౪ࠊ᭷ᐖ஦㇟ࡀⓎ⏕ࡋࡓሙྜࡢሗ࿌ᴗ
ົࠊ➼ࡀ㏿ࡸ࠿࡟⾜ࢃࢀࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
10
ճ ๪స⏝࡬ࡢᑐᛂ࡟ࡘ࠸࡚
䐡-1 ᪋タయไ࡟㛵ࡍࡿせ௳
㛫㉁ᛶ⫵⑌ᝈ➼ࡢ㔜⠜࡞๪స⏝ࡀⓎ⏕ࡋࡓ㝿࡟ࠊ24 ᫬㛫デ⒪యไࡢୗࠊᙜヱ᪋タཪࡣ
㐃ᦠ᪋タ࡟࠾࠸࡚ࠊⓎ⌧ࡋࡓ๪స⏝࡟ᛂࡌ࡚ධ㝔⟶⌮ཬࡧ CT ➼ࡢ๪స⏝ࡢ㚷ู࡟ᚲせ
࡞᳨ᰝࡢ⤖ᯝࡀᙜ᪥୰࡟ᚓࡽࢀࠊ┤ࡕ࡟ᑐᛂྍ⬟࡞యไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
㻌
䐡-2 ་⒪ᚑ஦⪅࡟ࡼࡿ᭷ᐖ஦㇟ᑐᛂ࡟㛵ࡍࡿせ௳
ࡀࢇデ⒪࡟ᦠࢃࡿᑓ㛛ⓗ࡞▱㆑ཬࡧᢏ⬟ࢆ᭷ࡍࡿ་⒪ᚑ஦⪅ࡀ๪స⏝ࣔࢽࢱࣜࣥࢢࢆ
ྵࡵࡓⱞ③ࡢࢫࢡ࣮ࣜࢽࣥࢢࢆ⾜࠸୺἞་࡜᝟ሗࢆඹ᭷࡛ࡁࡿࢳ࣮࣒་⒪యไࡀᩚഛ
ࡉࢀ࡚࠸ࡿࡇ࡜ࠋ࡞࠾ࠊᩚഛయไ࡟ࡘ࠸࡚ࠊࡀࢇᝈ⪅࡜ࡑࡢᐙ᪘࡟༑ศ࡟࿘▱ࡉࢀ࡚࠸
ࡿࡇ࡜ࠋ
㻌
䐡-3 ๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚
๪స⏝㸦㛫㉁ᛶ⫵⑌ᝈ࡟ຍ࠼ࠊ㔜⑕➽↓ຊ⑕ࠊᚰ➽⅖ࠊ➽⅖ࠊᶓ⣠➽⼥ゎ⑕ࠊ኱⭠⅖ࠊ
㔜ᗘࡢୗ⑩ࠊ1 ᆺ⢾ᒀ⑓ࠊ⫢ᶵ⬟㞀ᐖࠊ⏥≧⭢ᶵ⬟㞀ᐖࠊ⚄⤒㞀ᐖࠊ⭈㞀ᐖ㸦⭈୙඲࣭
ᒀ⣽⟶㛫㉁ᛶ⭈⅖ࢆྵࡴ㸧
ࠊ๪⭈㞀ᐖࠊ⬻⅖ࠊ㔜ᗘࡢ⓶⭵㞀ᐖࠊ㟼⬦⾑ᰦሰᰦ⑕ࠊinfusion
reactionࠊච␿ᛶ⾑ᑠᯈῶᑡᛶ⣸ᩬ⑓㸦ITP㸧㐣ᗘࡢච␿཯ᛂࠊ⬇⫾ඣẘᛶࠊᚰ⮚㞀ᐖ㸦ᚰ
ᡣ⣽ື࣭ᚎ⬦࣭ᚰᐊᛶᮇእ཰⦰➼㸧ࠊ⁐⾑ᛶ㈋⾑➼㸧࡟ᑐࡋ࡚ࠊᙜヱ᪋タཪࡣ㏆㞄་⒪
ᶵ㛵ࡢᑓ㛛ᛶࢆ᭷ࡍࡿ་ᖌ࡜㐃ᦠࡋ㸦๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚ᣦᑟཬࡧᨭ᥼ࢆཷࡅ
ࡽࢀࡿ᮲௳࡟࠶ࡿࡇ࡜㸧
ࠊ┤ࡕ࡟㐺ษ࡞ฎ⨨ࡀ࡛ࡁࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
11
5㸬
㸬ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
࠙Ᏻ඲ᛶࠚ
ձ ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣᮏ๣ࡢᢞ୚ࡀ⚗ᚷ࡜ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᢞ୚ࢆ⾜
ࢃ࡞࠸ࡇ࡜ࠋ
y
ᮏ๣ࡢᡂศ࡟ᑐࡋ㐣ᩄ⑕ࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
ղ ἞⒪๓ࡢホ౯࡟࠾࠸࡚ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢᢞ୚ࡣ᥎ዡࡉࢀ࡞࠸
ࡀࠊ௚ࡢ἞⒪㑅ᢥ⫥ࡀ࡞࠸ሙྜ࡟㝈ࡾࠊៅ㔜࡟ᮏ๣ࢆ౑⏝ࡍࡿࡇ࡜ࢆ⪃៖࡛ࡁࡿࠋ
y
㛫㉁ᛶ⫵⑌ᝈࡢྜేཪࡣ᪤ ࡢ࠶ࡿᝈ⪅
y
⬚㒊⏬ീ᳨ᰝ࡛㛫㉁ᙳࢆㄆࡵࡿᝈ⪅ཬࡧάືᛶࡢᨺᑕ⥺⫵⮚⅖ࡸឤᰁᛶ⫵⅖
➼ࡢ⫵࡟⅖⑕ᛶኚ໬ࡀࡳࡽࢀࡿᝈ⪅
y
⮬ᕫච␿⑌ᝈࡢྜేࠊཪࡣ៏ᛶⓗ࡞ⱝࡋࡃࡣ෌Ⓨᛶࡢ⮬ᕫච␿⑌ᝈࡢ᪤ Ṕࡢ
࠶ࡿᝈ⪅
y
ECOG Performance Status 3-4䠄ὀ1䠅䛾ᝈ⪅
࠙᭷ຠᛶࠚ
ձ ୗグࡢᝈ⪅࡟࠾࠸࡚ᮏ๣ࡢ᭷ຠᛶࡀ᳨ドࡉࢀ࡚࠸ࡿࠋ
y
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿษ㝖୙⬟࡞ϪB ᮇϫᮇཪࡣ෌Ⓨࡢᡥ
ᖹୖ⓶⒴ᝈ⪅
y
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿษ㝖୙⬟࡞ϪB ᮇϫᮇཪࡣ෌Ⓨࡢ㠀
ᡥᖹୖ⓶⒴ᝈ⪅
࡞࠾ࠊ㠀ᡥᖹୖ⓶⒴࡛EGFR㑇ఏᏊኚ␗ཪࡣALK⼥ྜ㑇ఏᏊ㝧ᛶᝈ⪅࡟࠾࠸࡚ࡣࠊ
ཎ๎࡜ࡋ࡚EGFRࢳࣟ࢟ࢩࣥ࢟ࢼ࣮ࢮ㜼ᐖ๣ཪࡣALKࢳࣟ࢟ࢩࣥ࢟ࢼ࣮ࢮ㜼ᐖ๣ࡢ
἞⒪Ṕࢆ᭷ࡍࡿᝈ⪅ࠋ
ղ ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ᑐࡍࡿᮏ๣ࡢᢞ୚ཬࡧ౑⏝᪉ἲ࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢ᭷ຠᛶࡀ
☜❧ࡉࢀ࡚࠾ࡽࡎࠊᮏ๣ࡢᢞ୚ᑐ㇟࡜࡞ࡽ࡞࠸ࠋ
y
໬Ꮫ⒪ἲᮍ἞⒪ࡢᝈ⪅ࠋ
y
⾡ᚋ⿵ຓ໬Ꮫ⒪ἲࠋ
y
௚ࡢᢠᝏᛶ⭘⒆๣࡜ࡢే⏝ࠋ
㸦ὀ1㸧
Score
0
1
2
3
4
ECOG ࡢ Performance Status㸦PS㸧
ᐃ⩏
඲ࡃၥ㢟࡞ࡃάື࡛ࡁࡿࠋⓎ⑓๓࡜ྠࡌ᪥ᖖ⏕άࡀไ㝈࡞ࡃ⾜࠼ࡿࠋ
⫗యⓗ࡟⃭ࡋ࠸άືࡣไ㝈ࡉࢀࡿࡀࠊṌ⾜ྍ⬟࡛ࠊ㍍సᴗࡸᗙࡗ࡚ࡢసᴗࡣ⾜࠺ࡇ࡜ࡀ࡛ࡁࡿࠋ
౛㸸㍍࠸ᐙ஦ࠊ஦ົసᴗ
Ṍ⾜ྍ⬟࡛⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣࡍ࡭࡚ྍ⬟ࡔࡀసᴗࡣ࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࡣ࣋ࢵࢻእ࡛㐣ࡈࡍࠋ
㝈ࡽࢀࡓ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡋ࠿࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࢆ࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
඲ࡃືࡅ࡞࠸ࠋ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣ඲ࡃ࡛ࡁ࡞࠸ࠋ᏶඲࡟࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
12
ճ ⫵⒴デ⒪࢞࢖ࢻࣛ࢖ࣥ㸦᪥ᮏ⫵⒴Ꮫ఍⦅㸧࡟࠾࠸࡚ࠊECOG Performance Status 0㹼1
㸦ὀ 1㸧
࡛ 75 ṓ௨ୖࠊཪࡣ ECOG Performance Status 2㸦ὀ 1㸧ࡢᝈ⪅࡛ࡣࠊ➨ 3 ୡ௦ᢠ⒴
๣㸦ࢻࢭࢱ࢟ࢭࣝ➼㸧ࡢ༢๣ᢞ୚ࡀ᥎ዡࡉࢀ࡚࠾ࡾࠊࣉࣛࢳࢼ〇๣ࡢ౑⏝᥎ዡᗘࡣ
ప࠸ࡓࡵ౑⏝ࡉࢀ࡞࠸ࢣ࣮ࢫࡀ࠶ࡿࠋࡇࡢሙྜࠊࣉࣛࢳࢼ〇๣ࡢ๓἞⒪ࡀ࡞ࡃ࡜ࡶ
➨ 3 ୡ௦ᢠ⒴๣༢๣࡛ࡢ἞⒪Ṕࢆ᭷ࡍࡿᝈ⪅࡟࠾࠸࡚ࡣࠊᮏ๣ࡢᢞ୚ࢆ⪃៖࡛ࡁࡿࠋ
մ ᮏ๣ࡣᾏእ➨Ϫ┦ヨ㦂࡟࠾࠸࡚ࠊᡥᖹୖ⓶⒴ཬࡧ㠀ᡥᖹୖ⓶⒴ࡢ࠸ࡎࢀࡢᝈ⪅࡟࠾
࠸࡚ࡶࢻࢭࢱ࢟ࢭࣝ⩌࡟ᑐࡋ࡚ඃ㉺ᛶࡀ᳨ドࡉࢀ࡚࠸ࡿࠋࡓࡔࡋࠊ㠀ᡥᖹୖ⓶⒴ࡢ
ᝈ⪅࡛ࡣࠊPD-L1Ⓨ⌧⋡࡟ࡼࡾ᭷ຠᛶࡢഴྥࡀ␗࡞ࡿࡇ࡜ࡀ♧၀ࡉࢀࡿ⤖ᯝࡀᚓࡽ
ࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊ㠀ᡥᖹୖ⓶⒴ࡢᝈ⪅࡟࠾࠸࡚ࡣPD-L1Ⓨ⌧⋡ࡶ☜ㄆࡋࡓୖ࡛ᮏ
๣ࡢᢞ୚ྍྰࡢุ᩿ࢆࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ
z
PD-L1Ⓨ⌧⋡ࡀ1%ᮍ‶࡛࠶ࡿࡇ࡜ࡀ☜ㄆࡉࢀࡓ㠀ᡥᖹୖ⓶⒴ᝈ⪅࡟࠾࠸࡚ࡣࠊ
ཎ๎ࠊࢻࢭࢱ࢟ࢭࣝ➼ࡢᮏ๣௨እࡢᢠᝏᛶ⭘⒆๣ࡢᢞ୚ࢆඃඛࡍࡿࠋ㸦ὀ2㸧
z
࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧ࡢࢥࣥࣃࢽ࢜ࣥデ᩿⸆㸦㈍኎ྡ㸸PD-L1 IHC
22C3 pharmDx ࠕࢲࢥࠖ㸧࡟ࡼࡾPD-L1Ⓨ⌧⋡ࢆ☜ㄆࡋࡓ㠀ᡥᖹୖ⓶⒴ࡢᝈ⪅࡛
࠶ࡗ࡚ࠊᮏ๣ࡢデ᩿⸆ 㸦㈍኎ྡ㸸PD-L1 IHC 28-8 pharmDxࠕࢲࢥࠖ㸧࡟ࡼࡿ෌
᳨ᰝࡀᅔ㞴࡞ሙྜ࡟ࡣࠊ௨ୗࡢᩥ⊩➼ࢆཧ⪃࡟ᮏ๣ࡢᢞ୚ࡢྍྰࢆ᳨ウ࡛ࡁࡿࠋ
ᩥ⊩➼㸧
࣭ Andreas H Scheel1 et al.㸸Mod Pathol. 2016; 29: 1165-72
࣭ Fred R. Hirsch et al.㸸J Thorac. Oncol. 2016; 10.1016/j.jtho.2016.11.2228
࣭ Marianne J. Ratcliffe et al.㸸Poster presented at the American Association for
Cancer Research (AACR) Annual Meeting 2016; New Orleans, LA, USA; April
16̽20, 2016
㸦ὀ 2㸧
ࡓࡔࡋࠊ௚ࡢᢠᝏᛶ⭘⒆๣ࡢᢞ୚࡟ࡘ࠸࡚ࠊ⚗ᚷࠊៅ㔜ᢞ୚࡟ヱᙜࡍࡿࡇ࡜ࡢ௚ࠊ⮫ᗋୖၥ㢟࡜࡞
ࡿ๪స⏝ࡢⓎ⌧ࡢ࠾ࡑࢀࡀ࠶ࡿ➼ࠊ་Ꮫ⸆Ꮫୖ୙㐺ᙜ࡜ุ᩿ࡉࢀࡓᝈ⪅㸦ู⣬ཧ↷㸧࡟ࡘ࠸࡚ࡣࡑࡢ㝈ࡾ
࡛ࡣ࡞࠸ࠋ
13
6㸬
㸬ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
ձ ῧ௜ᩥ᭩➼࡟ຍ࠼ࠊ〇㐀㈍኎ᴗ⪅ࡀᥦ౪ࡍࡿ㈨ᩱ➼࡟ᇶ࡙ࡁᮏ๣ࡢ≉ᛶཬࡧ㐺ṇ౑
⏝ࡢࡓࡵ࡟ᚲせ࡞᝟ሗࢆ༑ศ࡟⌮ゎࡋ࡚࠿ࡽ౑⏝ࡍࡿࡇ࡜ࠋ
ղ ἞⒪㛤ጞ࡟ඛ❧ࡕࠊᝈ⪅ཪࡣࡑࡢᐙ᪘࡟᭷ຠᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋࠊྠពࢆᚓ
࡚࠿ࡽᢞ୚ࡍࡿࡇ࡜ࠋ
ճ 㠀ᡥᖹୖ⓶⒴࡟࠾࠸࡚ࡣࠊPD-L1 Ⓨ⌧⋡ࡶ☜ㄆࡋࡓୖ࡛ᮏ๣ࡢᢞ୚ྍྰࢆุ᩿ࡍࡿ
ࡇ࡜ࡀᮃࡲࡋ࠸ࡀࠊPD-L1 Ⓨ⌧⋡ࡀ☜ㄆ࡛ࡁ࡞࠸ሙྜ࡟ࡣࠊᮏ๣ࡢ౑⏝ࡢ㐺ྰࢆ㐺
ษ࡟ุ᩿ࡋࡓୖ࡛ᢞ୚ࡍࡿࡇ࡜ࠋ
մ ୺࡞๪స⏝ࡢ࣐ࢿࢪ࣓ࣥࢺ࡟ࡘ࠸࡚
y
㛫㉁ᛶ⫵⑌ᝈࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚࡟࠶ࡓࡗ࡚ࡣࠊ⮫ᗋ⑕
≧㸦࿧྾ᅔ㞴ࠊတႿࠊⓎ⇕➼㸧ࡢ☜ㄆཬࡧ⬚㒊 X ⥺᳨ᰝࡢᐇ᪋➼ࠊほᐹࢆ༑ศ
࡟⾜࠺ࡇ࡜ࠋࡲࡓࠊᚲせ࡟ᛂࡌ࡚⬚㒊 CTࠊ⾑Ύ࣐࣮࣮࢝➼ࡢ᳨ᰝࢆᐇ᪋ࡍࡿ
ࡇ࡜ࠋ
y
ᮏ๣ࡢᢞ୚ࡣ㔜ᗘࡢ infusion reaction ࡟ഛ࠼࡚⥭ᛴ᫬࡟༑ศ࡞ᑐᛂࡢ࡛ࡁࡿ‽
ഛࢆ⾜ࡗࡓୖ࡛㛤ጞࡍࡿࡇ࡜ࠋࡲࡓࠊ2 ᅇ┠௨㝆ࡢᮏ๣ᢞ୚᫬࡟ infusion reaction
ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡶ࠶ࡿࡢ࡛ࠊᮏ๣ᢞ୚୰ཬࡧᮏ๣ᢞ୚⤊஢ᚋࡣࣂ࢖ࢱࣝࢧ࢖
ࣥࢆ ᐃࡍࡿ➼ࠊᝈ⪅ࡢ≧ែࢆ༑ศ࡟ほᐹࡍࡿࡇ࡜ࠋ࡞࠾ࠊinfusion reaction ࢆ
Ⓨ⌧ࡋࡓሙྜ࡟ࡣࠊ඲࡚ࡢᚩೃཬࡧ⑕≧ࡀ᏶඲࡟ᅇ᚟ࡍࡿࡲ࡛ᝈ⪅ࢆ༑ศほᐹ
ࡍࡿࡇ࡜ࠋ
y
⏥≧⭢ᶵ⬟㞀ᐖࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚㛤ጞ๓ཬࡧᢞ୚ᮇ㛫
୰ࡣᐃᮇⓗ࡟⏥≧⭢ᶵ⬟᳨ᰝ㸦TSHࠊ㐟㞳 T3ࠊ㐟㞳 T4 ➼ࡢ ᐃ㸧ࢆᐇ᪋ࡍࡿ
ࡇ࡜ࠋ
y
ᮏ๣ࡢᢞ୚࡟ࡼࡾࠊ㐣ᗘࡢච␿཯ᛂ࡟㉳ᅉࡍࡿ࡜⪃࠼ࡽࢀࡿᵝࠎ࡞⑌ᝈࡸ⑓ែ
ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࠋ␗ᖖࡀㄆࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓ
ᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿
཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊᮏ๣ࡢఇ⸆ཪࡣ୰Ṇࠊཬࡧ๪⭈⓶㉁࣍
ࣝࣔࣥ๣ࡢᢞ୚➼ࢆ⪃៖ࡍࡿࡇ࡜ࠋ࡞࠾ࠊ๪⭈⓶㉁࣍ࣝࣔࣥࡢᢞ୚࡟ࡼࡾ๪స
⏝ࡢᨵၿࡀㄆࡵࡽࢀ࡞࠸ሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝࣔࣥ௨እࡢච␿ᢚไ๣ࡢ㏣ຍ
ࡶ⪃៖ࡍࡿࠋ
y
ᢞ୚⤊஢ᚋࠊᩘ㐌㛫࠿ࡽᩘ࢝᭶⤒㐣ࡋ࡚࠿ࡽ๪స⏝ࡀⓎ⌧ࡍࡿࡇ࡜ࡀ࠶ࡿࡓࡵࠊ
ᮏ๣ࡢᢞ୚⤊஢ᚋ࡟ࡶ๪స⏝ࡢⓎ⌧࡟༑ศ࡟ὀពࡍࡿࠋ
y
1 ᆺ⢾ᒀ⑓㸦๻⑕ 1 ᆺ⢾ᒀ⑓ࢆྵࡴ㸧ࡀ࠶ࡽࢃࢀࠊ⢾ᒀ⑓ᛶࢣࢺ࢔ࢩࢻ࣮ࢩࢫ
࡟⮳ࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊཱྀῬࠊᝏᚰࠊ჎ྤ➼ࡢ⑕≧ࡢⓎ⌧ࡸ⾑⢾್ࡢୖ᪼࡟༑
ศὀពࡍࡿࡇ࡜ࠋ1 ᆺ⢾ᒀ⑓ࡀ␲ࢃࢀࡓሙྜ࡟ࡣᢞ୚ࢆ୰Ṇࡋࠊ࢖ࣥࢫࣜࣥ〇
๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇ࡜ࠋ
յ ᮏ๣ࡢ⮫ᗋヨ㦂࡟࠾࠸࡚ࠊᢞ୚㛤ጞ࠿ࡽ 9 㐌┠ࠊࡑࢀ௨㝆ࡣࠊᢞ୚㛤ጞ࠿ࡽ 1 ᖺ㛫
ࡣ 3 ᅇᢞ୚⤊஢ࡈ࡜࡟᭷ຠᛶࡢホ౯ࢆ⾜ࡗ࡚࠸ࡓࡇ࡜ࢆཧ⪃࡟ࠊᮏ๣ᢞ୚୰ࡣᐃᮇ
ⓗ࡟⏬ീ᳨ᰝ࡛ຠᯝࡢ☜ㄆࢆ⾜࠺ࡇ࡜ࠋ
14
㸦ὀ 2㸧ู⣬
⚗ᚷࠊៅ㔜ᢞ୚ࠊ⮫ᗋୖၥ㢟࡜࡞ࡿ๪స⏝ࡢཧ⪃஦౛
㸺ࢻࢭࢱ࢟ࢭࣝࡀ⚗ᚷ࡜࡞ࡿᝈ⪅㸼
㔜⠜࡞㦵㧊ᢚไࡢ࠶ࡿᝈ⪅
ឤᰁ⑕ࢆྜేࡋ࡚࠸ࡿᝈ⪅
Ⓨ⇕ࢆ᭷ࡋឤᰁ⑕ࡢ␲ࢃࢀࡿᝈ⪅
౑⏝⸆๣࡟㐣ᩄ⑕ࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿᝈ⪅
㸺ࢻࢭࢱ࢟ࢭࣝࡀៅ㔜ᢞ୚࡜࡞ࡿᝈ⪅㸼
㦵㧊ᢚไࡢ࠶ࡿᝈ⪅
㛫㉁ᛶ⫵⅖ཪࡣ⫵⥺⥔⑕ࡢ࠶ࡿᝈ⪅
⫢㞀ᐖࡢ࠶ࡿᝈ⪅
⭈㞀ᐖࡢ࠶ࡿᝈ⪅
ᾋ⭘ࡢ࠶ࡿᝈ⪅
ዷፎࡍࡿྍ⬟ᛶࡢ࠶ࡿᝈ⪅
㸺ࢻࢭࢱ࢟ࢭࣝࡢ㔜኱࡞๪స⏝㸼
㦵㧊ᢚไ
ࢩࣙࢵࢡ⑕≧࣭࢔ࢼࣇ࢕ࣛ࢟ࢩ࣮
㯤⑇ࠊ⫢୙඲ࠊ⫢ᶵ⬟㞀ᐖ
ᛴᛶ⭈୙඲
㛫㉁ᛶ⫵⅖ࠊ⫵⥺⥔⑕
ᚰ୙඲
᧛✀ᛶ⾑⟶ෆจᅛ⑕ೃ⩌㸦DIC㸧
⭠⟶✸Ꮝࠊ⫶⭠ฟ⾑ࠊ⹫⾑ᛶ኱⭠⅖ࠊ኱⭠⅖
࢖ࣞ࢘ࢫ
ᛴᛶ࿧྾ಁ㏕⑕ೃ⩌
ᛴᛶ⮅⅖
⓶⭵⢓⭷║⑕ೃ⩌㸦Stevens̺Johnson ⑕ೃ⩌㸧
ࠊ୰ẘᛶ⾲⓶ቯṚ⑕㸦Lyell ⑕ೃ⩌㸧
ࠊከᙧ⣚ᩬ
ᚰࢱ࣏ࣥࢼ࣮ࢹࠊ⫵Ỉ⭘ࠊᾋ⭘࣭యᾮ㈓␃
ᚰ➽᱾ሰࠊ㟼⬦⾑ᰦሰᰦ⑕
ឤᰁ⑕
ᢠ฼ᒀ࣍ࣝࣔࣥ୙㐺ྜศἪ⑕ೃ⩌㸦SIADH㸧
㔜⠜࡞ཱྀෆ⅖➼ࡢ⢓⭷⅖ࠊ⾑⟶⅖ࠊᮎᲈ⚄⤒㞀ᐖࠊᅄ⫥ࡢ⬺ຊឤ➼ࡢᮎᲈᛶ㐠ື㞀ᐖࠊRadiation
Recall ⌧㇟
15
ูῧ㸰
᭱㐺౑⏝᥎㐍࢞࢖ࢻࣛ࢖ࣥ
ࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧
㸦㈍኎ྡ㸸࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 20 mgࠊ࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 100 mg㸧
㹼ᝏᛶ㯮Ⰽ⭘㹼
ᖹᡂ㸰㸷ᖺ㸰᭶
ཌ⏕ປാ┬
┠ḟ
㻌
1. ࡣࡌࡵ࡟
2. ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
3. ⮫ᗋᡂ⦼
P2
P3
P4
4. ᪋タ࡟ࡘ࠸࡚
5. ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
6. ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
P10
P12
P13
㻌
㻌
1
1㸬
㸬ࡣࡌࡵ࡟
་⸆ရࡢ᭷ຠᛶ࣭Ᏻ඲ᛶࡢ☜ಖࡢࡓࡵ࡟ࡣࠊῧ௜ᩥ᭩➼࡟ᇶ࡙࠸ࡓ㐺ṇ࡞౑⏝ࡀồࡵ
ࡽࢀࡿࠋࡉࡽ࡟ࠊ㏆ᖺࡢ⛉Ꮫᢏ⾡ࡢ㐍Ṍ࡟ࡼࡾࠊᢠయ་⸆ရ࡞࡝ࡢ㠉᪂ⓗ࡞᪂つస⏝ᶵ
ᗎ་⸆ရࡀᢎㄆࡉࢀࡿ୰࡛ࠊࡇࢀࡽࡢ་⸆ရࢆ┿࡟ᚲせ࡞ᝈ⪅࡟ᥦ౪ࡍࡿࡇ࡜ࡀႚ⥭ࡢ
ㄢ㢟࡜࡞ࡗ࡚࠾ࡾࠊ
⤒῭㈈ᨻ㐠Ⴀ࡜ᨵ㠉ࡢᇶᮏ᪉㔪 2016
㸦ᖹᡂ 28 ᖺ㸴᭶㸰᪥㛶㆟Ỵᐃ㸧
࡟࠾࠸࡚ࡶࠊ㠉᪂ⓗ་⸆ရ➼ࡢ౑⏝ࡢ᭱㐺໬᥎㐍ࢆᅗࡿࡇ࡜࡜ࡉࢀ࡚࠸ࡿࠋ
᪂つస⏝ᶵᗎ་⸆ရࡣࠊ⸆⌮స⏝ࡸᏳ඲ᛶࣉࣟࣇ࢓࢖ࣝࡀ᪤Ꮡࡢ་⸆ရ࡜᫂ࡽ࠿࡟␗
࡞ࡿࡇ࡜ࡀ࠶ࡿࠋࡇࡢࡓࡵࠊ᭷ຠᛶཬࡧᏳ඲ᛶ࡟㛵ࡍࡿ᝟ሗࡀ༑ศ⵳✚ࡍࡿࡲ࡛ࡢ㛫ࠊ
ᙜヱ་⸆ရࡢᜠᜨࢆᙉࡃཷࡅࡿࡇ࡜ࡀᮇᚅࡉࢀࡿᝈ⪅࡟ᑐࡋ࡚౑⏝ࡍࡿ࡜࡜ࡶ࡟ࠊ๪స
⏝ࡀⓎ⌧ࡋࡓ㝿࡟ᚲせ࡞ᑐᛂࢆ࡜ࡿࡇ࡜ࡀྍ⬟࡞୍ᐃࡢせ௳ࢆ‶ࡓࡍ་⒪ᶵ㛵࡛౑⏝
ࡍࡿࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ
ࡋࡓࡀࡗ࡚ࠊᮏ࢞࢖ࢻࣛ࢖࡛ࣥࡣࠊ㛤Ⓨẁ㝵ࡸࡇࢀࡲ࡛࡟ᚓࡽࢀ࡚࠸ࡿ་Ꮫ⸆Ꮫⓗ࣭
⛉Ꮫⓗぢᆅ࡟ᇶ࡙ࡁࠊ௨ୗࡢ་⸆ရࡢ᭱㐺࡞౑⏝ࢆ᥎㐍ࡍࡿほⅬ࠿ࡽᚲせ࡞せ௳ࠊ⪃࠼
᪉ཬࡧ␃ព஦㡯ࢆ♧ࡍࠋ
࡞࠾ࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ⊂❧⾜ᨻἲே་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓࠊබ┈♫ᅋἲே᪥ᮏ
⮫ᗋ⭘⒆Ꮫ఍ࠊ୍⯡♫ᅋἲே᪥ᮏ⮫ᗋෆ⛉་఍ཬࡧබ┈♫ᅋἲே᪥ᮏ⓶⭵⛉Ꮫ఍ࡢ༠ຊ
ࡢࡶ࡜సᡂࡋࡓࠋ
ᑐ㇟࡜࡞ࡿ་⸆ရ㸸࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 20 mgࠊ࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 100 mg㸦୍⯡ྡ㸸
ࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧㸧
ᑐ㇟࡜࡞ࡿຠ⬟ཪࡣຠᯝ㸸᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘
ᑐ㇟࡜࡞ࡿ⏝ἲཬࡧ⏝㔞㸸㸺໬Ꮫ⒪ἲᮍ἞⒪ࡢ᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘ᝈ⪅ࡢሙྜ㸼
㏻ᖖࠊᡂே࡟ࡣࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧࡜ࡋ࡚ࠊ1 ᅇ 3mg/kg
㸦య㔜㸧ࢆ 2 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡍࡿࠋ
㸺໬Ꮫ⒪ἲ᪤἞⒪ࡢ᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘ᝈ⪅ࡢሙྜ㸼
㏻ᖖࠊᡂே࡟ࡣࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧࡜ࡋ࡚ࠊ1 ᅇ 3mg/kg
㸦య㔜㸧ࢆ 2 㐌㛫㛫㝸ཪࡣ 1 ᅇ 2mg/kg㸦య㔜㸧ࢆ 3 㐌㛫㛫㝸࡛Ⅼ
⁲㟼ὀࡍࡿࠋ
〇㐀㈍ ኎ ᴗ ⪅㸸ᑠ㔝⸆ရᕤᴗᰴᘧ఍♫
2
2㸬
㸬ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
࢜ࣉࢪ࣮࣎Ⅼ⁲㟼ὀ 20 mg ཬࡧ 100 mg㸦୍⯡ྡ㸸ࢽ࣐࣎ࣝࣈ㸦㑇ఏᏊ⤌᥮࠼㸧ࠊ௨ୗࠊ
ࠕᮏ๣ࠖ㸧ࡣࠊᑠ㔝⸆ရᕤᴗᰴᘧ఍♫࡜࣓ࢲࣞࢵࢡࢫ♫㸦⌧ࣈࣜࢫࢺ࣭࣐ࣝ࢖࣮ࣖࢬ ࢫ
ࢡ࢖ࣈ㸦BMS㸧♫㸧ࡀ㛤Ⓨࡋࡓࣄࢺ PD-1㸦Programmed cell death-1㸧࡟ᑐࡍࡿࣄࢺᆺ IgG4
ࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡿࠋ
PD-1 ࡣࠊάᛶ໬ࡋࡓࣜࣥࣃ⌫㸦T ⣽⬊ࠊB ⣽⬊ཬࡧࢼࢳ࣮ࣗࣛࣝ࢟ࣛT ⣽⬊㸧ཬࡧ㦵
㧊⣔⣽⬊࡟Ⓨ⌧ࡍࡿ CD28 ࣇ࢓࣑࣮ࣜ㸦T ⣽⬊ࡢάᛶ໬ࢆ⿵ຓⓗ࡟ṇ࡜㈇࡟ไᚚࡍࡿศ
Ꮚ⩌㸧࡟ᒓࡍࡿཷᐜయ࡛࠶ࡿࠋPD-1 ࡣᢠཎᥦ♧⣽⬊࡟Ⓨ⌧ࡍࡿ PD-1 ࣜ࢞ࣥࢻ㸦PD-L1
ཬࡧ PD-L2㸧࡜⤖ྜࡋࠊࣜࣥࣃ⌫࡟ᢚไᛶࢩࢢࢼࣝࢆఏ㐩ࡋ࡚ࣜࣥࣃ⌫ࡢάᛶ໬≧ែࢆ
㈇࡟ㄪ⠇ࡋ࡚࠸ࡿࠋPD-1 ࣜ࢞ࣥࢻࡣᢠཎᥦ♧⣽⬊௨እ࡟ࣄࢺࡢᵝࠎ࡞⭘⒆⤌⧊࡟Ⓨ⌧
ࡋ࡚࠾ࡾࠊᝏᛶ㯮Ⰽ⭘ᝈ⪅࠿ࡽษ㝖ࡋࡓ⭘⒆⤌⧊࡟࠾ࡅࡿ PD-L1 ࡢⓎ⌧࡜⾡ᚋࡢ⏕Ꮡ
ᮇ㛫࡜ࡢ㛫࡟㈇ࡢ┦㛵㛵ಀࡀ࠶ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ㸦Cancer 2010; 116: 1757-66㸧
ࠋ
ࡲࡓࠊᝏᛶ㯮Ⰽ⭘ᝈ⪅࡛ࡣ⤌⧊ᾐ₶ T ⣽⬊ࡀ⏘⏕ࡍࡿ࢖ࣥࢱ࣮ࣇ࢙࣐ࣟࣥ࢞ࣥ㸦IFN-γ㸧
࡟ࡼࡗ࡚ PD-L1 ࡢⓎ⌧ࡀㄏᑟࡉࢀࠊ㌿⛣ࡋࡓ⭘⒆⤌⧊࡟࠾ࡅࡿ PD-L1 ࡢⓎ⌧࡜⾡ᚋࡢ
⏕Ꮡᮇ㛫࡜ࡢ㛫࡟ṇࡢ┦㛵㛵ಀࡀ࠶ࡿ࡜ࡢሗ࿌ࡶ࠶ࡿ 㸦Sci Transl Med 2012: 28:
127ra37㸧
ࠋࡉࡽ࡟ࠊPD-L1 ࢆᙉไⓎ⌧ࡉࡏࡓࡀࢇ⣽⬊ࡣࠊᢠཎ≉␗ⓗ CD8 㝧ᛶ T ⣽⬊
ࡢ⣽⬊യᐖάᛶࢆῶᙅࡉࡏࡿࡀࠊᢠ PD-L1 ᢠయ࡛ PD-1 ࡜ PD-L1 ࡜ࡢ⤖ྜࢆ㜼ᐖࡍࡿ࡜
ࡑࡢ⣽⬊യᐖάᛶࡀᅇ᚟ࡍࡿࡇ࡜ࡀ♧ࡉࢀ࡚࠸ࡿࠊ➼ࡢࡇ࡜࠿ࡽ PD-1/PD-1 ࣜ࢞ࣥࢻ⤒
㊰ࡣࠊࡀࢇ⣽⬊ࡀᢠཎ≉␗ⓗ࡞ T ⣽⬊࠿ࡽࡢᨷᧁ➼ࢆᅇ㑊ࡍࡿᶵᗎࡢ୍ࡘ࡜ࡋ࡚⪃࠼ࡽ
ࢀ࡚࠸ࡿࠋ
ᮏ๣ࡣࠊ⸆⌮ヨ㦂ࡢ⤖ᯝ࠿ࡽ PD-1 ࡢ⣽⬊እ㡿ᇦ㸦PD-1 ࣜ࢞ࣥࢻ⤖ྜ㡿ᇦ㸧࡟⤖ྜࡋࠊ
PD-1 ࡜ PD-1 ࣜ࢞ࣥࢻ࡜ࡢ⤖ྜࢆ㜼ᐖࡍࡿࡇ࡜࡟ࡼࡾࠊࡀࢇᢠཎ≉␗ⓗ࡞ T ⣽⬊ࡢάᛶ
໬ཬࡧࡀࢇ⣽⬊࡟ᑐࡍࡿ⣽⬊യᐖάᛶࢆቑᙉࡍࡿࡇ࡜࡛ᣢ⥆ⓗ࡞ᢠ⭘⒆ຠᯝࢆ♧ࡍࡇ
࡜ࡀ☜ㄆࡉࢀ࡚࠸ࡿࠋ
ᮏ๣ࡢస⏝ᶵᗎ࡟ᇶ࡙ࡃ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝➼ࡀ࠶ࡽࢃࢀࠊ㔜⠜ཪࡣṚஸ࡟
⮳ࡿྍ⬟ᛶࡀ࠶ࡿࠋᮏ๣ࡢᢞ୚୰ཬࡧᢞ୚ᚋ࡟ࡣࠊᝈ⪅ࡢほᐹࢆ༑ศ࡟⾜࠸ࠊ␗ᖖࡀㄆ
ࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺
ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝ
ࣔࣥ๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ᚲせࡀ࠶ࡿࠋ
㻌
㻌
3
3㸬
㸬⮫ᗋᡂ⦼
᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘ࡢᢎㄆ᫬࡟ホ౯ࢆ⾜ࡗࡓ୺࡞⮫ᗋヨ㦂ࡢᡂ⦼ࢆ♧ࡍࠋ
࠙᭷ຠᛶࠚ
ձᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-02 ヨ㦂㸧
ࢲ࢝ࣝࣂࢪࣥ㸦௨ୗࠊ
ࠕDTICࠖ
㸧࡟ࡼࡿ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿ᰿἞ษ㝖୙⬟࡞Ϫᮇϫᮇཪ
ࡣ෌Ⓨࡢᝏᛶ㯮Ⰽ⭘ᝈ⪅
㸦ECOG Performance Status 0 ཬࡧ 1㸧
35 ౛ࢆᑐ㇟࡟ࠊᮏ๣ 2 mg/kg
ࢆ 3 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡋࡓࠋ୺せホ౯㡯┠࡛࠶ࡿዌຠ⋡㸦RECIST ࢞࢖ࢻࣛ࢖ࣥ 1.1
∧࡟ᇶ࡙ࡃ୰ኸุᐃ࡟ࡼࡿ CR ཪࡣ PR㸧ࡣ 22.9%㸦90%ಙ㢗༊㛫㸸13.4㹼36.2%㸧࡛࠶
ࡗࡓࠋ࡞࠾ࠊ஦๓࡟タᐃࡋࡓ㜈್ࡣ 12.5%࡛࠶ࡗࡓࠋ
ղᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-08 ヨ㦂㸧
໬Ꮫ ⒪ἲᮍ἞⒪ ࡢ᰿἞ษ㝖 ୙⬟࡞ Ϫᮇ ϫᮇཪࡣ ෌Ⓨࡢᝏᛶ 㯮Ⰽ⭘ᝈ⪅ 㸦 ECOG
Performance Status 0 ཬࡧ 1㸧24 ౛ࢆᑐ㇟࡟ࠊᮏ๣ 3 mg/kg ࢆ 2 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡋࡓࠋ
୺せホ౯㡯┠࡛࠶ࡿዌຠ⋡㸦RECIST ࢞࢖ࢻࣛ࢖ࣥ 1.1 ∧࡟ᇶ࡙ࡃ୰ኸุᐃ࡟ࡼࡿ CR
ཪࡣ PR㸧ࡣ 29.2%㸦90%ಙ㢗༊㛫㸸16.7㹼45.9%㸧࡛࠶ࡗࡓࠋ࡞࠾ࠊ஦๓࡟タᐃࡋࡓ㜈
್ࡣ 6.0%࡛࠶ࡗࡓࠋ
ճᾏእ➨Ϫ┦ヨ㦂㸦CA209066 ヨ㦂㸧1㸧
v-raf ࣐࢘ࢫ⫗⭘࢘࢕ࣝࢫ⒴㑇ఏᏊ⏘≀࣍ࣔࣟࢢ B1㸦௨ୗࠊ
ࠕBRAFࠖ
㸧 V600 ኚ␗ࡢ࡞
࠸໬Ꮫ⒪ἲᮍ἞⒪ࡢ᰿἞ษ㝖୙⬟࡞Ϫᮇϫᮇཪࡣ෌Ⓨࡢᝏᛶ㯮Ⰽ⭘ᝈ⪅㸦ECOG
Performance Status 0 ཬࡧ 1㸧418 ౛㸦ᮏ๣⩌ 210 ౛ࠊDTIC ⩌ 208 ౛㸧ࢆᑐ㇟࡟ࠊDTIC
ࢆᑐ↷࡜ࡋ࡚ᮏ๣ 3 mg/kg ࢆ 2 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡋࡓ࡜ࡁࡢ᭷ຠᛶཬࡧᏳ඲ᛶࢆ᳨ウ
ࡋࡓࠋ୺せホ౯㡯┠࡛࠶ࡿ඲⏕Ꮡᮇ㛫㸦୰ኸ್㹙95%ಙ㢗༊㛫㹛
㸧ࡣࠊᮏ๣⩌ࡣ NE㹙NE
㹼NE㹛࢝᭶ࠊDTIC ⩌࡛ 10.84㹙9.33㹼12.09㹛࢝᭶࡛࠶ࡾࠊᮏ๣ࡣ DTIC ࡟ᑐࡋ⤫ィᏛ
ⓗ࡟᭷ព࡞ᘏ㛗ࢆ♧ࡋࡓ㸦ࣁࢨ࣮ࢻẚ 0.42㹙99.79%ಙ㢗༊㛫㸸0.25㹼0.73㹛
ࠊp<0.0001㹙ᒙ
ู log-rank ᳨ᐃ㹛
㸧
ࠋ
4
OS ࡢ Kaplan-Meier ᭤⥺
մᾏእ➨Ϫ┦ヨ㦂㸦CA209037 ヨ㦂㸧2㸧
࢖ࣆ࣒࣐ࣜࣈ㸦㑇ఏᏊ⤌᥮࠼㸧ཪࡣ BRAF 㜼ᐖ๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿ᰿἞ษ㝖୙
⬟࡞Ϫᮇϫᮇཪࡣ෌Ⓨࡢᝏᛶ㯮Ⰽ⭘ᝈ⪅㸦ECOG Performance Status 0 ཬࡧ 1㸧405 ౛㸦ᮏ
๣⩌ 272 ౛ࠊ໬Ꮫ⒪ἲ㸦DTIC ཪࡣ࢝ࣝ࣎ࣉࣛࢳࣥ࡜ࣃࢡࣜࢱ࢟ࢭࣝ࡜ࡢే⏝㸧⩌ 133
౛㸧ࢆᑐ㇟࡟ࠊ໬Ꮫ⒪ἲࢆᑐ↷࡜ࡋ࡚ᮏ๣ 3 mg/kg ࢆ 2 㐌㛫㛫㝸࡛Ⅼ⁲㟼ὀࡋࡓ࡜ࡁࡢ
᭷ຠᛶཬࡧᏳ඲ᛶࢆ᳨ウࡋࡓࠋ୺せホ౯㡯┠࡛࠶ࡿዌຠ⋡㸦RECIST ࢞࢖ࢻࣛ࢖ࣥ 1.1
∧࡟ᇶ࡙ࡃ୰ኸุᐃ࡟ࡼࡿ CR ཪࡣ PR㸧ࡣࠊᮏ๣ࡀᢞ୚ࡉࢀࡓ᭱ึࡢ 120 ౛ࡀゎᯒᑐ
㇟㞟ᅋ࡜ࡉࢀࠊᮏ๣⩌࡛ 31.7%㸦95%ಙ㢗༊㛫㸸23.5㹼40.8%㸧࡛࠶ࡗࡓࠋ࡞࠾ࠊ஦๓࡟
ዌຠ⋡ࡢ㜈್ࡣタᐃࡋ࡚࠸࡞࠿ࡗࡓࠋࡶ࠺୍ࡘࡢ୺せホ౯㡯┠࡛࠶ࡿ඲⏕Ꮡᮇ㛫㸦୰ኸ
್㹙95%ಙ㢗༊㛫㹛
㸧࡟ࡘ࠸࡚ 182 ౛ࡢ࢖࣋ࣥࢺ㸦Ṛஸ㸧ᩘ࡟࡚୰㛫ゎᯒࢆ⾜ࡗࡓ⤖ᯝࠊ
ᮏ๣⩌ࡣ 15.47㹙12.39㹼NE㹛࢝᭶ࠊ໬Ꮫ⒪ἲ⩌࡛ 13.67㹙11.50㹼NE㹛࢝᭶࡛࠶ࡾࠊᮏ๣
ࡣ໬Ꮫ⒪ἲ࡟ᑐࡋ⤫ィᏛⓗ࡟᭷ព࡞ᘏ㛗ࢆ♧ࡉ࡞࠿ࡗࡓ㸦ࣁࢨ࣮ࢻẚ 0.93㹙95%ಙ㢗༊
㛫㸸0.68㹼1.26㹛
ࠊp=0.6299㹙ᒙู log-rank ᳨ᐃ㹛
㸧
ࠋ
࠙Ᏻ඲ᛶࠚ
ձᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-02 ヨ㦂㸧
᭷ᐖ஦㇟ࡣ඲౛㸦100%㸧࡟ㄆࡵࡽࢀࠊᮏ⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ஦㇟ࡣ 30/35
౛㸦85.7%㸧࡟ㄆࡵࡽࢀࡓࠋⓎ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ࡜࠾ࡾ࡛࠶ࡗࡓࠋ
5
Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝
౛ᩘ㸦%㸧
35 ౛
඲ Grade
Grade 3 ௨ୖ
30㸦85.7㸧
9㸦25.7㸧
ჾᐁู኱ศ㢮
ᇶᮏㄒ
㸦MedDRA/J ver.16.0㸧
඲๪స⏝
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟పୗ⑕
⫶⭠㞀ᐖ
ୗ⑩
ᝏᚰ
ཱྀෆ⅖
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
⑂ປ
೏ᛰឤ
Ⓨ⇕
⫢⫹㐨⣔㞀ᐖ
⫢㞀ᐖ
⮫ᗋ᳨ᰝ
ALT ቑຍ
AST ቑຍ
⾑୰࢔ࣝࣈ࣑ࣥῶᑡ
⾑୰ CK ቑຍ
⾑୰ࢡࣞ࢔ࢳࢽࣥቑຍ
⾑୰ࣈࢻ࢘⢾ቑຍ
⾑୰ LDH ቑຍ
⾑୰ TSH ῶᑡ
⾑୰ TSH ቑຍ
CRP ቑຍ
ዲ㓟⌫ᩘቑຍ
γ-GTP ቑຍ
ᒀ୰ࣈࢻ࢘⢾㝧ᛶ
࣊ࣔࢢࣟࣅࣥῶᑡ
ࣜࣥࣃ⌫ᩘῶᑡ
ዲ୰⌫ᩘῶᑡ
㓟⣲㣬࿴ᗘపୗ
⾑ᑠᯈᩘῶᑡ
㉥⾑⌫ᩘῶᑡ
ⓑ⾑⌫ᩘῶᑡ
㐟㞳 T3 ቑຍ
㐟㞳 T3 ῶᑡ
㐟㞳 T4 ῶᑡ
㐟㞳 T4 ቑຍ
࣐ࣜ࢘ࢳᅉᏊቑຍ
⾑୰ ALP ቑຍ
ᢠ⏥≧⭢ᢠయ㝧ᛶ
⣽⬊࣐࣮࣮࢝ቑຍ
ᢠ᰾ᢠయቑຍ
ࢧ࣮ࣇ࢓ࢡࢱࣥࢺࣉࣟࢸ࢖ࣥቑຍ
⾑୰ CK ῶᑡ
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ
➽②⦰
⚄⤒⣔㞀ᐖ
࿡ぬ㞀ᐖ
ᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
ⓑᩬ
ࡑ࠺⑛⑕
Ⓨ⑈
ᩬ≧ୣ⑈≧⓶⑈
⬡₃ᛶ⓶⭵⅖
⓶⭵Ⰽ⣲ῶᑡ
6
5㸦14.3㸧
0
4㸦11.4㸧
2㸦5.7㸧
2㸦5.7㸧
1㸦2.9㸧
1㸦2.9㸧
0
5㸦14.3㸧
2㸦5.7㸧
3㸦8.6㸧
0
0
0
2㸦5.7㸧
2㸦5.7㸧
4㸦11.4㸧
5㸦14.3㸧
2㸦5.7㸧
5㸦14.3㸧
2㸦5.7㸧
2㸦5.7㸧
5㸦14.3㸧
3㸦8.6㸧
7㸦20.0㸧
5㸦14.3㸧
4㸦11.4㸧
4㸦11.4㸧
2㸦5.7㸧
3㸦8.6㸧
5㸦14.3㸧
2㸦5.7㸧
2㸦5.7㸧
2㸦5.7㸧
2㸦5.7㸧
6㸦17.1㸧
2㸦5.7㸧
8㸦22.9㸧
6㸦17.1㸧
2㸦5.7㸧
3㸦8.6㸧
5㸦14.3㸧
3㸦8.6㸧
2㸦5.7㸧
2㸦5.7㸧
4㸦11.4㸧
2㸦5.7㸧
1㸦2.9㸧
2㸦5.7㸧
0
3㸦8.6㸧
0
0
1㸦2.9㸧
0
0
1㸦2.9㸧
0
4㸦11.4㸧
0
1㸦2.9㸧
1㸦2.9㸧
1㸦2.9㸧
0
1㸦2.9㸧
1㸦2.9㸧
0
0
0
0
0
0
1㸦2.9㸧
0
0
0
0
0
2㸦5.7㸧
0
2㸦5.7㸧
2㸦5.7㸧
0
0
6㸦17.1㸧
11㸦31.4㸧
2㸦5.7㸧
2㸦5.7㸧
2㸦5.7㸧
4㸦11.4㸧
0
0
0
0
0
0
࡞࠾ࠊ㛫㉁ᛶ⫵⑌ᝈ 1 ౛㸦2.9%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 1 ౛㸦2.9%㸧ࠊ⚄⤒㞀ᐖ 4
౛㸦11.4%㸧ࠊ⫢ᶵ⬟㞀ᐖ 5 ౛㸦14.3%㸧ࠊ⭈ᶵ⬟㞀ᐖ 2 ౛㸦5.7%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ 8
౛㸦22.9%㸧ࠊ๪⭈㞀ᐖ 1 ౛㸦2.9%㸧ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ 1 ౛㸦2.9%㸧ཬࡧࡪ࡝࠺⭷⅖ 1
౛㸦2.9%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊୗᆶయᶵ⬟㞀ᐖࠊinfusion reactionࠊ1 ᆺ⢾ᒀ⑓ࠊ⮅⅖ࠊ
㔜⑕➽↓ຊ⑕ࠊ⬻⅖࣭㧊⭷⅖ࠊᚰ➽⅖ࠊ➽⅖ࠊ⫢⅖ࠊᶓ⣠➽⼥ゎ⑕ཬࡧච␿ᛶ⾑ᑠᯈῶ
ᑡᛶ⣸ᩬ⑓ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
ղᅜෆ➨ϩ┦ヨ㦂㸦ONO-4538-08 ヨ㦂㸧
᭷ᐖ஦㇟ࡣ 22/24 ౛㸦91.7%㸧࡟ㄆࡵࡽࢀࠊ἞㦂⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ஦
㇟ࡣ 18/24 ౛㸦75.0%㸧࡟ㄆࡵࡽࢀࡓࠋⓎ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ࡜࠾ࡾ࡛࠶ࡗ
ࡓࠋ
Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝
౛ᩘ㸦%㸧
24 ౛
඲ Grade
Grade 3 ௨ୖ
18㸦75.0㸧
2㸦8.3㸧
ჾᐁู኱ศ㢮
ᇶᮏㄒ
㸦MedDRA/J ver.18.0㸧
඲๪స⏝
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟పୗ⑕
⫶⭠㞀ᐖ
ᝏᚰ
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
೏ᛰឤ
⮫ᗋ᳨ᰝ
య㔜ῶᑡ
௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ
㣗ḧῶ㏥
࿧྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ
Ⓨኌ㞀ᐖ
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
ⓑᩬ
ࡑ࠺⑛⑕
ᩬ≧ୣ⑈≧⓶⑈
6㸦25.0㸧
0
2㸦8.3㸧
0
4㸦16.7㸧
0
2㸦8.3㸧
0
2㸦8.3㸧
0
2㸦8.3㸧
0
5㸦20.8㸧
5㸦20.8㸧
2㸦8.3㸧
0
0
0
࡞࠾ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 2 ౛㸦8.3%㸧ࠊ⫢ᶵ⬟㞀ᐖ 1 ౛㸦4.2%㸧ࠊୗᆶయᶵ⬟㞀
ᐖ 1 ౛㸦4.2%㸧ཬࡧ⏥≧⭢ᶵ⬟㞀ᐖ 7 ౛㸦29.2%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ㛫㉁ᛶ⫵⑌ᝈࠊ
⚄⤒㞀ᐖ㸦ࢠ࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧ࠊ๪⭈㞀ᐖࠊ
infusion reactionࠊ1 ᆺ⢾ᒀ⑓ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁
⒔➼㸧ࠊ⮅⅖ࠊ㔜⑕➽↓ຊ⑕ࠊ⬻⅖࣭㧊⭷⅖ࠊࡪ࡝࠺⭷⅖ࠊᚰ➽⅖ࠊ➽⅖ࠊ⫢⅖ࠊᶓ⣠
➽⼥ゎ⑕ཬࡧච␿ᛶ⾑ᑠᯈῶᑡᛶ⣸ᩬ⑓ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
ճᾏእ➨Ϫ┦ヨ㦂㸦CA209066 ヨ㦂㸧1㸧
᭷ᐖ஦㇟ࡣᮏ⸆⩌ 192/206 ౛㸦93.2%㸧
ࠊDTIC ⩌ 194/205 ౛㸦94.6%㸧࡟ㄆࡵࡽࢀࠊ἞㦂
⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ஦㇟ࡣᮏ⸆⩌ 153/206 ౛㸦74.3%㸧
ࠊDTIC ⩌ 155/205
౛㸦75.6%㸧࡟ㄆࡵࡽࢀࡓࠋ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ࡜࠾ࡾ
࡛࠶ࡗࡓࠋ
7
࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝
ჾᐁู኱ศ㢮
ᇶᮏㄒ
㸦MedDRA/J ver.17.0㸧
඲๪స⏝
⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ
ዲ୰⌫ῶᑡ⑕
⾑ᑠᯈῶᑡ⑕
⫶⭠㞀ᐖ
౽⛎
ୗ⑩
ᝏᚰ
჎ྤ
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
↓ຊ⑕
⑂ປ
Ⓨ⇕
௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ
㣗ḧῶ㏥
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ
㛵⠇③
⚄⤒⣔㞀ᐖ
㢌③
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
⣚ᩬ
ග⥺㐣ᩄᛶ཯ᛂ
ࡑ࠺⑛⑕
Ⓨ⑈
ᑜᖖᛶⓑᩬ
౛ᩘ㸦%㸧
ᮏ⸆⩌
DTIC ⩌
206 ౛
205 ౛
඲ Grade
Grade 3 ௨ୖ
඲ Grade
Grade 3 ௨ୖ
153㸦74.3㸧
24㸦11.7㸧
155㸦75.6㸧
36㸦17.6㸧
0
0
0
0
23㸦11.2㸧
21㸦10.2㸧
9㸦4.4㸧
10㸦4.9㸧
22㸦10.7㸧
33㸦16.0㸧
34㸦16.5㸧
13㸦6.3㸧
0
2㸦1.0㸧
0
1㸦0.5㸧
25㸦12.2㸧
32㸦15.6㸧
85㸦41.5㸧
43㸦21.0㸧
0
1㸦0.5㸧
0
1㸦0.5㸧
21㸦10.2㸧
41㸦19.9㸧
15㸦7.3㸧
0
0
0
25㸦12.2㸧
30㸦14.6㸧
10㸦4.9㸧
1㸦0.5㸧
2㸦1.0㸧
1㸦0.5㸧
11㸦5.3㸧
0
19㸦9.3㸧
0
12㸦5.8㸧
0
3㸦1.5㸧
0
9㸦4.4㸧
0
14㸦6.8㸧
0
13㸦6.3㸧
3㸦1.5㸧
35㸦17.0㸧
31㸦15.0㸧
22㸦10.7㸧
0
0
1㸦0.5㸧
1㸦0.5㸧
0
4㸦2.0㸧
11㸦5.4㸧
11㸦5.4㸧
6㸦2.9㸧
1㸦0.5㸧
0
0
0
0
0
࡞࠾ࠊᮏ๣⩌࡟࠾࠸࡚㛫㉁ᛶ⫵⑌ᝈ 3 ౛㸦1.5%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 6 ౛㸦2.9%㸧ࠊ
⚄⤒㞀ᐖ㸦ࢠ࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧28 ౛㸦13.6%㸧ࠊ⫢ᶵ⬟㞀ᐖ 7 ౛㸦3.4%㸧ࠊ⭈ᶵ
⬟㞀ᐖ 4 ౛㸦1.9%㸧ࠊୗᆶయᶵ⬟㞀ᐖ 4 ౛㸦1.9%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ 13 ౛㸦6.3%㸧ࠊ
infusion reaction 15 ౛㸦7.3%㸧ࠊ1 ᆺ⢾ᒀ⑓ 1 ౛㸦0.5%㸧ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ 3 ౛㸦1.5%㸧
ཬࡧࡪ࡝࠺⭷⅖ 1 ౛㸦0.5%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ๪⭈㞀ᐖࠊ⮅⅖ࠊ㔜⑕➽↓ຊ⑕ࠊ⬻
⅖࣭㧊⭷⅖ࠊᚰ➽⅖ࠊ➽⅖ࠊ⫢⅖ࠊᶓ⣠➽⼥ゎ⑕ཬࡧච␿ᛶ⾑ᑠᯈῶᑡᛶ⣸ᩬ⑓ࡣㄆࡵ
ࡽࢀ࡞࠿ࡗࡓࠋ
մᾏእ➨Ϫ┦ヨ㦂㸦CA209037 ヨ㦂㸧2㸧
᭷ᐖ஦㇟ࡣᮏ⸆⩌ 265/268 ౛㸦98.9%㸧
ࠊ໬Ꮫ⒪ἲ⩌ 98/102 ౛㸦96.1%㸧࡟ㄆࡵࡽࢀࠊ἞
㦂⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ஦㇟ࡣᮏ⸆⩌ 199/268 ౛㸦74.3%㸧
ࠊ໬Ꮫ⒪ἲ⩌
85/102 ౛㸦83.3%㸧࡟ㄆࡵࡽࢀࡓࠋ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ
࡜࠾ࡾ࡛࠶ࡗࡓࠋ
࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝
ჾᐁู኱ศ㢮
ᇶᮏㄒ
㸦MedDRA/J ver.17.1㸧
඲๪స⏝
⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ
㈋⾑
౛ᩘ㸦%㸧
ᮏ⸆⩌
໬Ꮫ⒪ἲ⩌
268 ౛
102 ౛
඲ Grade
Grade 3 ௨ୖ
඲ Grade
Grade 3 ௨ୖ
199㸦74.3㸧
33㸦12.3㸧
85㸦83.3㸧
35㸦34.3㸧
18㸦6.7㸧
8
3㸦1.1㸧
24㸦23.5㸧
5㸦4.9㸧
ჾᐁู኱ศ㢮
ᇶᮏㄒ
㸦MedDRA/J ver.17.1㸧
ⓑ⾑⌫ῶᑡ⑕
ዲ୰⌫ῶᑡ⑕
⾑ᑠᯈῶᑡ⑕
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟పୗ⑕
⫶⭠㞀ᐖ
౽⛎
ୗ⑩
ᝏᚰ
჎ྤ
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
↓ຊ⑕
⑂ປ
യᐖࠊ୰ẘ࠾ࡼࡧฎ⨨ྜే⑕
ὀධ࡟క࠺཯ᛂ
⮫ᗋ᳨ᰝ
ALT ቑຍ
AST ቑຍ
ዲ୰⌫ᩘῶᑡ
⾑ᑠᯈᩘῶᑡ
ⓑ⾑⌫ᩘῶᑡ
௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ
㣗ḧῶ㏥
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ
㛵⠇③
➽⫗③
⚄⤒⣔㞀ᐖ
ᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮
㘒ឤぬ
࿧྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ
࿧྾ᅔ㞴
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
⬺ẟ⑕
ࡑ࠺⑛⑕
Ⓨ⑈
ᩬ≧ୣ⑈≧⓶⑈
ᑜᖖᛶⓑᩬ
౛ᩘ㸦%㸧
ᮏ⸆⩌
໬Ꮫ⒪ἲ⩌
268 ౛
102 ౛
඲ Grade
Grade 3 ௨ୖ
඲ Grade
Grade 3 ௨ୖ
0
1㸦0.4㸧
8㸦7.8㸧
2㸦2.0㸧
0
0
20㸦19.6㸧
16㸦15.7㸧
1㸦0.4㸧
1㸦0.4㸧
12㸦11.8㸧
6㸦5.9㸧
18㸦6.7㸧
0
0
0
11㸦4.1㸧
42㸦15.7㸧
33㸦12.3㸧
12㸦4.5㸧
0
1㸦0.4㸧
0
1㸦0.4㸧
15㸦14.7㸧
16㸦15.7㸧
39㸦38.2㸧
21㸦20.6㸧
1㸦1.0㸧
2㸦2.0㸧
2㸦2.0㸧
3㸦2.9㸧
14㸦5.2㸧
82㸦30.6㸧
0
3㸦1.1㸧
7㸦6.9㸧
41㸦40.2㸧
0
4㸦3.9㸧
4㸦1.5㸧
1㸦0.4㸧
9㸦8.8㸧
0
14㸦5.2㸧
15㸦5.6㸧
0
1㸦0.4㸧
3㸦1.1㸧
3㸦1.1㸧
2㸦0.7㸧
0
0
0
1㸦1.0㸧
2㸦2.0㸧
7㸦6.9㸧
8㸦7.8㸧
8㸦7.8㸧
0
0
3㸦2.9㸧
3㸦2.9㸧
2㸦2.0㸧
18㸦6.7㸧
0
17㸦16.7㸧
0
15㸦5.6㸧
11㸦4.1㸧
0
0
13㸦12.7㸧
8㸦7.8㸧
1㸦1.0㸧
0
1㸦0.4㸧
3㸦1.1㸧
0
0
10㸦9.8㸧
10㸦9.8㸧
1㸦1.0㸧
0
13㸦4.9㸧
0
8㸦7.8㸧
0
2㸦0.7㸧
51㸦19.0㸧
34㸦12.7㸧
16㸦6.0㸧
24㸦9.0㸧
0
0
1㸦0.4㸧
0
0
28㸦27.5㸧
2㸦2.0㸧
5㸦4.9㸧
2㸦2.0㸧
0
0
0
0
0
0
࡞࠾ࠊᮏ๣⩌࡟࠾࠸࡚㛫㉁ᛶ⫵⑌ᝈ 8 ౛㸦3.0%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 4 ౛㸦1.5%㸧ࠊ
⚄⤒㞀ᐖ 33 ౛㸦12.3%㸧ࠊ⫢ᶵ⬟㞀ᐖ 22 ౛㸦8.2%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖
➼㸧5 ౛㸦1.9%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ 23 ౛㸦8.6%㸧ࠊ๪⭈㞀ᐖ 1 ౛㸦0.4%㸧ࠊinfusion reaction
10 ౛㸦3.7%㸧ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ 1 ౛㸦0.4%㸧ࠊ⮅⅖ 2 ౛㸦0.7%㸧ཬࡧࡪ࡝࠺⭷⅖ 3 ౛
㸦1.1%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊୗᆶయᶵ⬟㞀ᐖࠊ1 ᆺ⢾ᒀ⑓ࠊ㔜⑕➽↓ຊ⑕ࠊ⬻⅖࣭㧊
⭷⅖ࠊᚰ➽⅖ࠊ➽⅖ࠊ⫢⅖ࠊᶓ⣠➽⼥ゎ⑕ཬࡧච␿ᛶ⾑ᑠᯈῶᑡᛶ⣸ᩬ⑓ࡣㄆࡵࡽࢀ࡞
࠿ࡗࡓࠋ
1㸧Robert C.et al.㸸N.Engl.J.Med.㸪372㸸320㸪2015㸦CA209066 ヨ㦂㸧
2㸧Weber J.S. et al.㸸Lancet Oncol.㸪16㸸375㸪2015㸦CA209037 ヨ㦂㸧㻌㻌
9
4㸬
㸬᪋タ࡟ࡘ࠸࡚
ᢎㄆ᮲௳࡜ࡋ࡚౑⏝ᡂ⦼ㄪᰝ㸦඲౛ㄪᰝ㸧ࡀㄢࡏࡽࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᙜヱㄪᰝࢆ㐺ษ
࡟ᐇ᪋࡛ࡁࡿ᪋タ࡛࠶ࡿᚲせࡀ࠶ࡿࠋࡑࡢୖ࡛ࠊᮏ๣ࡢᢞ୚ࡀ㐺ษ࡞ᝈ⪅ࢆデ᩿࣭≉ᐃ
ࡋࠊᮏ๣ࡢᢞ୚࡟ࡼࡾ㔜⠜࡞๪స⏝ࢆⓎ⌧ࡋࡓ㝿࡟ᑐᛂࡍࡿࡇ࡜ࡀᚲせ࡞ࡓࡵࠊ௨ୗࡢ
ձ㹼ճࡢࡍ࡭࡚ࢆ‶ࡓࡍ᪋タ࡟࠾࠸࡚౑⏝ࡍࡿ࡭ࡁ࡛࠶ࡿࠋ
ձ ᪋タ࡟ࡘ࠸࡚
ձ-1 ୗグࡢ㸦1㸧㹼㸦5㸧ࡢ࠸ࡎࢀ࠿࡟ヱᙜࡍࡿ᪋タ࡛࠶ࡿࡇ࡜ࠋ
(1) ཌ⏕ປാ኱⮧ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔➼㸦㒔㐨ᗓ┴ࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊ
ᆅᇦࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊᆅᇦࡀࢇデ⒪⑓㝔࡞࡝㸧㸦ᖹᡂ 28 ᖺ 10 ᭶ 1 ᪥᫬Ⅼ㸸
427 ᪋タ㸧
(2) ≉ᐃᶵ⬟⑓㝔㸦ᖹᡂ 28 ᖺ 9 ᭶ 1 ᪥᫬Ⅼ㸸84 ᪋タ㸧
(3) 㒔㐨ᗓ┴▱஦ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠ⑓㝔㸦ࡀࢇデ⒪㐃ᦠᣦᐃ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ
༠ຊ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ᥎㐍⑓㝔࡞࡝㸧
(4) እ᮶໬Ꮫ⒪ἲᐊࢆタ⨨ࡋࠊእ᮶໬Ꮫ⒪ἲຍ⟬ 1 ཪࡣእ᮶໬Ꮫ⒪ἲຍ⟬ 2 ࡢ᪋タᇶ‽
࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7 ᭶ 1 ᪥᫬Ⅼ㸸2538 ᪋タ㸧
(5) ᢠᝏᛶ⭘⒆๣ฎ᪉⟶⌮ຍ⟬ࡢ᪋タᇶ‽࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7
᭶ 1 ᪥᫬Ⅼ㸸1284 ᪋タ㸧
ձ-2 ᝏᛶ㯮Ⰽ⭘ࡢ໬Ꮫ⒪ἲཬࡧ๪స⏝Ⓨ⌧᫬ࡢᑐᛂ࡟༑ศ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ
㸦ୗ⾲ࡢ࠸ࡎࢀ࠿࡟ヱᙜࡍࡿ་ᖌ㸧ࡀࠊᙜヱデ⒪⛉ࡢᮏ๣࡟㛵ࡍࡿ἞⒪ࡢ㈐௵⪅࡜ࡋ࡚
㓄⨨ࡉࢀ࡚࠸ࡿࡇ࡜ࠋ
⾲
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 5 ᖺ௨ୖࡢࡀࢇ἞⒪ࡢ⮫ᗋ◊ಟࢆ⾜
ࡗ࡚࠸ࡿࡇ࡜ࠋ࠺ࡕࠊ2 ᖺ௨ୖࡣࠊࡀࢇ⸆≀⒪ἲࢆ୺࡜ࡋࡓ⮫ᗋ⭘⒆Ꮫࡢ◊ಟࢆ⾜
࡞ࡗ࡚࠸ࡿࡇ࡜ࠋ
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 5 ᖺ௨ୖࡢ⓶⭵ᝏᛶ⭘⒆デ⒪ࡢ⮫ᗋ
⤒㦂ࢆ᭷ࡋ࡚࠸ࡿࡇ࡜ࠋ
ղ 㝔ෆࡢ་⸆ရ᝟ሗ⟶⌮ࡢయไ࡟ࡘ࠸࡚
་⸆ရ᝟ሗ⟶⌮࡟ᚑ஦ࡍࡿᑓ௵⪅ࡀ㓄⨨ࡉࢀࠊ〇⸆௻ᴗ࠿ࡽࡢ᝟ሗ❆ཱྀࠊ᭷ຠᛶ࣭Ᏻ඲
ᛶ➼⸆Ꮫⓗ᝟ሗࡢ⟶⌮ཬࡧ་ᖌ➼࡟ᑐࡍࡿ᝟ሗᥦ౪ࠊ᭷ᐖ஦㇟ࡀⓎ⏕ࡋࡓሙྜࡢሗ࿌ᴗ
ົࠊ➼ࡀ㏿ࡸ࠿࡟⾜ࢃࢀࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
10
ճ ๪స⏝ࡢᑐᛂ࡟ࡘ࠸࡚
䐡㻙1 ๪స⏝Ⓨ⌧᫬ࡢᑐᛂయไ࡟㛵ࡍࡿせ௳
㛫㉁ᛶ⫵⑌ᝈ➼ࡢ㔜⠜࡞๪స⏝ࡀⓎ⏕ࡋࡓ㝿࡟ࠊ24 ᫬㛫デ⒪యไࡢୗࠊᙜヱ᪋タཪࡣ
㐃ᦠ᪋タ࡟࠾࠸࡚ࠊⓎ⌧ࡋࡓ๪స⏝࡟ᛂࡌ࡚ධ㝔⟶⌮ཬࡧ CT ➼ࡢ๪స⏝ࡢ㚷ู࡟ᚲせ
࡞᳨ᰝࡢ⤖ᯝࡀᙜ᪥୰࡟ᚓࡽࢀࠊ┤ࡕ࡟ᑐᛂྍ⬟࡞యไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
䐡-2 ་⒪ᚑ஦⪅࡟ࡼࡿ᭷ᐖ஦㇟ᑐᛂ࡟㛵ࡍࡿせ௳
ࡀࢇデ⒪࡟ᦠࢃࡿᑓ㛛ⓗ࡞▱㆑ཬࡧᢏ⬟ࢆ᭷ࡍࡿ་⒪ᚑ஦⪅ࡀ๪స⏝ࣔࢽࢱࣜࣥࢢࢆ
ྵࡵࡓⱞ③ࡢࢫࢡ࣮ࣜࢽࣥࢢࢆ⾜࠸୺἞་࡜᝟ሗࢆඹ᭷࡛ࡁࡿࢳ࣮࣒་⒪యไࡀᩚഛ
ࡉࢀ࡚࠸ࡿࡇ࡜ࠋ࡞࠾ࠊᩚഛయไ࡟ࡘ࠸࡚ࠊࡀࢇᝈ⪅࡜ࡑࡢᐙ᪘࡟༑ศ࡟࿘▱ࡉࢀ࡚࠸
ࡿࡇ࡜ࠋ
䐡-3 ๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚
๪స⏝㸦㛫㉁ᛶ⫵⑌ᝈ࡟ຍ࠼ࠊ㔜⑕➽↓ຊ⑕ࠊᚰ➽⅖ࠊ➽⅖ࠊᶓ⣠➽⼥ゎ⑕ࠊ኱⭠⅖ࠊ
㔜ᗘࡢୗ⑩ࠊ1 ᆺ⢾ᒀ⑓ࠊ⫢ᶵ⬟㞀ᐖࠊ⏥≧⭢ᶵ⬟㞀ᐖࠊ⚄⤒㞀ᐖࠊ⭈㞀ᐖ㸦⭈୙඲࣭
ᒀ⣽⟶㛫㉁ᛶ⭈⅖ࢆྵࡴ㸧
ࠊ๪⭈㞀ᐖࠊ⬻⅖ࠊ㔜ᗘࡢ⓶⭵㞀ᐖࠊ㟼⬦⾑ᰦሰᰦ⑕ࠊinfusion
reactionࠊච␿ᛶ⾑ᑠᯈῶᑡᛶ⣸ᩬ⑓㸦ITP㸧ࠊ㐣ᗘࡢච␿཯ᛂࠊ⬇⫾ඣẘᛶࠊᚰ⮚㞀ᐖ
㸦ᚰᡣ⣽ື࣭ᚎ⬦࣭ᚰᐊᛶᮇእ཰⦰➼㸧ࠊ⁐⾑ᛶ㈋⾑➼㸧࡟ᑐࡋ࡚ࠊᙜヱ᪋タཪࡣ㏆㞄
་⒪ᶵ㛵ࡢᑓ㛛ᛶࢆ᭷ࡍࡿ་ᖌ࡜㐃ᦠࡋ㸦๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚ᣦᑟཬࡧᨭ᥼ࢆ
ཷࡅࡽࢀࡿ᮲௳࡟࠶ࡿࡇ࡜㸧
ࠊ┤ࡕ࡟㐺ษ࡞ฎ⨨ࡀ࡛ࡁࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
㻌
㻌
11
5㸬
㸬ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
࠙Ᏻ඲ᛶࠚ
ձ ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣᮏ๣ࡢᢞ୚ࡀ⚗ᚷ࡜ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᢞ୚ࢆ⾜
ࢃ࡞࠸ࡇ࡜ࠋ
y
ᮏ๣ࡢᡂศ࡟ᑐࡋ㐣ᩄ⑕ࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
ղ ἞⒪๓ࡢホ౯࡟࠾࠸࡚ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢᢞ୚ࡣ᥎ዡࡉࢀ࡞࠸
ࡀࠊ௚ࡢ἞⒪㑅ᢥ⫥ࡀ࡞࠸ሙྜ࡟㝈ࡾࠊៅ㔜࡟ᮏ๣ࢆ౑⏝ࡍࡿࡇ࡜ࢆ⪃៖࡛ࡁࡿࠋ
y
㛫㉁ᛶ⫵⑌ᝈࡢྜేཪࡣ᪤ ࡢ࠶ࡿᝈ⪅
y
⬚㒊⏬ീ᳨ᰝ࡛㛫㉁ᙳࢆㄆࡵࡿᝈ⪅ཬࡧάືᛶࡢᨺᑕ⥺⫵⮚⅖ࡸឤᰁᛶ⫵⅖
➼ࡢ⫵࡟⅖⑕ᛶኚ໬ࡀࡳࡽࢀࡿᝈ⪅
y
⮬ᕫච␿⑌ᝈࡢྜేࠊཪࡣ៏ᛶⓗ࡞ⱝࡋࡃࡣ෌Ⓨᛶࡢ⮬ᕫච␿⑌ᝈࡢ᪤ Ṕࡢ
࠶ࡿᝈ⪅
y
ECOG Performance Status 3-4㸦ὀ1㸧ࡢᝈ⪅
࠙᭷ຠᛶࠚ
ձ ໬Ꮫ⒪ἲṔࡢ࡞࠸ᝈ⪅ཬࡧ໬Ꮫ⒪ἲṔࡢ࠶ࡿᝈ⪅࡟࠾࠸࡚ᮏ๣ࡢ᭷ຠᛶࡀ♧ࡉࢀ
࡚࠸ࡿࠋ
࡞࠾ࠊBRAF㑇ఏᏊኚ␗ࢆ᭷ࡍࡿᝈ⪅࡟࠾࠸࡚ࡣࠊBRAF㜼ᐖ๣࡟ࡼࡿ἞⒪ࡶ⪃៖ࡍ
ࡿࡇ࡜ࠋ
ղ ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ᑐࡍࡿᮏ๣ࡢᢞ୚ཬࡧ౑⏝᪉ἲ࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢ᭷ຠᛶࡀ
☜❧ࡉࢀ࡚࠾ࡽࡎࠊᮏ๣ࡢᢞ୚ᑐ㇟࡜࡞ࡽ࡞࠸ࠋ
y
⾡ᚋ⿵ຓ໬Ꮫ⒪ἲࠋ
y
௚ࡢᢠᝏᛶ⭘⒆๣࡜ࡢే⏝ࠋ
㸦ὀ1㸧
Score
0
1
2
3
4
ECOG ࡢ Performance Status㸦PS㸧
ᐃ⩏
඲ࡃၥ㢟࡞ࡃάື࡛ࡁࡿࠋⓎ⑓๓࡜ྠࡌ᪥ᖖ⏕άࡀไ㝈࡞ࡃ⾜࠼ࡿࠋ
⫗యⓗ࡟⃭ࡋ࠸άືࡣไ㝈ࡉࢀࡿࡀࠊṌ⾜ྍ⬟࡛ࠊ㍍సᴗࡸᗙࡗ࡚ࡢసᴗࡣ⾜࠺ࡇ࡜ࡀ࡛ࡁࡿࠋ
౛㸸㍍࠸ᐙ஦ࠊ஦ົసᴗ
Ṍ⾜ྍ⬟࡛⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣࡍ࡭࡚ྍ⬟ࡔࡀసᴗࡣ࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࡣ࣋ࢵࢻእ࡛
㐣ࡈࡍࠋ
㝈ࡽࢀࡓ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡋ࠿࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࢆ࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
඲ࡃືࡅ࡞࠸ࠋ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣ඲ࡃ࡛ࡁ࡞࠸ࠋ᏶඲࡟࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
12
6㸬
㸬ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
ձ ῧ௜ᩥ᭩➼࡟ຍ࠼ࠊ〇㐀㈍኎ᴗ⪅ࡀᥦ౪ࡍࡿ㈨ᩱ➼࡟ᇶ࡙ࡁᮏ๣ࡢ≉ᛶཬࡧ㐺ṇ౑
⏝ࡢࡓࡵ࡟ᚲせ࡞᝟ሗࢆ༑ศ࡟⌮ゎࡋ࡚࠿ࡽ౑⏝ࡍࡿࡇ࡜ࠋ
ղ ἞⒪㛤ጞ࡟ඛ❧ࡕࠊᝈ⪅ཪࡣࡑࡢᐙ᪘࡟᭷ຠᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋࠊྠពࢆᚓ
࡚࠿ࡽᢞ୚ࡍࡿࡇ࡜ࠋ
ճ ୺࡞๪స⏝ࡢ࣐ࢿࢪ࣓ࣥࢺ࡟ࡘ࠸࡚
y
㛫㉁ᛶ⫵⑌ᝈࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚࡟࠶ࡓࡗ࡚ࡣࠊ⮫ᗋ⑕
≧㸦࿧྾ᅔ㞴ࠊတႿࠊⓎ⇕➼㸧ࡢ☜ㄆཬࡧ⬚㒊 X ⥺᳨ᰝࡢᐇ᪋➼ࠊほᐹࢆ༑ศ
࡟⾜࠺ࡇ࡜ࠋࡲࡓࠊᚲせ࡟ᛂࡌ࡚⬚㒊 CTࠊ⾑Ύ࣐࣮࣮࢝➼ࡢ᳨ᰝࢆᐇ᪋ࡍࡿ
ࡇ࡜ࠋ
y
ᮏ๣ࡢᢞ୚ࡣ㔜ᗘࡢ infusion reaction ࡟ഛ࠼࡚⥭ᛴ᫬࡟༑ศ࡞ᑐᛂࡢ࡛ࡁࡿ‽
ഛࢆ⾜ࡗࡓୖ࡛㛤ጞࡍࡿࡇ࡜ࠋࡲࡓࠊ2 ᅇ┠௨㝆ࡢᮏ๣ᢞ୚᫬࡟ infusion reaction
ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡶ࠶ࡿࡢ࡛ࠊᮏ๣ᢞ୚୰ཬࡧᮏ๣ᢞ୚⤊஢ᚋࡣࣂ࢖ࢱࣝࢧ࢖
ࣥࢆ ᐃࡍࡿ➼ࠊᝈ⪅ࡢ≧ែࢆ༑ศ࡟ほᐹࡍࡿࡇ࡜ࠋ࡞࠾ࠊinfusion reaction ࢆ
Ⓨ⌧ࡋࡓሙྜ࡟ࡣࠊ඲࡚ࡢᚩೃཬࡧ⑕≧ࡀ᏶඲࡟ᅇ᚟ࡍࡿࡲ࡛ᝈ⪅ࢆ༑ศほᐹ
ࡍࡿࡇ࡜ࠋ
y
⏥≧⭢ᶵ⬟㞀ᐖࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚㛤ጞ๓ཬࡧᢞ୚ᮇ㛫
୰ࡣᐃᮇⓗ࡟⏥≧⭢ᶵ⬟᳨ᰝ㸦TSHࠊ㐟㞳 T3ࠊ㐟㞳 T4 ➼ࡢ ᐃ㸧ࢆᐇ᪋ࡍࡿ
ࡇ࡜ࠋ
y
ᮏ๣ࡢᢞ୚࡟ࡼࡾࠊ㐣ᗘࡢච␿཯ᛂ࡟㉳ᅉࡍࡿ࡜⪃࠼ࡽࢀࡿᵝࠎ࡞⑌ᝈࡸ⑓ែ
ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࠋ␗ᖖࡀㄆࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓ
ᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿
཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊᮏ๣ࡢఇ⸆ཪࡣ୰Ṇࠊཬࡧ๪⭈⓶㉁࣍
ࣝࣔࣥ๣ࡢᢞ୚➼ࢆ⪃៖ࡍࡿࡇ࡜ࠋ࡞࠾ࠊ๪⭈⓶㉁࣍ࣝࣔࣥࡢᢞ୚࡟ࡼࡾ๪స
⏝ࡢᨵၿࡀㄆࡵࡽࢀ࡞࠸ሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝࣔࣥ௨እࡢච␿ᢚไ๣ࡢ㏣ຍ
ࡶ⪃៖ࡍࡿࡇ࡜ࠋ
y
ᢞ୚⤊஢ᚋࠊᩘ㐌㛫࠿ࡽᩘ࢝᭶⤒㐣ࡋ࡚࠿ࡽ๪స⏝ࡀⓎ⌧ࡍࡿࡇ࡜ࡀ࠶ࡿࡓࡵࠊ
ᮏ๣ࡢᢞ୚⤊஢ᚋ࡟ࡶ๪స⏝ࡢⓎ⌧࡟༑ศ࡟ὀពࡍࡿࡇ࡜ࠋ
y
1 ᆺ⢾ᒀ⑓㸦๻⑕ 1 ᆺ⢾ᒀ⑓ࢆྵࡴ㸧ࡀ࠶ࡽࢃࢀࠊ⢾ᒀ⑓ᛶࢣࢺ࢔ࢩࢻ࣮ࢩࢫ
࡟⮳ࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊཱྀῬࠊᝏᚰࠊ჎ྤ➼ࡢ⑕≧ࡢⓎ⌧ࡸ⾑⢾್ࡢୖ᪼࡟༑
ศὀពࡍࡿࡇ࡜ࠋ1 ᆺ⢾ᒀ⑓ࡀ␲ࢃࢀࡓሙྜ࡟ࡣᢞ୚ࢆ୰Ṇࡋࠊ࢖ࣥࢫࣜࣥ〇
๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇ࡜ࠋ
մ ᮏ๣ࡢ⮫ᗋヨ㦂࡟࠾࠸࡚ࠊᢞ୚㛤ጞ࠿ࡽ 3 ࣨ᭶௨ෆࠊࡑࢀ௨㝆ࡣࠊᢞ୚㛤ጞ࠿ࡽ 1
ᖺ㛫ࡣ 6 㐌㛫ࡈ࡜࡟᭷ຠᛶࡢホ౯ࢆ⾜ࡗ࡚࠸ࡓࡇ࡜ࢆཧ⪃࡟ࠊᮏ๣ᢞ୚୰ࡣᐃᮇⓗ
࡟ຠᯝࡢ☜ㄆࢆ⾜࠺ࡇ࡜ࠋ
13
ูῧ㸱
᭱㐺౑⏝᥎㐍࢞࢖ࢻࣛ࢖ࣥ
࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧
㸦㈍኎ྡ㸸࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 20 mgࠊ࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 100 mg㸧
㹼㠀ᑠ⣽⬊⫵⒴㹼
ᖹᡂ㸰㸷ᖺ㸰᭶
ཌ⏕ປാ┬
┠ḟ
1.
2.
3.
4.
5.
6.
ࡣࡌࡵ࡟
ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
⮫ᗋᡂ⦼
᪋タ࡟ࡘ࠸࡚
ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
P2
P3
P4
P9
P11
P13
1
1. ࡣࡌࡵ࡟
་⸆ရࡢ᭷ຠᛶ࣭Ᏻ඲ᛶࡢ☜ಖࡢࡓࡵ࡟ࡣࠊῧ௜ᩥ᭩➼࡟ᇶ࡙࠸ࡓ㐺ṇ࡞౑⏝ࡀồࡵ
ࡽࢀࡿࠋࡉࡽ࡟ࠊ㏆ᖺࡢ⛉Ꮫᢏ⾡ࡢ㐍Ṍ࡟ࡼࡾࠊᢠయ་⸆ရ࡞࡝ࡢ㠉᪂ⓗ࡞᪂つస⏝ᶵ
ᗎ་⸆ရࡀᢎㄆࡉࢀࡿ୰࡛ࠊࡇࢀࡽࡢ་⸆ရࢆ┿࡟ᚲせ࡞ᝈ⪅࡟ᥦ౪ࡍࡿࡇ࡜ࡀႚ⥭ࡢ
ㄢ㢟࡜࡞ࡗ࡚࠾ࡾࠊ
⤒῭㈈ᨻ㐠Ⴀ࡜ᨵ㠉ࡢᇶᮏ᪉㔪 2016
㸦ᖹᡂ 28 ᖺ㸴᭶㸰᪥㛶㆟Ỵᐃ㸧
࡟࠾࠸࡚ࡶࠊ㠉᪂ⓗ་⸆ရ➼ࡢ౑⏝ࡢ᭱㐺໬᥎㐍ࢆᅗࡿࡇ࡜࡜ࡉࢀ࡚࠸ࡿࠋ
᪂つస⏝ᶵᗎ་⸆ရࡣࠊ⸆⌮స⏝ࡸᏳ඲ᛶࣉࣟࣇ࢓࢖ࣝࡀ᪤Ꮡࡢ་⸆ရ࡜᫂ࡽ࠿࡟␗
࡞ࡿࡇ࡜ࡀ࠶ࡿࠋࡇࡢࡓࡵࠊ᭷ຠᛶཬࡧᏳ඲ᛶ࡟㛵ࡍࡿ᝟ሗࡀ༑ศ⵳✚ࡍࡿࡲ࡛ࡢ㛫ࠊ
ᙜヱ་⸆ရࡢᜠᜨࢆᙉࡃཷࡅࡿࡇ࡜ࡀᮇᚅࡉࢀࡿᝈ⪅࡟ᑐࡋ࡚౑⏝ࡍࡿ࡜࡜ࡶ࡟ࠊ๪స
⏝ࡀⓎ⌧ࡋࡓ㝿࡟ᚲせ࡞ᑐᛂࢆ࡜ࡿࡇ࡜ࡀྍ⬟࡞୍ᐃࡢせ௳ࢆ‶ࡓࡍ་⒪ᶵ㛵࡛౑⏝
ࡍࡿࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ
ࡋࡓࡀࡗ࡚ࠊᮏ࢞࢖ࢻࣛ࢖࡛ࣥࡣࠊ㛤Ⓨẁ㝵ࡸࡇࢀࡲ࡛࡟ᚓࡽࢀ࡚࠸ࡿ་Ꮫ⸆Ꮫⓗ࣭
⛉Ꮫⓗぢᆅ࡟ᇶ࡙ࡁࠊ௨ୗࡢ་⸆ရࡢ᭱㐺࡞౑⏝ࢆ᥎㐍ࡍࡿほⅬ࠿ࡽᚲせ࡞せ௳ࠊ⪃࠼
᪉ཬࡧ␃ព஦㡯ࢆ♧ࡍࠋ
࡞࠾ࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ⊂❧⾜ᨻἲே་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓࠊබ┈♫ᅋἲே᪥ᮏ
⮫ᗋ⭘⒆Ꮫ఍ࠊ୍⯡♫ᅋἲே᪥ᮏ⮫ᗋෆ⛉་఍ࠊ≉ᐃ㠀Ⴀ฼άືἲே᪥ᮏ⫵⒴Ꮫ఍ཬࡧ
୍⯡♫ᅋἲே᪥ᮏ࿧྾ჾᏛ఍ࡢ༠ຊࡢࡶ࡜సᡂࡋࡓࠋ
ᑐ㇟࡜࡞ࡿ་⸆ရ㸸࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 20 mgࠊ࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 100 mg㸦୍
⯡ྡ㸸࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧
㸧
ᑐ㇟࡜࡞ࡿຠ⬟ཪࡣຠᯝ㸸PD-L1 㝧ᛶࡢษ㝖୙⬟࡞㐍⾜࣭෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴
ᑐ㇟࡜࡞ࡿ⏝ἲཬࡧ⏝㔞㸸㏻ᖖࠊᡂே࡟ࡣࠊ࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧࡜ࡋ࡚ࠊ1
ᅇ 200mg ࢆ 3 㐌㛫㛫㝸࡛ 30 ศ㛫࠿ࡅ࡚Ⅼ⁲㟼ὀࡍࡿࠋ
〇㐀㈍ ኎ ᴗ ⪅㸸MSD ᰴᘧ఍♫
2
2㸬
㸬ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 20 mg ཬࡧ 100 mg㸦୍⯡ྡ㸸࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮
࠼㸧
ࠊ௨ୗࠕᮏ๣ࠖ࡜࠸࠺ࠋ㸧ࡣࠊPD-1㸦programmed cell death-1㸧࡜ࡑࡢࣜ࢞ࣥࢻ࡛࠶
ࡿ PD-L1 ཬࡧ PD-L2 ࡜ࡢ⤖ྜࢆ┤᥋㜼ᐖࡍࡿࠊ
ࣄࢺ໬ IgG4 ࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡿࠋ
PD-1 ⤒㊰ࡣ T ⣽⬊ච␿┘どᶵᵓ࠿ࡽ㏨ࢀࡿࡓࡵ࡟ࡀࢇ⣽⬊ࡀ฼⏝ࡍࡿ୺࡞ච␿ไᚚ
ࢫ࢖ࢵࢳ࡛ࠊPD-1 ࡣࠊ೺ᗣ࡞≧ែ࡟࠾࠸࡚άᛶᆺ T ⣽⬊ࡢ⣽⬊⾲㠃࡟Ⓨ⌧ࡋࠊ⮬ᕫච
␿཯ᛂࢆྵࡴ୙ᚲせཪࡣ㐣๫࡞ච␿཯ᛂࢆไᚚࡍࡿࠋࡍ࡞ࢃࡕࠊPD-1 ࡣࣜ࢞ࣥࢻ࡜⤖
ྜࡍࡿࡇ࡜࡟ࡼࡾᢠཎཷᐜయ࡟ࡼࡿࢩࢢࢼࣝఏ㐩ࢆ㈇࡟ไᚚࡍࡿཷᐜయ࡛࠶ࡿࠋPD-L1
ࡢṇᖖ⤌⧊࡟࠾ࡅࡿⓎ⌧ࡣࢃࡎ࠿࡛࠶ࡿࡀࠊከࡃࡢࡀࢇ⣽⬊࡛ࡣ T ⣽⬊ࡢാࡁࢆᢚ࠼ࡿ
࡯࡝㐣๫࡟Ⓨ⌧ࡋ࡚࠸ࡿࠋࡀࢇ⣽⬊࡟࠾ࡅࡿ PD-L1 ࡢ㧗Ⓨ⌧ࡣࠊ⭈⣽⬊⒴ࠊ⮅⮚⒴ࠊ
⫢⣽⬊⒴ࠊ༸ᕢ⒴ࠊ㠀ᑠ⣽⬊⫵⒴࡞࡝ࡢᵝࠎ࡞ࡀࢇ࡛ணᚋ୙ⰋᅉᏊ࡛࠶ࡾࠊప࠸⏕Ꮡ⋡
࡜ࡢ┦㛵ᛶࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ
」ᩘࡢࡀࢇࡢ⮫ᗋⓗணᚋ࡜ PD-L1 Ⓨ⌧ࡢ┦㛵ᛶ࠿ࡽࠊPD-1 ࡜ PD-L1 ࡢ⤒㊰ࡣ⭘⒆ࡢ
ච␿ᅇ㑊࡟࠾࠸࡚㔜せ࡞ᙺ๭ࢆᢸ࠺ࡇ࡜ࡀ♧၀ࡉࢀ࡚࠾ࡾࠊ᪂ࡓ࡞ࡀࢇ἞⒪ࡢᶆⓗ࡜ࡋ
࡚ᮇᚅࡉࢀ࡚࠸ࡿࠋ
ᮏ๣ࡣࠊPD-1 ࡜ PD-L1 ཬࡧ PD-L2 ࡢ୧ࣜ࢞ࣥࢻࡢ⤖ྜࢆ㜼ᐖࡍࡿࡇ࡜࡟ࡼࡾࠊ⭘⒆
ᚤᑠ⎔ቃ୰ࡢ⭘⒆≉␗ⓗ⣽⬊യᐖᛶ T ࣜࣥࣃ⌫ࢆάᛶ໬ࡉࡏࠊᢠ⭘⒆ච␿ࢆ෌άᛶ໬ࡍ
ࡿࡇ࡜࡛ᢠ⭘⒆ຠᯝࢆⓎ᥹ࡍࡿࠋ
ᮏ๣ࡢస⏝ᶵᗎ࡟ᇶ࡙ࡃ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝➼ࡀ࠶ࡽࢃࢀࠊ㔜⠜ཪࡣṚஸ࡟
⮳ࡿྍ⬟ᛶࡀ࠶ࡿࠋᮏ๣ࡢᢞ୚୰ཬࡧᢞ୚ᚋ࡟ࡣࠊᝈ⪅ࡢほᐹࢆ༑ศ࡟⾜࠸ࠊ␗ᖖࡀㄆ
ࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺
ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝ
ࣔࣥ๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ᚲせࡀ࠶ࡿࠋ
3
3㸬
㸬⮫ᗋᡂ⦼
PD-L1 㝧ᛶࡢษ㝖୙⬟࡞㐍⾜࣭෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴ࡢᢎㄆ᫬࡟ホ౯ࢆ⾜ࡗࡓ୺࡞⮫ᗋヨ
㦂ࡢᡂ⦼ࢆ♧ࡍࠋ
࠙᭷ຠᛶࠚ
ձᅜ㝿ඹྠ➨Ϫ┦ヨ㦂㸦KEYNOTE-024 ヨ㦂㸧
໬Ꮫ⒪ἲṔࡢ࡞࠸ࠊEGFR 㑇ఏᏊኚ␗㝜ᛶࠊALK ⼥ྜ㑇ఏᏊ㝜ᛶཬࡧ PD-L1 㝧ᛶ㸦PD-L1
ࢆⓎ⌧ࡋࡓ⭘⒆⣽⬊ࡀ༨ࡵࡿ๭ྜ㸦௨ୗࠕTPSࠖ࡜࠸࠺ࠋ
㸧Ӎ50%㸧*ࡢษ㝖୙⬟࡞㐍⾜࣭
෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴ᝈ⪅㸦305 ౛ࠊ᪥ᮏே 40 ౛ࢆྵࡴ㸧ࢆᑐ㇟࡟ࠊᮏ๣ 200 mg 3 㐌㛫
㛫㝸ᢞ୚ࡢ᭷ຠᛶཬࡧᏳ඲ᛶࡀࠊࣉࣛࢳࢼ〇๣ࢆྵࡴᶆ‽ⓗ໬Ꮫ⒪ἲ㸦௨ୗࠕSOCࠖ࡜
࠸࠺ࠋ㸧ࢆᑐ↷࡜ࡋ᳨࡚ウࡉࢀࡓࠋ࡞࠾ࠊ⏬ീホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡓሙྜ࡟ࠊ⑌
ᝈ㐍⾜ࢆ♧ࡍ⑕≧ࡀㄆࡵࡽࢀ࡞࠸➼ࡢ⮫ᗋⓗ࡟Ᏻᐃࡋ࡚࠸ࡿᝈ⪅࡛ࡣࠊḟᅇ௨㝆ࡢ⏬ീ
ホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡿࡲ࡛ᮏ๣ࡢᢞ୚ࢆ⥅⥆ࡍࡿࡇ࡜ࡀྍ⬟࡜ࡉࢀࡓࠋ୺せホ౯
㡯┠ࡣ↓ቑᝏ⏕Ꮡᮇ㛫㸦௨ୗࠕPFSࠖ࡜࠸࠺ࠋ㸧
ࠊ๪ḟホ౯㡯┠ࡣ඲⏕Ꮡᮇ㛫㸦௨ୗࠕOSࠖ
࡜࠸࠺ࠋ
㸧࡜ࡉࢀࠊᮏ๣ࡣࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲ࡜ẚ㍑ࡋ࡚ࠊPFSࠊཬࡧ OS㸦୰
㛫ゎᯒ㸧ࢆ᭷ព࡟ᘏ㛗ࡋࡓࠋ
*㸸ࢥࣥࣃࢽ࢜ࣥデ᩿⸆࡜ࡋ࡚〇㐀㈍኎ᢎㄆࡉࢀ࡚࠸ࡿ PD-L1 IHC 22C3 pharmDxࠕࢲࢥࠖࢆ⏝࠸᳨࡚
ᰝࡉࢀࡓࠋ
୰ኸุᐃ࡟ࡼࡿPFSࡢ᭱⤊ゎᯒ᫬ࡢKaplan-Meier᭤⥺㸦PD-L1㝧ᛶ㸦Ӎ50%㸧ࡢᝈ⪅㞟ᅋ㸧
4
OSࡢ
ࡢ୰㛫ゎᯒ᫬ࡢKaplan-Meier᭤⥺㸦PD-L1㝧ᛶ㸦Ӎ50%㸧ࡢᝈ⪅㞟ᅋ㸧
ղᅜ㝿ඹྠ➨ϩϪ┦ヨ㦂㸦KEYNOTE-010 ヨ㦂㸧
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔ*1 ࢆ᭷ࡍࡿ PD-L1 㝧ᛶ㸦TPSӍ1%㸧*2 ࡢษ㝖୙⬟࡞㐍⾜࣭
෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴ᝈ⪅㸦1,033 ౛ࠊ᪥ᮏே 91 ౛ࢆྵࡴ㸧ࢆᑐ㇟࡟ࠊᮏ๣ 2 mg/kg 3 㐌
㛫㛫㝸ᢞ୚ཬࡧ 10 mg/kg 3 㐌㛫㛫㝸ᢞ୚ࡢ᭷ຠᛶཬࡧᏳ඲ᛶࡀࠊࢻࢭࢱ࢟ࢭࣝỈ࿴≀
㸦௨ୗࠕDOCࠖ࡜࠸࠺ࠋ
㸧ࢆᑐ↷࡜ࡋ᳨࡚ウࡉࢀࡓࠋ࡞࠾ࠊ⏬ീホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵ
ࡽࢀࡓሙྜ࡟ࠊ⑌ᝈ㐍⾜ࢆ♧ࡍ⑕≧ࡀㄆࡵࡽࢀ࡞࠸➼ࡢ⮫ᗋⓗ࡟Ᏻᐃࡋ࡚࠸ࡿᝈ⪅࡛ࡣࠊ
ḟᅇ௨㝆ࡢ⏬ീホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡿࡲ࡛ᮏ๣ࡢᢞ୚⥅⥆ࢆྍ⬟࡜ࡉࢀࡓࠋ୺せ
ホ౯㡯┠ࡣ OS ཬࡧ PFS ࡜ࡉࢀࠊᮏ๣ࡣ DOC ࡜ẚ㍑ࡋ࡚ࠊOS ࢆ᭷ព࡟ᘏ㛗ࡋࡓࠋ
*1㸸EGFR 㑇ఏᏊኚ␗㝧ᛶཪࡣ ALK ⼥ྜ㑇ఏᏊ㝧ᛶࡢᝈ⪅࡛ࡣࠊࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲ࡟ࡼࡿ
἞⒪Ṕ࡟ຍ࠼ࠊࡑࢀࡒࢀ EGFR 㜼ᐖస⏝ཪࡣ ALK 㜼ᐖస⏝ࢆ᭷ࡍࡿᢠᝏᛶ⭘⒆๣࡟ࡼࡿ἞⒪Ṕ
ࢆ᭷ࡍࡿᝈ⪅ࡀ⤌ࡳධࢀࡽࢀࡓࠋ
*2㸸PD-L1 IHC 22C3 pharmDxࠕࢲࢥࠖࡢヨస࢟ࢵࢺࢆ⏝࠸᳨࡚ᰝࡉࢀࡓࠋ
5
OS ࡢ᭱⤊ゎᯒ᫬ࡢ Kaplan-Meier ᭤⥺㸦PD-L1 㝧ᛶ㸦Ӎ1%㸧ࡢᝈ⪅㞟ᅋ㸧
࠙Ᏻ඲ᛶࠚ
䐟ᅜ㝿ඹྠ➨䊢┦ヨ㦂䠄KEYNOTE-024 ヨ㦂䠅
᭷ᐖ஦㇟ࡣᮏ๣⩌ 148/154 ౛㸦96.1%㸧ཬࡧ SOC ⩌ 145/150 ౛㸦96.7%㸧࡟ㄆࡵࡽࢀࠊ
἞㦂⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ஦㇟ࡣࠊࡑࢀࡒࢀ 113/154 ౛㸦73.4%㸧ཬࡧ
135/150 ౛㸦90.0%㸧࡟ㄆࡵࡽࢀࡓࠋ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ
࡜࠾ࡾ࡛࠶ࡗࡓࠋ
࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝㸦Ᏻ඲ᛶゎᯒᑐ㇟㞟ᅋ㸧
SOC
PT
㸦MedDRA ver.19.0㸧
౛ᩘ㸦%㸧
ᮏ๣⩌
154౛
඲ Grade
඲๪స⏝
113
(73.4)
⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ
㈋⾑
8
(5.2)
ⓑ⾑⌫ῶᑡ⑕
1
(0.6)
ዲ୰⌫ῶᑡ⑕
1
(0.6)
⾑ᑠᯈῶᑡ⑕
0
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟ஹ㐍⑕
11
(7.1)
⏥≧⭢ᶵ⬟పୗ⑕
12
(7.8)
⫶⭠㞀ᐖ
౽⛎
6
(3.9)
ୗ⑩
22
(14.3)
ᝏᚰ
15
(9.7)
ཱྀෆ⅖
4
(2.6)
SOC ⩌
150౛
Grade 3௨ୖ
41
(26.6)
඲ Grade
135
(90.0)
Grade 3௨ୖ
80
(53.3)
3
0
0
0
66
8
34
17
29
2
20
8
0
0
1
(0.7)
17
20
65
18
(11.3)
(13.3)
(43.3)
(12.0)
(1.9)
0
0
6
(3.9)
0
0
6
(44.0)
(5.3)
(22.7)
(11.3)
(19.3)
(1.3)
(13.3)
(5.3)
0
0
0
2
3
2
(1.3)
(2.0)
(1.3)
჎ྤ
4
(2.6)
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
↓ຊ⑕
5
(3.2)
⑂ປ
16
(10.4)
೏ᛰឤ
1
(0.6)
Ⓨ⇕
16
(10.4)
⮫ᗋ᳨ᰝ
࢔ࣛࢽࣥ࢔࣑ࣀࢺ
10
(6.5)
ࣛࣥࢫࣇ࢙࣮ࣛࢮ
ቑຍ
࢔ࢫࣃࣛࢠࣥ㓟࢔
8
(5.2)
࣑ࣀࢺࣛࣥࢫࣇ࢙
࣮ࣛࢮቑຍ
⾑୰ࢡࣞ࢔ࢳࢽࣥ
3
(1.9)
ቑຍ
ዲ୰⌫ᩘῶᑡ
0
⾑ᑠᯈᩘῶᑡ
0
ⓑ⾑⌫ᩘῶᑡ
1
(0.6)
௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ
㣗ḧῶ㏥
14
(9.1)
ప࣐ࢢࢿࢩ࣒࢘⾑
1
(0.6)
⑕
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ
㛵⠇③
13
(8.4)
⚄⤒⣔㞀ᐖ
࿡ぬ␗ᖖ
1
(0.6)
ᮎᲈᛶࢽ࣮ࣗࣟࣃ
2
(1.3)
ࢳ࣮
࿧྾ჾࠊ⬚㒌࠾ࡼࡧ⦪㝸㞀ᐖ
⫵⮚⅖
8
(5.2)
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
⬺ẟ⑕
0
⓶⭵஝⇱
8
(5.2)
ࡑ࠺⑛⑕
12
(7.8)
Ⓨ⑈
11
(7.1)
1
(0.6)
30
(20.0)
1
(0.7)
1
2
(0.6)
(1.3)
(7.3)
(28.7)
(6.0)
(5.3)
2
5
(1.3)
(3.3)
0
0
11
43
9
8
0
7
(4.7)
0
5
(3.3)
0
0
15
(10.0)
1
(0.7)
0
0
0
20
18
16
(13.3)
(12.0)
(10.7)
6
9
3
(4.0)
(6.0)
(2.0)
0
0
39
9
(26.0)
(6.0)
4
0
4
(2.7)
0
0
15
9
(10.0)
(6.0)
1
(0.7)
(2.6)
1
(0.7)
1
(0.7)
(0.6)
12
1
3
3
(8.0)
(0.7)
(2.0)
(2.0)
2
(1.3)
4
0
0
0
1
0
0
(2.7)
0
0
0
0
0
0
0
࡞࠾ࠊᮏ๣⩌࡛㛫㉁ᛶ⫵⑌ᝈࡣ 9 ౛㸦5.8%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ࡣ 8 ౛㸦5.2%㸧ࠊ
⚄⤒㞀ᐖ㸦ࢠ࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧ࡣ 2 ౛㸦1.3%㸧ࠊ⫢ᶵ⬟㞀ᐖࡣ 22 ౛㸦14.3%㸧ࠊ
⏥≧⭢ᶵ⬟㞀ᐖࡣ 21 ౛㸦13.6%㸧ࠊୗᆶయᶵ⬟㞀ᐖࡣ 1 ౛㸦0.6%㸧ࠊ1 ᆺ⢾ᒀ⑓ࡣ 1 ౛
㸦0.6%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧ࡣ 1 ౛㸦0.6%㸧ࠊ⮅⅖ࡣ 1 ౛㸦0.6%㸧ࠊ
➽⅖࣭ᶓ⣠➽⼥ゎ⑕ࡣ 1 ౛㸦0.6%㸧ཬࡧ infusion reaction ࡣ 5 ౛㸦3.2%㸧࡛ㄆࡵࡽࢀࡓࠋ
ࡲࡓࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࠊ๪⭈ᶵ⬟㞀ᐖࠊ
㔜⑕➽↓ຊ⑕ࠊ⬻⅖࣭㧊⭷⅖ࠊࡪ࡝࠺⭷⅖ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
䐠ᅜ㝿ඹྠ➨ϩ/Ϫ┦ヨ㦂㸦KEYNOTE-010 ヨ㦂㸧
᭷ᐖ஦㇟ࡣ 2 mg/kg Q3W ⩌ 331/339 ౛㸦97.6%㸧ࠊ10 mg/kg Q3W ⩌ 330/343 ౛㸦96.2%㸧
ཬࡧ DOC ⩌ 297/309 ౛㸦96.1%㸧࡟ㄆࡵࡽࢀࠊ἞㦂⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ
஦㇟ࡣࠊࡑࢀࡒࢀ 215/339 ౛㸦63.4%㸧ࠊ226/343 ౛㸦65.9%㸧ཬࡧ 251/309 ౛㸦81.2%㸧
࡟ㄆࡵࡽࢀࡓࠋ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ࡜࠾ࡾ࡛࠶ࡗࡓࠋ
7
࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝㸦Ᏻ඲ᛶゎᯒᑐ㇟㞟ᅋ㸧
SOC
౛ᩘ㸦%㸧
PT
2 mg/kg Q3W ⩌
10 mg/kg Q3W ⩌
DOC ⩌
㸦MedDRA ver.18.0㸧
339౛
343౛
309౛
඲ Grade Grade 3௨ୖ ඲ Grade Grade 3௨ୖ ඲ Grade Grade 3௨ୖ
඲๪స⏝
215 (63.4) 43 (12.7) 226 (65.9) 55 (16.0) 251 (81.2) 109 (35.3)
⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ
㈋⾑
10 (2.9)
3
(0.9) 14 (4.1)
1
(0.3) 40 (12.9) 5
(1.6)
ዲ୰⌫ῶᑡ⑕
1
(0.3)
0
1
(0.3)
0
44 (14.2) 38 (12.3)
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟పୗ⑕
25 (7.4)
0
23 (6.7)
0
1
(0.3)
0
⫶⭠㞀ᐖ
ୗ⑩
24 (7.1)
2
(0.6) 22 (6.4)
0
56 (18.1) 7
(2.3)
ᝏᚰ
37 (10.9) 1
(0.3) 31 (9.0)
2
(0.6) 45 (14.6) 1
(0.3)
ཱྀෆ⅖
13 (3.8)
0
7
(2.0)
1
(0.3) 43 (13.9) 3
(1.0)
჎ྤ
12 (3.5)
0
13 (3.8)
1
(0.3) 24 (7.8)
2
(0.6)
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
↓ຊ⑕
20 (5.9)
1
(0.3) 19 (5.5)
2
(0.6) 35 (11.3) 6
(1.9)
⑂ປ
46 (13.6) 4
(1.2) 49 (14.3) 6
(1.7) 76 (24.6) 11 (3.6)
ᮎᲈᛶᾋ⭘
5
(1.5)
0
4
(1.2)
0
21 (6.8)
0
Ⓨ⇕
10 (2.9)
1
(0.3) 14 (4.1)
0
17 (5.5)
1
(0.3)
⮫ᗋ᳨ᰝ
ዲ୰⌫ᩘῶᑡ
0
0
2
(0.6)
0
24 (7.8) 19 (6.1)
ⓑ⾑⌫ᩘῶᑡ
0
0
3
(0.9)
0
16 (5.2) 10 (3.2)
௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ
㣗ḧῶ㏥
46 (13.6) 3
(0.9) 33 (9.6)
1
(0.3) 49 (15.9) 3
(1.0)
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ
㛵⠇③
13 (3.8)
0
19 (5.5)
2
(0.6) 18 (5.8)
0
➽⫗③
9
(2.7)
0
10 (2.9)
0
29 (9.4)
0
⚄⤒⣔㞀ᐖ
࿡ぬ␗ᖖ
4
(1.2)
0
7
(2.0)
0
16 (5.2)
0
ᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮
2
(0.6)
0
3
(0.9)
0
28 (9.1)
1
(0.3)
㘒ឤぬ
3
(0.9)
0
3
(0.9)
0
17 (5.5)
0
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
⬺ẟ⑕
3
(0.9)
0
2
(0.6)
0
101 (32.7) 2
(0.6)
ࡑ࠺⑛⑕
25 (7.4)
0
32 (9.3)
0
5
(1.6)
1
(0.3)
Ⓨ⑈
29 (8.6)
1
(0.3) 44 (12.8) 1
(0.3) 14 (4.5)
0
࡞࠾ࠊ2 mg/kg Q3W ⩌ཬࡧ 10 mg/kg Q3W ⩌࡛ࡑࢀࡒࢀࠊ㛫㉁ᛶ⫵⑌ᝈࡣ 15 ౛㸦4.4%㸧
ཬࡧ 14 ౛㸦4.1%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ࡣ 5 ౛㸦1.5%㸧ཬࡧ 2 ౛㸦0.6%㸧ࠊ㔜ᗘࡢ⓶
⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࡣ 1 ౛㸦0.3%㸧ཬࡧ 1 ౛㸦0.3%㸧ࠊ
⚄⤒㞀ᐖ㸦ࢠ࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧ࡣ 2 ౛㸦0.6%㸧ཬࡧ 3 ౛㸦0.9%㸧ࠊ⫢ᶵ⬟㞀ᐖ
ࡣ 23 ౛㸦6.8%㸧ཬࡧ 22 ౛㸦6.4%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖࡣ 32 ౛㸦9.4%㸧ཬࡧ 35 ౛㸦10.2%㸧ࠊ
ୗᆶయᶵ⬟㞀ᐖࡣ 1 ౛㸦0.3%㸧ཬࡧ 1 ౛㸦0.3%㸧ࠊ๪⭈ᶵ⬟㞀ᐖࡣ 2 ౛㸦0.6%㸧ཬࡧ 1
౛㸦0.3%㸧ࠊ1 ᆺ⢾ᒀ⑓ࡣ 1 ౛㸦0.3%㸧ཬࡧ 2 ౛㸦0.6%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ
⭈⅖➼㸧ࡣ 4 ౛㸦1.2%㸧ཬࡧ 0 ౛ࠊ⮅⅖ࡣ 1 ౛㸦0.3%㸧ཬࡧ 0 ౛ࠊ➽⅖࣭ᶓ⣠➽⼥ゎ
⑕ࡣ 1 ౛㸦0.3%㸧ཬࡧ 0 ౛ࠊinfusion reaction ࡣ 2 ౛㸦0.6%㸧ཬࡧ 6 ౛㸦1.7%㸧࡛ㄆࡵ
ࡽࢀࡓࠋࡲࡓࠊ㔜⑕➽↓ຊ⑕ࠊ⬻⅖࣭㧊⭷⅖ࠊࡪ࡝࠺⭷⅖ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗ
ࡓࠋ
8
4㸬
㸬᪋タ࡟ࡘ࠸࡚
ᢎㄆ᮲௳࡜ࡋ࡚౑⏝ᡂ⦼ㄪᰝ㸦඲౛ㄪᰝ㸧ࡀㄢࡏࡽࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᙜヱㄪᰝࢆ㐺ษ
࡟ᐇ᪋࡛ࡁࡿ᪋タ࡛࠶ࡿᚲせࡀ࠶ࡿࠋࡑࡢୖ࡛ࠊᮏ๣ࡢᢞ୚ࡀ㐺ษ࡞ᝈ⪅ࢆデ᩿࣭≉ᐃ
ࡋࠊᮏ๣ࡢᢞ୚࡟ࡼࡾ㔜⠜࡞๪స⏝ࢆⓎ⌧ࡋࡓ㝿࡟ᑐᛂࡍࡿࡇ࡜ࡀᚲせ࡞ࡓࡵࠊ௨ୗࡢ
ձ㹼ճࡢࡍ࡭࡚ࢆ‶ࡓࡍ᪋タ࡟࠾࠸࡚౑⏝ࡍࡿ࡭ࡁ࡛࠶ࡿࠋ
ձ ᪋タ࡟ࡘ࠸࡚
ձ-1 ୗグࡢ㸦1㸧㹼㸦5㸧ࡢ࠸ࡎࢀ࠿࡟ヱᙜࡍࡿ᪋タ࡛࠶ࡿࡇ࡜ࠋ
(1) ཌ⏕ປാ኱⮧ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔➼㸦㒔㐨ᗓ┴ࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊ
ᆅᇦࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊᆅᇦࡀࢇデ⒪⑓㝔࡞࡝㸧㸦ᖹᡂ 28 ᖺ 10 ᭶ 1 ᪥᫬Ⅼ㸸
427 ᪋タ㸧
(2) ≉ᐃᶵ⬟⑓㝔㸦ᖹᡂ 28 ᖺ 9 ᭶ 1 ᪥᫬Ⅼ㸸84 ᪋タ㸧
(3) 㒔㐨ᗓ┴▱஦ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠ⑓㝔㸦ࡀࢇデ⒪㐃ᦠᣦᐃ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ
༠ຊ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ᥎㐍⑓㝔࡞࡝㸧
(4) እ᮶໬Ꮫ⒪ἲᐊࢆタ⨨ࡋࠊእ᮶໬Ꮫ⒪ἲຍ⟬ 1 ཪࡣእ᮶໬Ꮫ⒪ἲຍ⟬ 2 ࡢ᪋タᇶ‽
࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7 ᭶ 1 ᪥᫬Ⅼ㸸 2538 ᪋タ㸧
(5) ᢠᝏᛶ⭘⒆๣ฎ᪉⟶⌮ຍ⟬ࡢ᪋タᇶ‽࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7
᭶ 1 ᪥᫬Ⅼ㸸1284 ᪋タ㸧
ձ-2 ⫵⒴ࡢ໬Ꮫ⒪ἲཬࡧ๪స⏝Ⓨ⌧᫬ࡢᑐᛂ࡟༑ศ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ㸦ୗ⾲ࡢ
࠸ࡎࢀ࠿࡟ヱᙜࡍࡿ་ᖌ㸧ࡀࠊᙜヱデ⒪⛉ࡢᮏ๣࡟㛵ࡍࡿ἞⒪ࡢ㈐௵⪅࡜ࡋ࡚㓄⨨ࡉࢀ
࡚࠸ࡿࡇ࡜ࠋ
⾲
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 5 ᖺ௨ୖࡢࡀࢇ἞⒪ࡢ⮫ᗋ◊ಟࢆ⾜
ࡗ࡚࠸ࡿࡇ࡜ࠋ࠺ࡕࠊ2 ᖺ௨ୖࡣࠊࡀࢇ⸆≀⒪ἲࢆ୺࡜ࡋࡓ⮫ᗋ⭘⒆Ꮫࡢ◊ಟࢆ⾜
࡞ࡗ࡚࠸ࡿࡇ࡜ࠋ
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 4 ᖺ௨ୖࡢ⮫ᗋ⤒㦂ࢆ᭷ࡋ࡚࠸ࡿࡇ
࡜ࠋ࠺ࡕࠊ3 ᖺ௨ୖࡣࠊ⫵⒴ࡢࡀࢇ⸆≀⒪ἲࢆྵࡴ࿧྾ჾ⑓Ꮫࡢ⮫ᗋ◊ಟࢆ⾜ࡗ࡚
࠸ࡿࡇ࡜ࠋ
ղ 㝔ෆࡢ་⸆ရ᝟ሗ⟶⌮ࡢయไ࡟ࡘ࠸࡚
་⸆ရ᝟ሗ⟶⌮࡟ᚑ஦ࡍࡿᑓ௵⪅ࡀ㓄⨨ࡉࢀࠊ〇⸆௻ᴗ࠿ࡽࡢ᝟ሗ❆ཱྀࠊ᭷ຠᛶ࣭Ᏻ඲
ᛶ➼⸆Ꮫⓗ᝟ሗࡢ⟶⌮ཬࡧ་ᖌ➼࡟ᑐࡍࡿ᝟ሗᥦ౪ࠊ᭷ᐖ஦㇟ࡀⓎ⏕ࡋࡓሙྜࡢሗ࿌ᴗ
ົࠊ➼ࡀ㏿ࡸ࠿࡟⾜ࢃࢀࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
9
ճ ๪స⏝࡬ࡢᑐᛂ࡟ࡘ࠸࡚
ճ-1 ᪋タయไ࡟㛵ࡍࡿせ௳
㛫㉁ᛶ⫵⑌ᝈ➼ࡢ㔜⠜࡞๪స⏝ࡀⓎ⏕ࡋࡓ㝿࡟ࠊ24 ᫬㛫デ⒪యไࡢୗࠊᙜヱ᪋タཪࡣ
㐃ᦠ᪋タ࡟࠾࠸࡚ࠊⓎ⌧ࡋࡓ๪స⏝࡟ᛂࡌ࡚ධ㝔⟶⌮ཬࡧ CT ➼ࡢ๪స⏝ࡢ㚷ู࡟ᚲせ
࡞᳨ᰝࡢ⤖ᯝࡀᙜ᪥୰࡟ᚓࡽࢀࠊ┤ࡕ࡟ᑐᛂྍ⬟࡞యไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
㻌
䐡-2 ་⒪ᚑ஦⪅࡟ࡼࡿ᭷ᐖ஦㇟ᑐᛂ࡟㛵ࡍࡿせ௳
ࡀࢇデ⒪࡟ᦠࢃࡿᑓ㛛ⓗ࡞▱㆑ཬࡧᢏ⬟ࢆ᭷ࡍࡿ་⒪ᚑ஦⪅ࡀ๪స⏝ࣔࢽࢱࣜࣥࢢࢆ
ྵࡵࡓⱞ③ࡢࢫࢡ࣮ࣜࢽࣥࢢࢆ⾜࠸୺἞་࡜᝟ሗࢆඹ᭷࡛ࡁࡿࢳ࣮࣒་⒪యไࡀᩚഛ
ࡉࢀ࡚࠸ࡿࡇ࡜ࠋ࡞࠾ࠊᩚഛయไ࡟ࡘ࠸࡚ࠊࡀࢇᝈ⪅࡜ࡑࡢᐙ᪘࡟༑ศ࡟࿘▱ࡉࢀ࡚࠸
ࡿࡇ࡜ࠋ
㻌
䐡-3 ๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚
๪స⏝㸦㛫㉁ᛶ⫵⑌ᝈ࡟ຍ࠼ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ࠊ⫢ᶵ⬟㞀ᐖࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶
㛫㉁ᛶ⭈⅖➼㸧ࠊෆศἪ㞀ᐖ㸦ୗᆶయᶵ⬟㞀ᐖࠊ⏥≧⭢ᶵ⬟㞀ᐖࠊ๪⭈ᶵ⬟㞀ᐖ㸧ࠊ1 ᆺ
⢾ᒀ⑓ࠊࡪ࡝࠺⭷⅖ࠊ➽⅖࣭ᶓ⣠➽⼥ゎ⑕ࠊ⮅⅖ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊ
ከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧
ࠊinfusion reactionࠊ⬻⅖࣭㧊⭷⅖ࠊ㔜⑕➽↓ຊ⑕ࠊ⚄⤒㞀ᐖ㸦ࢠ
࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧ࠊᚰ➽⅖➼㸧࡟ᑐࡋ࡚ࠊᙜヱ᪋タཪࡣ㏆㞄་⒪ᶵ㛵ࡢᑓ㛛ᛶࢆ
᭷ࡍࡿ་ᖌ࡜㐃ᦠࡋ㸦๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚ᣦᑟཬࡧᨭ᥼ࢆཷࡅࡽࢀࡿ᮲௳࡟࠶
ࡿࡇ࡜㸧ࠊ┤ࡕ࡟㐺ษ࡞ฎ⨨ࡀ࡛ࡁࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
10
5㸬
㸬ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
࠙Ᏻ඲ᛶࠚ
ձ ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣᮏ๣ࡢᢞ୚ࡀ⚗ᚷ࡜ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᢞ୚ࢆ⾜
ࢃ࡞࠸ࡇ࡜ࠋ
y
ᮏ๣ࡢᡂศ࡟ᑐࡋ㐣ᩄ⑕ࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
y
ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿᝈ⪅
ղ ἞⒪๓ࡢホ౯࡟࠾࠸࡚ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢᢞ୚ࡣ᥎ዡࡉࢀ࡞࠸
ࡀࠊ௚ࡢ἞⒪㑅ᢥ⫥ࡀ࡞࠸ሙྜ࡟㝈ࡾࠊៅ㔜࡟ᮏ๣ࢆ౑⏝ࡍࡿࡇ࡜ࢆ⪃៖࡛ࡁࡿࠋ
y
㛫㉁ᛶ⫵⑌ᝈࡢྜేཪࡣ᪤ ࡢ࠶ࡿᝈ⪅
y
⬚㒊⏬ീ᳨ᰝ࡛㛫㉁ᙳࢆㄆࡵࡿᝈ⪅ཬࡧάືᛶࡢᨺᑕ⥺⫵⮚⅖ࡸឤᰁᛶ⫵⅖
➼ࡢ⫵࡟⅖⑕ᛶኚ໬ࡀࡳࡽࢀࡿᝈ⪅
y
⮬ᕫච␿⑌ᝈࡢྜేࠊཪࡣ៏ᛶⓗ࡞ⱝࡋࡃࡣ෌Ⓨᛶࡢ⮬ᕫච␿⑌ᝈࡢ᪤ Ṕࡢ
࠶ࡿᝈ⪅
y
ECOG Performance Status 3-4
䠄ὀ1䠅
䛾ᝈ⪅
࠙᭷ຠᛶࠚ
ձ ୗグࡢᝈ⪅࡟࠾࠸࡚ᮏ๣ࡢ᭷ຠᛶࡀ᳨ドࡉࢀ࡚࠸ࡿࠋ
y
໬Ꮫ⒪ἲṔࡢ࡞࠸ࠊEGFR 㑇ఏᏊኚ␗㝜ᛶࠊALK ⼥ྜ㑇ఏᏊ㝜ᛶཬࡧ PD-L1
㝧ᛶ㸦TPSӍ50%㸧ࡢษ㝖୙⬟࡞㐍⾜࣭෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴ᝈ⪅
y
ࣉࣛࢳࢼ〇๣ࢆྵࡴ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿ PD-L1 㝧ᛶ㸦TPSӍ1%㸧ࡢษ㝖୙⬟࡞
㐍⾜࣭෌Ⓨࡢ㠀ᑠ⣽⬊⫵⒴ᝈ⪅㸦࡞࠾ࠊEGFR 㑇ఏᏊኚ␗㝧ᛶཪࡣ ALK ⼥ྜ
㑇ఏᏊ㝧ᛶࡢᝈ⪅࡛ࡣࠊࡑࢀࡒࢀ EGFR ࢳࣟࢩࣥ࢟ࢼ࣮ࢮ㜼ᐖ๣ཪࡣ ALK ࢳ
ࣟࢩࣥ࢟ࢼ࣮ࢮ㜼ᐖ๣ࡢ἞⒪Ṕࢆ᭷ࡍࡿᝈ⪅㸧
࡞࠾ࠊTPSࡣ࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧ࡢࢥࣥࣃࢽ࢜ࣥデ᩿⸆㸦㈍኎ྡ㸸
PD-L1 IHC 22C3 pharmDx ࠕࢲࢥࠖ㸧ࢆ⏝࠸࡚ ᐃࡍࡿࡇ࡜ࠋ
ղ ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ᑐࡍࡿᮏ๣ࡢᢞ୚ཬࡧ౑⏝᪉ἲ࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢ᭷ຠᛶࡀ
☜❧ࡉࢀ࡚࠾ࡽࡎࠊᮏ๣ࡢᢞ୚ᑐ㇟࡜࡞ࡽ࡞࠸ࠋ
y
⾡ᚋ⿵ຓ໬Ꮫ⒪ἲࠋ
y
௚ࡢᢠᝏᛶ⭘⒆๣࡜ࡢే⏝ࠋ
㸦ὀ1㸧
Score
0
1
2
3
4
ECOG ࡢ Performance Status㸦PS㸧
ᐃ⩏
඲ࡃၥ㢟࡞ࡃάື࡛ࡁࡿࠋⓎ⑓๓࡜ྠࡌ᪥ᖖ⏕άࡀไ㝈࡞ࡃ⾜࠼ࡿࠋ
⫗యⓗ࡟⃭ࡋ࠸άືࡣไ㝈ࡉࢀࡿࡀࠊṌ⾜ྍ⬟࡛ࠊ㍍సᴗࡸᗙࡗ࡚ࡢసᴗࡣ⾜࠺ࡇ࡜ࡀ࡛ࡁࡿࠋ
౛㸸㍍࠸ᐙ஦ࠊ஦ົసᴗ
Ṍ⾜ྍ⬟࡛⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣࡍ࡭࡚ྍ⬟ࡔࡀసᴗࡣ࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࡣ࣋ࢵࢻእ࡛㐣ࡈࡍࠋ
㝈ࡽࢀࡓ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡋ࠿࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࢆ࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
඲ࡃືࡅ࡞࠸ࠋ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣ඲ࡃ࡛ࡁ࡞࠸ࠋ᏶඲࡟࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
11
ճ ⫵⒴デ⒪࢞࢖ࢻࣛ࢖ࣥ㸦᪥ᮏ⫵⒴Ꮫ఍⦅㸧࡟࠾࠸࡚ࠊECOG Performance Status 0㹼1
㸦ὀ 1㸧
࡛ 75 ṓ௨ୖࠊཪࡣ ECOG Performance Status 2㸦ὀ 1㸧ࡢᝈ⪅࡛ࡣࠊ➨ 3 ୡ௦ᢠ⒴
๣㸦ࢻࢭࢱ࢟ࢭࣝ➼㸧ࡢ༢๣ᢞ୚ࡀ᥎ዡࡉࢀ࡚࠾ࡾࠊࣉࣛࢳࢼ〇๣ࡢ౑⏝᥎ዡᗘࡣ
ప࠸ࡓࡵ౑⏝ࡉࢀ࡞࠸ࢣ࣮ࢫࡀ࠶ࡿࠋ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿᝈ⪅࡟౑⏝ࡍࡿሙྜࠊࣉ
ࣛࢳࢼ〇๣ࡢ๓἞⒪ࡀ࡞ࡃ࡜ࡶ➨ 3 ୡ௦ᢠ⒴๣༢๣࡛ࡢ἞⒪Ṕࢆ᭷ࡍࡿᝈ⪅࡟࠾࠸
࡚ࡣࠊᮏ๣ࡢᢞ୚ࢆ⪃៖࡛ࡁࡿࠋ
12
6㸬
㸬ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
ձ ῧ௜ᩥ᭩➼࡟ຍ࠼ࠊ〇㐀㈍኎ᴗ⪅ࡀᥦ౪ࡍࡿ㈨ᩱ➼࡟ᇶ࡙ࡁᮏ๣ࡢ≉ᛶཬࡧ㐺ṇ౑
⏝ࡢࡓࡵ࡟ᚲせ࡞᝟ሗࢆ༑ศ࡟⌮ゎࡋ࡚࠿ࡽ౑⏝ࡍࡿࡇ࡜ࠋ
ղ ἞⒪㛤ጞ࡟ඛ❧ࡕࠊᝈ⪅ཪࡣࡑࡢᐙ᪘࡟᭷ຠᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋࠊྠពࢆᚓ
࡚࠿ࡽᢞ୚ࡍࡿࡇ࡜ࠋ
ճ ୺࡞๪స⏝ࡢ࣐ࢿࢪ࣓ࣥࢺ࡟ࡘ࠸࡚
y
㛫㉁ᛶ⫵⑌ᝈࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚࡟࠶ࡓࡗ࡚ࡣࠊึᮇ⑕
≧㸦ᜥษࢀࠊ࿧྾ᅔ㞴ࠊတႿ➼㸧ࡢ☜ㄆཬࡧ⬚㒊 X ⥺᳨ᰝࡢᐇ᪋➼ࠊほᐹࢆ༑
ศ࡟⾜࠺ࡇ࡜ࠋࡲࡓࠊᚲせ࡟ᛂࡌ࡚⬚㒊 CTࠊ⾑Ύ࣐࣮࣮࢝➼ࡢ᳨ᰝࢆᐇ᪋ࡍ
ࡿࡇ࡜ࠋ
y
infusion reaction ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࠋinfusion reaction ࡀㄆࡵࡽࢀࡓሙྜ࡟
ࡣࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺࡜࡜ࡶ࡟ࠊ⑕≧ࡀᅇ᚟ࡍࡿࡲ࡛ᝈ⪅ࡢ≧ែࢆ༑ศ࡟ほᐹ
ࡍࡿࡇ࡜ࠋ
y
⏥≧⭢ᶵ⬟㞀ᐖࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚㛤ጞ๓ཬࡧᢞ୚ᮇ㛫
୰ࡣᐃᮇⓗ࡟⏥≧⭢ᶵ⬟᳨ᰝ㸦TSHࠊ㐟㞳 T3ࠊ㐟㞳 T4 ➼ࡢ ᐃ㸧ࢆᐇ᪋ࡍࡿ
ࡇ࡜ࠋ
y
⫢ᶵ⬟㞀ᐖࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚㛤ጞ๓ཬࡧᢞ୚ᮇ㛫୰ࡣ
ᐃᮇⓗ࡟⫢ᶵ⬟᳨ᰝ㸦ASTࠊALTࠊγ-GTPࠊAl-Pࠊࣅࣜࣝࣅࣥ➼ࡢ ᐃ㸧ࢆᐇ᪋
ࡍࡿࡇ࡜ࠋ
y
ࡪ࡝࠺⭷⅖㸦⹿ᙬ⅖ཬࡧ⹿ᙬẟᵝయ⅖ࢆྵࡴ㸧➼ࡢ㔜⠜࡞║㞀ᐖࡀ࠶ࡽࢃࢀࡿ
ࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᐃᮇⓗ࡟║ࡢ␗ᖖࡢ᭷↓ࢆ☜ㄆࡍࡿࡇ࡜ࠋࡲࡓࠊ║ࡢ␗ᖖࡀ
ㄆࡵࡽࢀࡓሙྜ࡟ࡣࠊ㏿ࡸ࠿࡟་⒪ᶵ㛵ࢆཷデࡍࡿࡼ࠺ᝈ⪅ࢆᣦᑟࡍࡿࡇ࡜ࠋ
y
ᮏ๣ࡢᢞ୚࡟ࡼࡾࠊ㐣ᗘࡢච␿཯ᛂ࡟㉳ᅉࡍࡿ࡜⪃࠼ࡽࢀࡿᵝࠎ࡞⑌ᝈࡸ⑓ែ
ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࠋ␗ᖖࡀㄆࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓ
ᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿
཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊᮏ๣ࡢఇ⸆ཪࡣ୰Ṇࠊཬࡧ๪⭈⓶㉁࣍
ࣝࣔࣥ๣ࡢᢞ୚➼ࢆ⪃៖ࡍࡿࡇ࡜ࠋ࡞࠾ࠊ๪⭈⓶㉁࣍ࣝࣔࣥࡢᢞ୚࡟ࡼࡾ๪స
⏝ࡢᨵၿࡀㄆࡵࡽࢀ࡞࠸ሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝࣔࣥ௨እࡢච␿ᢚไ๣ࡢ㏣ຍ
ࡶ⪃៖ࡍࡿࡇ࡜ࠋ
y
ᢞ୚⤊஢ᚋࠊᩘ㐌㛫࠿ࡽᩘ࢝᭶⤒㐣ࡋ࡚࠿ࡽ๪స⏝ࡀⓎ⌧ࡍࡿࡇ࡜ࡀ࠶ࡿࡓࡵࠊ
ᮏ๣ࡢᢞ୚⤊஢ᚋ࡟ࡶ๪స⏝ࡢⓎ⌧࡟༑ศ࡟ὀពࡍࡿࡇ࡜ࠋ
y
1 ᆺ⢾ᒀ⑓㸦๻⑕ 1 ᆺ⢾ᒀ⑓ࢆྵࡴ㸧ࡀ࠶ࡽࢃࢀࠊ⢾ᒀ⑓ᛶࢣࢺ࢔ࢩࢻ࣮ࢩࢫ
࡟⮳ࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊཱྀῬࠊᝏᚰࠊ჎ྤ➼ࡢ⑕≧ࡢⓎ⌧ࡸ⾑⢾್ࡢୖ᪼࡟༑
ศὀពࡍࡿࡇ࡜ࠋ1 ᆺ⢾ᒀ⑓ࡀ␲ࢃࢀࡓሙྜ࡟ࡣᢞ୚ࢆ୰Ṇࡋࠊ࢖ࣥࢫࣜࣥ〇
๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇ࡜ࠋ
մ ᮏ๣ࡢ⮫ᗋヨ㦂࡟࠾࠸࡚ࠊᢞ୚㛤ጞ࠿ࡽ 9 㐌┠ࠊࡑࢀ௨㝆ࡣࠊᢞ୚㛤ጞ࠿ࡽ 1 ᖺ㛫
ࡣ 3 ᅇᢞ୚⤊஢ࡈ࡜࡟᭷ຠᛶࡢホ౯ࢆ⾜ࡗ࡚࠸ࡓࡇ࡜ࢆཧ⪃࡟ࠊᮏ๣ᢞ୚୰ࡣᐃᮇ
ⓗ࡟⏬ീ᳨ᰝ࡛ຠᯝࡢ☜ㄆࢆ⾜࠺ࡇ࡜ࠋ
13
ูῧ㸲
᭱㐺౑⏝᥎㐍࢞࢖ࢻࣛ࢖ࣥ
࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧
㸦㈍኎ྡ㸸࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 20 mgࠊ࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 100 mg㸧
㹼ᝏᛶ㯮Ⰽ⭘㹼
ᖹᡂ㸰㸷ᖺ㸰᭶
ཌ⏕ປാ┬
┠ḟ
1.
2.
3.
4.
5.
6.
ࡣࡌࡵ࡟
ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
⮫ᗋᡂ⦼
᪋タ࡟ࡘ࠸࡚
ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
P2
P3
P4
P10
P12
P13
1
1㸬
㸬ࡣࡌࡵ࡟
་⸆ရࡢ᭷ຠᛶ࣭Ᏻ඲ᛶࡢ☜ಖࡢࡓࡵ࡟ࡣࠊῧ௜ᩥ᭩➼࡟ᇶ࡙࠸ࡓ㐺ṇ࡞౑⏝ࡀồࡵ
ࡽࢀࡿࠋࡉࡽ࡟ࠊ㏆ᖺࡢ⛉Ꮫᢏ⾡ࡢ㐍Ṍ࡟ࡼࡾࠊᢠయ་⸆ရ࡞࡝ࡢ㠉᪂ⓗ࡞᪂つస⏝ᶵ
ᗎ་⸆ရࡀᢎㄆࡉࢀࡿ୰࡛ࠊࡇࢀࡽࡢ་⸆ရࢆ┿࡟ᚲせ࡞ᝈ⪅࡟ᥦ౪ࡍࡿࡇ࡜ࡀႚ⥭ࡢ
ㄢ㢟࡜࡞ࡗ࡚࠾ࡾࠊ
⤒῭㈈ᨻ㐠Ⴀ࡜ᨵ㠉ࡢᇶᮏ᪉㔪 2016
㸦ᖹᡂ 28 ᖺ㸴᭶㸰᪥㛶㆟Ỵᐃ㸧
࡟࠾࠸࡚ࡶࠊ㠉᪂ⓗ་⸆ရ➼ࡢ౑⏝ࡢ᭱㐺໬᥎㐍ࢆᅗࡿࡇ࡜࡜ࡉࢀ࡚࠸ࡿࠋ
᪂つస⏝ᶵᗎ་⸆ရࡣࠊ⸆⌮స⏝ࡸᏳ඲ᛶࣉࣟࣇ࢓࢖ࣝࡀ᪤Ꮡࡢ་⸆ရ࡜᫂ࡽ࠿࡟␗
࡞ࡿࡇ࡜ࡀ࠶ࡿࠋࡇࡢࡓࡵࠊ᭷ຠᛶཬࡧᏳ඲ᛶ࡟㛵ࡍࡿ᝟ሗࡀ༑ศ⵳✚ࡍࡿࡲ࡛ࡢ㛫ࠊ
ᙜヱ་⸆ရࡢᜠᜨࢆᙉࡃཷࡅࡿࡇ࡜ࡀᮇᚅࡉࢀࡿᝈ⪅࡟ᑐࡋ࡚౑⏝ࡍࡿ࡜࡜ࡶ࡟ࠊ๪స
⏝ࡀⓎ⌧ࡋࡓ㝿࡟ᚲせ࡞ᑐᛂࢆ࡜ࡿࡇ࡜ࡀྍ⬟࡞୍ᐃࡢせ௳ࢆ‶ࡓࡍ་⒪ᶵ㛵࡛౑⏝
ࡍࡿࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ
ࡋࡓࡀࡗ࡚ࠊᮏ࢞࢖ࢻࣛ࢖࡛ࣥࡣࠊ㛤Ⓨẁ㝵ࡸࡇࢀࡲ࡛࡟ᚓࡽࢀ࡚࠸ࡿ་Ꮫ⸆Ꮫⓗ࣭
⛉Ꮫⓗぢᆅ࡟ᇶ࡙ࡁࠊ௨ୗࡢ་⸆ရࡢ᭱㐺࡞౑⏝ࢆ᥎㐍ࡍࡿほⅬ࠿ࡽᚲせ࡞せ௳ࠊ⪃࠼
᪉ཬࡧ␃ព஦㡯ࢆ♧ࡍࠋ
࡞࠾ࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ⊂❧⾜ᨻἲே་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓࠊබ┈♫ᅋἲே᪥ᮏ
⮫ᗋ⭘⒆Ꮫ఍ࠊ୍⯡♫ᅋἲே᪥ᮏ⮫ᗋෆ⛉་఍ཬࡧබ┈♫ᅋἲே᪥ᮏ⓶⭵⛉Ꮫ఍ࡢ༠ຊ
ࡢࡶ࡜సᡂࡋࡓࠋ
ᑐ㇟࡜࡞ࡿ་⸆ရ㸸࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 20 mgࠊ࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 100 mg㸦୍
⯡ྡ㸸࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧
㸧
ᑐ㇟࡜࡞ࡿຠ⬟ཪࡣຠᯝ㸸᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘
ᑐ㇟࡜࡞ࡿ⏝ἲཬࡧ⏝㔞㸸㏻ᖖࠊᡂே࡟ࡣࠊ࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮࠼㸧࡜ࡋ࡚ࠊ1
ᅇ 2mg/kg㸦య㔜㸧ࢆ 3 㐌㛫㛫㝸࡛ 30 ศ㛫࠿ࡅ࡚Ⅼ⁲㟼ὀࡍࡿࠋ
〇㐀㈍ ኎ ᴗ ⪅㸸MSD ᰴᘧ఍♫
2
2㸬
㸬ᮏ๣ࡢ≉ᚩࠊస⏝ᶵᗎ
࢟࢖ࢺ࣮ࣝࢲⅬ⁲㟼ὀ 20 mg ཬࡧ 100 mg㸦୍⯡ྡ㸸࣒࣌ࣈࣟࣜࢬ࣐ࣈ㸦㑇ఏᏊ⤌᥮
࠼㸧
ࠊ௨ୗࠕᮏ๣ࠖ࡜࠸࠺ࠋ㸧ࡣࠊPD-1㸦programmed cell death-1㸧࡜ࡑࡢࣜ࢞ࣥࢻ࡛࠶
ࡿ PD-L1 ཬࡧ PD-L2 ࡜ࡢ⤖ྜࢆ┤᥋㜼ᐖࡍࡿࠊ
ࣄࢺ໬ IgG4 ࣔࣀࢡ࣮ࣟࢼࣝᢠయ࡛࠶ࡿࠋ
PD-1 ⤒㊰ࡣ T ⣽⬊ච␿┘どᶵᵓ࠿ࡽ㏨ࢀࡿࡓࡵ࡟ࡀࢇ⣽⬊ࡀ฼⏝ࡍࡿ୺࡞ච␿ไᚚ
ࢫ࢖ࢵࢳ࡛ࠊPD-1 ࡣࠊ೺ᗣ࡞≧ែ࡟࠾࠸࡚άᛶᆺ T ⣽⬊ࡢ⣽⬊⾲㠃࡟Ⓨ⌧ࡋࠊ⮬ᕫච
␿཯ᛂࢆྵࡴ୙ᚲせཪࡣ㐣๫࡞ච␿཯ᛂࢆไᚚࡍࡿࠋࡍ࡞ࢃࡕࠊPD-1 ࡣࣜ࢞ࣥࢻ࡜⤖
ྜࡍࡿࡇ࡜࡟ࡼࡾᢠཎཷᐜయ࡟ࡼࡿࢩࢢࢼࣝఏ㐩ࢆ㈇࡟ไᚚࡍࡿཷᐜయ࡛࠶ࡿࠋPD-L1
ࡢṇᖖ⤌⧊࡟࠾ࡅࡿⓎ⌧ࡣࢃࡎ࠿࡛࠶ࡿࡀࠊከࡃࡢࡀࢇ⣽⬊࡛ࡣ T ⣽⬊ࡢാࡁࢆᢚ࠼ࡿ
࡯࡝㐣๫࡟Ⓨ⌧ࡋ࡚࠸ࡿࠋࡀࢇ⣽⬊࡟࠾ࡅࡿ PD-L1 ࡢ㧗Ⓨ⌧ࡣࠊ⭈⣽⬊⒴ࠊ⮅⮚⒴ࠊ
⫢⣽⬊⒴ࠊ༸ᕢ⒴ࠊ㠀ᑠ⣽⬊⫵⒴➼ࡢᵝࠎ࡞ࡀࢇ࡛ணᚋ୙ⰋᅉᏊ࡛࠶ࡾࠊప࠸⏕Ꮡ⋡࡜
ࡢ┦㛵ᛶࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ
」ᩘࡢࡀࢇࡢ⮫ᗋⓗணᚋ࡜ PD-L1 Ⓨ⌧ࡢ┦㛵ᛶ࠿ࡽࠊPD-1 ࡜ PD-L1 ࡢ⤒㊰ࡣ⭘⒆ࡢ
ච␿ᅇ㑊࡟࠾࠸࡚㔜せ࡞ᙺ๭ࢆᢸ࠺ࡇ࡜ࡀ♧၀ࡉࢀ࡚࠾ࡾࠊ᪂ࡓ࡞ࡀࢇ἞⒪ࡢᶆⓗ࡜ࡋ
࡚ᮇᚅࡉࢀ࡚࠸ࡿࠋ
ᮏ๣ࡣࠊPD-1 ࡜ PD-L1 ཬࡧ PD-L2 ࡢ୧ࣜ࢞ࣥࢻࡢ⤖ྜࢆ㜼ᐖࡍࡿࡇ࡜࡟ࡼࡾࠊ⭘⒆
ᚤᑠ⎔ቃ୰ࡢ⭘⒆≉␗ⓗ⣽⬊യᐖᛶ T ࣜࣥࣃ⌫ࢆάᛶ໬ࡉࡏࠊᢠ⭘⒆ච␿ࢆ෌άᛶ໬ࡍ
ࡿࡇ࡜࡛ᢠ⭘⒆ຠᯝࢆⓎ᥹ࡍࡿࠋ
ᮏ๣ࡢస⏝ᶵᗎ࡟ᇶ࡙ࡃ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝➼ࡀ࠶ࡽࢃࢀࠊ㔜⠜ཪࡣṚஸ࡟
⮳ࡿྍ⬟ᛶࡀ࠶ࡿࠋᮏ๣ࡢᢞ୚୰ཬࡧᢞ୚ᚋ࡟ࡣࠊᝈ⪅ࡢほᐹࢆ༑ศ࡟⾜࠸ࠊ␗ᖖࡀㄆ
ࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺
ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝ
ࣔࣥ๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ᚲせࡀ࠶ࡿࠋ
3
3㸬
㸬⮫ᗋᡂ⦼
᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘ࡢᢎㄆ᫬࡟ホ౯ࢆ⾜ࡗࡓ୺࡞⮫ᗋヨ㦂ࡢᡂ⦼ࢆ♧ࡍࠋ
࠙᭷ຠᛶࠚ
ձᅜෆ➨Ϩb ┦ヨ㦂㸦KEYNOTE-041 ヨ㦂㸧
໬Ꮫ⒪ἲṔࡢ࡞࠸ཪࡣ࢖ࣆ࣒࣐ࣜࣈ㸦㑇ఏᏊ⤌᥮࠼㸧㸦௨ୗࠕ࢖ࣆ࣒࣐ࣜࣈࠖ࡜࠸࠺ࠋ㸧
ࢆྵࡲ࡞࠸ 2 ࣞࢪ࣓ࣥࡲ࡛ࡢ໬Ꮫ⒪ἲṔࢆ᭷ࡍࡿ᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘ᝈ⪅ 42 ౛
㸦᭷ຠᛶゎᯒᑐ㇟ 37 ౛㸧ࢆᑐ㇟࡟ࠊᮏ๣ 2 mg/kg 3 㐌㛫㛫㝸㸦௨ୗࠕQ3Wࠖ࡜࠸࠺ࠋ
㸧
ᢞ୚ࡢ᭷ຠᛶཬࡧᏳ඲ᛶࡀ᳨ウࡉࢀࡓࠋ࡞࠾ࠊ⏬ീホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡓሙྜ࡟ࠊ
⑌ᝈ㐍⾜ࢆ♧ࡍ⑕≧ࡀㄆࡵࡽࢀ࡞࠸➼ࡢ⮫ᗋⓗ࡟Ᏻᐃࡋ࡚࠸ࡿᝈ⪅࡛ࡣࠊḟᅇ௨㝆ࡢ⏬
ീホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡿࡲ࡛ᮏ๣ࡢᢞ୚ࢆ⥅⥆ࡍࡿࡇ࡜ࡀྍ⬟࡜ࡉࢀࡓࠋ୺せホ
౯㡯┠࡛࠶ࡿዌຠ⋡
㹙RECIST ࢞࢖ࢻࣛ࢖ࣥ 1.1 ∧࡟ᇶ࡙ࡃ୰ኸุᐃ࡟ࡼࡿ᏶඲ዌຠ
㸦CR㸧
ཪࡣ㒊ศዌຠ㸦PR㸧
㹛ࡣࠊ24%㸦95%ಙ㢗༊㛫㸸12㹼41㸧࡛࠶ࡗࡓࠋ
ղᾏእ➨ϩ┦ヨ㦂㸦KEYNOTE-002 ヨ㦂㸧
࢖ࣆ࣒࣐ࣜࣈ࡟ࡼࡿ἞⒪Ṕࢆ᭷ࡍࡿ᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘ᝈ⪅ࢆᑐ㇟࡟ࠊᮏ๣ 2
mg/kg Q3W ᢞ୚ཬࡧ 10 mg/kg Q3W ᢞ୚ࡢ᭷ຠᛶཬࡧᏳ඲ᛶࡀࠊ໬Ꮫ⒪ἲ㸦ࢲ࢝ࣝࣂࢪ
ࣥࠊࢸࣔࢰ࣑ࣟࢻࠊ࢝ࣝ࣎ࣉࣛࢳࣥࠊࣃࢡࣜࢱ࢟ࢭࣝཪࡣ࢝ࣝ࣎ࣉࣛࢳࣥ㸩ࣃࢡࣜࢱ࢟
ࢭࣝࠊ௨ୗࠕICC ⩌ࠖ࡜࠸࠺ࠋ㸧ࢆᑐ↷࡜ࡋ᳨࡚ウࡉࢀࡓࠋ࡞࠾ࠊ⏬ീホ౯࡛⑌ᝈ㐍⾜
ࡀㄆࡵࡽࢀࡓሙྜ࡟ࠊ⑌ᝈ㐍⾜ࢆ♧ࡍ⑕≧ࡀㄆࡵࡽࢀ࡞࠸➼ࡢ⮫ᗋⓗ࡟Ᏻᐃࡋ࡚࠸ࡿᝈ
⪅࡛ࡣࠊḟᅇ௨㝆ࡢ⏬ീホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡿࡲ࡛ᮏ⸆ࡢᢞ୚ࢆ⥅⥆ࡍࡿࡇ࡜ࡀ
ྍ⬟࡜ࡉࢀࡓࠋ୺せホ౯㡯┠ࡣ඲⏕Ꮡᮇ㛫㸦OS㸧ཬࡧ↓ቑᝏ⏕Ꮡᮇ㛫㸦PFS㸧࡜ࡉࢀࠊ
ᮏ๣ࡣ໬Ꮫ⒪ἲ࡜ẚ㍑ࡋ࡚ࠊPFS ࢆ᭷ព࡟ᘏ㛗ࡋࡓࠋ
OS ࡢ Kaplan-Meier ᭤⥺
4
PFS ࡢ Kaplan-Meier ᭤⥺
ճᾏእ➨Ϫ┦ヨ㦂㸦KEYNOTE-006 ヨ㦂㸧
࢖ࣆ࣒࣐ࣜࣈ࡟ࡼࡿ἞⒪Ṕࡢ࡞࠸ཪࡣ࢖ࣆ࣒࣐ࣜࣈࢆྵࡲ࡞࠸ 1 ࣞࢪ࣓ࣥࡲ࡛ࡢ໬Ꮫ
⒪ἲṔࢆ᭷ࡍࡿ᰿἞ษ㝖୙⬟࡞ᝏᛶ㯮Ⰽ⭘ᝈ⪅ࢆᑐ㇟࡟ࠊᮏ๣ 10 mg/kg Q3W ᢞ୚ཬࡧ
10 mg/kg 2 㐌㛫㛫㝸㸦௨ୗࠕQ2Wࠖ࡜࠸࠺ࠋ㸧ᢞ୚ࡢ᭷ຠᛶཬࡧᏳ඲ᛶࡀࠊ࢖ࣆ࣒࣐ࣜ
ࣈࢆᑐ↷࡜ࡋ᳨࡚ウࡉࢀࡓࠋ࡞࠾ࠊ⏬ീホ౯࡛⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡓሙྜ࡟ࠊ⑌ᝈ㐍⾜
ࢆ♧ࡍ⑕≧ࡀㄆࡵࡽࢀ࡞࠸➼ࡢ⮫ᗋⓗ࡟Ᏻᐃࡋ࡚࠸ࡿᝈ⪅࡛ࡣࠊḟᅇ௨㝆ࡢ⏬ീホ౯࡛
⑌ᝈ㐍⾜ࡀㄆࡵࡽࢀࡿࡲ࡛ᮏ๣ࡢᢞ୚ࢆ⥅⥆ࡍࡿࡇ࡜ࡀྍ⬟࡜ࡉࢀࡓࠋ୺せホ౯㡯┠ࡣ
඲⏕Ꮡᮇ㛫㸦௨ୗࠕOSࠖ࡜࠸࠺ࠋ
㸧ཬࡧ↓ቑᝏ⏕Ꮡᮇ㛫㸦௨ୗࠕPFSࠖ࡜࠸࠺ࠋ㸧࡜ࡉࢀࠊ
ᮏ๣ࡣ࢖ࣆ࣒࣐ࣜࣈ࡜ẚ㍑ࡋ࡚ࠊOS ཬࡧ PFS ࢆ᭷ព࡟ᘏ㛗ࡋࡓ
5
OS ࡢ Kaplan-Meier ᭤⥺
PFS ࡢ Kaplan-Meier ᭤⥺
6
࠙Ᏻ඲ᛶࠚ
䐟ᅜෆ➨Ϩb ┦ヨ㦂㸦KEYNOTE-041 ヨ㦂㸧
᭷ᐖ஦㇟ࡣࠊ41/42 ౛㸦97.6%㸧࡟ㄆࡵࡽࢀࠊ἞㦂⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ
஦㇟ࡣࠊ34/42 ౛㸦81.0%㸧࡟ㄆࡵࡽࢀࡓࠋⓎ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ࡜࠾ࡾ࡛
࠶ࡗࡓࠋ
⾲ Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝㸦Ᏻ඲ᛶゎᯒᑐ㇟㞟ᅋ㸧
౛ᩘ㸦%㸧
SOC
PT
㸦MedDRA ver.18.0㸧
2 mg/kg Q3W⩌
42౛
඲Grades
඲๪స⏝
Grades 3 ௨ୖ
34
(81.0)
8
(19.0)
4
(9.5)
0
(0.0)
3
(7.1)
0
(0.0)
5
(11.9)
0
(0.0)
3
3
(7.1)
(7.1)
0
0
(0.0)
(0.0)
6
6
3
(14.3)
(14.3)
(7.1)
0
0
0
(0.0)
(0.0)
(0.0)
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟పୗ⑕
⫶⭠㞀ᐖ
ୗ⑩
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
೏ᛰឤ
⮫ᗋ᳨ᰝ
࢔ࢫࣃࣛࢠࣥ㓟࢔࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮቑຍ
ዲ㓟⌫ᩘቑຍ
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
ࡑ࠺⑛⑕
ᩬ≧ୣ⑈≧⓶⑈
ᑜᖖᛶⓑᩬ
࡞࠾ࠊ㛫㉁ᛶ⫵⑌ᝈ 1 ౛㸦2.4%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 2 ౛㸦4.8%㸧ࠊ⫢ᶵ⬟㞀ᐖ 3
౛㸦7.1%㸧ࠊୗᆶయᶵ⬟㞀ᐖ 2 ౛㸦4.8%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ 6 ౛㸦14.3%㸧ࠊinfusion reaction
1 ౛㸦2.4%㸧ཬࡧࡪ࡝࠺⭷⅖ 1 ౛㸦2.4%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ⚄⤒㞀ᐖ㸦ࢠ࣭ࣛࣥࣂ
࣮ࣞ⑕ೃ⩌➼㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧ࠊ๪⭈㞀ᐖࠊ1 ᆺ⢾ᒀ⑓ࠊ㔜ᗘࡢ
⓶⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࠊ⮅⅖ࠊ➽⅖࣭ᶓ⣠➽⼥ゎ⑕ࠊ
㔜⑕➽↓ຊ⑕ࠊ⬻⅖࣭㧊⭷⅖ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
䐠ᾏእ➨ϩ┦ヨ㦂㸦KEYNOTE-002 ヨ㦂㸧
᭷ᐖ஦㇟ࡣࠊ
2 mg/kg Q3W ⩌ 172/178 ౛
㸦96.6%㸧
ࠊ
10 mg/kg Q3W ⩌ 178/179 ౛
㸦99.4%㸧
ཬࡧ ICC ⩌ 167/171 ౛㸦97.7%㸧࡟ㄆࡵࡽࢀࠊ἞㦂⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ
஦㇟ࡣࠊࡑࢀࡒࢀ 121/178 ౛㸦68.0%㸧ࠊ133/179 ౛㸦74.3%㸧ཬࡧ 138/171 ౛㸦80.7%㸧
࡟ㄆࡵࡽࢀࡓࠋ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ࡜࠾ࡾ࡛࠶ࡗࡓࠋ
7
⾲ ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝㸦Ᏻ඲ᛶゎᯒᑐ㇟㞟ᅋ㸧
SOC
PT
㸦MedDRA ver.18.0㸧
඲๪స⏝
⾑ᾮ࠾ࡼࡧࣜࣥࣃ⣔㞀ᐖ
㈋⾑
ⓑ⾑⌫ῶᑡ⑕
ዲ୰⌫ῶᑡ⑕
⾑ᑠᯈῶᑡ⑕
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟పୗ⑕
⫶⭠㞀ᐖ
౽⛎
ୗ⑩
ᝏᚰ
჎ྤ
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
↓ຊ⑕
⑂ປ
Ⓨ⇕
⮫ᗋ᳨ᰝ
⾑ᑠᯈᩘῶᑡ
௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ
㣗ḧῶ㏥
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ
㛵⠇③
➽⫗③
⚄⤒⣔㞀ᐖ
ᮎᲈᛶࢽ࣮ࣗࣟࣃࢳ࣮
㘒ឤぬ
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
⬺ẟ⑕
⓶⭵஝⇱
ࡑ࠺⑛⑕
Ⓨ⑈
ᩬ≧ୣ⑈≧⓶⑈
ᑜᖖᛶⓑᩬ
2 mg/kg Q3W⩌
178౛
඲Grades
Grades 3௨ୖ
121 (68.0)
20
(11.2)
౛ᩘ㸦%㸧
10 mg/kg Q3W⩌
179౛
඲Grades
Grades 3௨ୖ
133 (74.3)
25
(14.0)
ICC⩌
171౛
඲Grades
Grades 3௨ୖ
138 (80.7)
45
(26.3)
5
0
1
2
(2.8)
(0.0)
(0.6)
(1.1)
1
0
0
0
(0.6)
(0.0)
(0.0)
(0.0)
7
0
1
1
(3.9)
(0.0)
(0.6)
(0.6)
0
0
0
1
(0.0)
(0.0)
(0.0)
(0.6)
35
14
14
16
(20.5)
(8.2)
(8.2)
(9.4)
9
6
6
4
(5.3)
(3.5)
(3.5)
(2.3)
9
(5.1)
0
(0.0)
13
(7.3)
0
(0.0)
0
(0.0)
0
(0.0)
5
15
8
2
(2.8)
(8.4)
(4.5)
(1.1)
0
0
0
1
(0.0)
(0.0)
(0.0)
(0.6)
9
19
16
10
(5.0)
(10.6)
(8.9)
(5.6)
0
2
1
1
(0.0)
(1.1)
(0.6)
(0.6)
14
14
56
26
(8.2)
(8.2)
(32.7)
(15.2)
0
3
4
4
(0.0)
(1.8)
(2.3)
(2.3)
6
40
6
(3.4)
(22.5)
(3.4)
1
2
0
(0.6)
(1.1)
(0.0)
8
52
11
(4.5)
(29.1)
(6.1)
1
1
0
(0.6)
(0.6)
(0.0)
10
62
8
(5.8)
(36.3)
(4.7)
1
8
1
(0.6)
(4.7)
(0.6)
0
(0.0)
0
(0.0)
1
(0.6)
0
(0.0)
13
(7.6)
5
(2.9)
8
(4.5)
0
(0.0)
17
(9.5)
2
(1.1)
26
(15.2)
0
(0.0)
13
9
(7.3)
(5.1)
1
2
(0.6)
(1.1)
12
7
(6.7)
(3.9)
1
0
(0.6)
(0.0)
9
10
(5.3)
(5.8)
1
1
(0.6)
(0.6)
2
1
(1.1)
(0.6)
0
0
(0.0)
(0.0)
0
2
(0.0)
(1.1)
0
0
(0.0)
(0.0)
14
11
(8.2)
(6.4)
2
0
(1.2)
(0.0)
5
9
37
21
5
10
(2.8)
(5.1)
(20.8)
(11.8)
(2.8)
(5.6)
0
0
0
0
1
0
(0.0)
(0.0)
(0.0)
(0.0)
(0.6)
(0.0)
1
9
42
18
10
9
(0.6)
(5.0)
(23.5)
(10.1)
(5.6)
(5.0)
0
0
0
0
1
0
(0.0)
(0.0)
(0.0)
(0.0)
(0.6)
(0.0)
35
2
6
8
0
2
(20.5)
(1.2)
(3.5)
(4.7)
(0.0)
(1.2)
1
0
0
0
0
0
(0.6)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
࡞࠾ࠊ
2 mg/kg Q3W ⩌ཬࡧ 10 mg/kg Q3W ⩌࡟࠾࠸࡚ࡑࢀࡒࢀࠊ㛫㉁ᛶ⫵⑌ᝈ 1 ౛㸦0.6%㸧
ཬࡧ 4 ౛㸦2.2%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 1 ౛㸦0.6%㸧ཬࡧ 6 ౛㸦3.4%㸧ࠊ⚄⤒㞀ᐖ㸦ࢠ
࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧2 ౛㸦1.1%㸧ཬࡧ 0 ౛ࠊ⫢ᶵ⬟㞀ᐖ 13 ౛㸦7.3%㸧ཬࡧ 15 ౛㸦8.4%㸧ࠊ
⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧1 ౛㸦0.6%㸧ཬࡧ 1 ౛㸦0.6%㸧ࠊୗᆶయᶵ⬟㞀ᐖ 1
౛㸦0.6%㸧ཬࡧ 3 ౛㸦1.7%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ 14 ౛㸦7.9%㸧ཬࡧ 15 ౛㸦8.4%㸧ࠊinfusion
reaction 2 ౛㸦1.1%㸧ཬࡧ 3 ౛㸦1.7%㸧ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ⩌ࠊከᙧ⣚
ᩬࠊ㢮ኳ⑁⒔➼㸧1 ౛㸦0.6%㸧ཬࡧ 1 ౛㸦0.6%㸧ࠊ⮅⅖ 1 ౛㸦0.6%㸧ཬࡧ 0 ౛ࠊ㔜⑕➽
↓ຊ⑕ 0 ౛ཬࡧ 1 ౛㸦0.6%㸧ࠊ⬻⅖࣭㧊⭷⅖ 0 ౛ཬࡧ 1 ౛㸦0.6%㸧ࠊ୪ࡧ࡟ࡪ࡝࠺⭷
⅖ 0 ౛ཬࡧ 2 ౛㸦1.1%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ๪⭈㞀ᐖࠊ1 ᆺ⢾ᒀ⑓ࠊ➽⅖࣭ᶓ⣠➽⼥
ゎ⑕ཬࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
8
ճᾏእ➨Ϫ┦ヨ㦂㸦KEYNOTE-006 ヨ㦂㸧
᭷ᐖ஦㇟ࡣࠊ
10 mg/kg Q3W ⩌ 264/277 ౛
㸦95.3%㸧
ࠊ
10 mg/kg Q2W ⩌ 275/278 ౛
㸦98.9%㸧
ཬࡧ IPI ⩌ 239/256 ౛㸦93.4%㸧࡟ㄆࡵࡽࢀࠊ἞㦂⸆࡜ࡢᅉᯝ㛵ಀࡀྰᐃ࡛ࡁ࡞࠸᭷ᐖ஦
㇟ࡣࠊࡑࢀࡒࢀ 202/277 ౛㸦72.9%㸧ࠊ221/278 ౛㸦79.5%㸧ཬࡧ 187/256 ౛㸦73.0%㸧࡟
ㄆࡵࡽࢀࡓࠋ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝ࡣୗ⾲ࡢ࡜࠾ࡾ࡛࠶ࡗࡓࠋ
⾲ ࠸ࡎࢀ࠿ࡢ⩌࡛Ⓨ⌧⋡ࡀ 5%௨ୖࡢ๪స⏝㸦Ᏻ඲ᛶゎᯒᑐ㇟㞟ᅋ㸧
SOC
PT
㸦MedDRA ver.18.0㸧
඲๪స⏝
10 mg/kg Q3W⩌
277౛
඲Grades
Grades 3௨ୖ
202
(72.9) 28
(10.1)
౛ᩘ㸦%㸧
10 mg/kg Q2W⩌
278౛
඲Grades
Grades3௨ୖ
221 (79.5) 37
(13.3)
7
21
(2.5)
(7.6)
0
0
(0.0)
(0.0)
17
25
(6.1)
(9.0)
0
1
(0.0)
(0.4)
6
2
(2.3)
(0.8)
1
0
(0.4)
(0.0)
5
8
40
11
31
5
(1.8)
(2.9)
(14.4)
(4.0)
(11.2)
(1.8)
0
5
3
0
1
0
(0.0)
(1.8)
(1.1)
(0.0)
(0.4)
(0.0)
10
4
47
20
28
10
(3.6)
(1.4)
(16.9)
(7.2)
(10.1)
(3.6)
0
4
7
0
0
1
(0.0)
(1.4)
(2.5)
(0.0)
(0.0)
(0.4)
15
19
58
1
22
14
(5.9)
(7.4)
(22.7)
(0.4)
(8.6)
(5.5)
0
16
8
0
1
0
(0.0)
(6.3)
(3.1)
(0.0)
(0.4)
(0.0)
31
53
(11.2)
(19.1)
0
1
(0.0)
(0.4)
32
58
(11.5)
(20.9)
1
0
(0.4)
(0.0)
16
39
(6.3)
(15.2)
2
3
(0.8)
(1.2)
6
(2.2)
1
(0.4)
14
(5.0)
0
(0.0)
6
(2.3)
2
(0.8)
18
(6.5)
0
(0.0)
17
(6.1)
0
(0.0)
20
(7.8)
0
(0.0)
32
6
(11.6)
(2.2)
1
0
(0.4)
(0.0)
26
19
(9.4)
(6.8)
0
1
(0.0)
(0.4)
13
5
(5.1)
(2.0)
2
1
(0.8)
(0.4)
39
37
31
(14.1)
(13.4)
(11.2)
0
0
0
(0.0)
(0.0)
(0.0)
40
41
25
(14.4)
(14.7)
(9.0)
0
0
0
(0.0)
(0.0)
(0.0)
65
37
4
(25.4)
(14.5)
(1.6)
1
2
0
(0.4)
(0.8)
(0.0)
IPI⩌
256౛
඲Grades
Grades 3௨ୖ
187 (73.0) 51
(19.9)
ෆศἪ㞀ᐖ
⏥≧⭢ᶵ⬟ஹ㐍⑕
⏥≧⭢ᶵ⬟పୗ⑕
⫶⭠㞀ᐖ
⭡③
኱⭠⅖
ୗ⑩
ཱྀෆ஝⇱
ᝏᚰ
჎ྤ
୍⯡࣭඲㌟㞀ᐖ࠾ࡼࡧᢞ୚㒊఩ࡢ≧ែ
↓ຊ⑕
⑂ປ
⮫ᗋ᳨ᰝ
࢔ࢫࣃࣛࢠࣥ㓟࢔࣑ࣀࢺࣛࣥࢫࣇ࢙࣮ࣛࢮቑຍ
௦ㅰ࠾ࡼࡧᰤ㣴㞀ᐖ
㣗ḧῶ㏥
➽㦵᱁⣔࠾ࡼࡧ⤖ྜ⤌⧊㞀ᐖ
㛵⠇③
➽⫗③
⓶⭵࠾ࡼࡧ⓶ୗ⤌⧊㞀ᐖ
ࡑ࠺⑛⑕
⓶⑈
ᑜᖖᛶⓑᩬ
࡞࠾ࠊ
10 mg/kg Q3W ⩌ཬࡧ 10 mg/kg Q2W ⩌࡟࠾࠸࡚ࡑࢀࡒࢀࠊ㛫㉁ᛶ⫵⑌ᝈ 4 ౛㸦1.4%㸧
ཬࡧ 1 ౛㸦0.4%㸧ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ 10 ౛㸦3.6%㸧ཬࡧ 13 ౛㸦4.7%㸧ࠊ⚄⤒㞀ᐖ
㸦ࢠ࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧2 ౛㸦0.7%㸧ཬࡧ 0 ౛ࠊ⫢ᶵ⬟㞀ᐖ 14 ౛㸦5.1%㸧ཬࡧ 23
౛㸦8.3%㸧ࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶㛫㉁ᛶ⭈⅖➼㸧2 ౛㸦0.7%㸧ཬࡧ 1 ౛㸦0.4%㸧ࠊୗᆶ
యᶵ⬟㞀ᐖ 1 ౛㸦0.4%㸧ཬࡧ 1 ౛㸦0.4%㸧ࠊ⏥≧⭢ᶵ⬟㞀ᐖ 28 ౛㸦10.1%㸧ཬࡧ 33 ౛
㸦11.9%㸧ࠊ๪⭈㞀ᐖ 1 ౛㸦0.4%㸧ཬࡧ 2 ౛㸦0.7%㸧ࠊinfusion reaction 7 ౛㸦2.5%㸧ཬ
ࡧ 5 ౛㸦1.8%㸧ࠊ1 ᆺ⢾ᒀ⑓ 1 ౛㸦0.4%㸧ཬࡧ 0 ౛ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ
⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧0 ౛ཬࡧ 1 ౛㸦0.4%㸧ࠊ⮅⅖ 1 ౛㸦0.4%㸧ཬࡧ 1 ౛㸦0.4%㸧ࠊ
➽⅖࣭ᶓ⣠➽⼥ゎ⑕ 1 ౛㸦0.4%㸧ཬࡧ 0 ౛ࠊ⬻⅖࣭㧊⭷⅖ 0 ౛ཬࡧ 1 ౛㸦0.4%㸧ࠊ୪
ࡧ࡟ࡪ࡝࠺⭷⅖ 3 ౛㸦1.1%㸧ཬࡧ 1 ౛㸦0.4%㸧࡛ㄆࡵࡽࢀࡓࠋࡲࡓࠊ㔜⑕➽↓ຊ⑕ཬ
ࡧᚰ➽⅖ࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ
9
4㸬
㸬᪋タ࡟ࡘ࠸࡚
ᢎㄆ᮲௳࡜ࡋ࡚౑⏝ᡂ⦼ㄪᰝ㸦඲౛ㄪᰝ㸧ࡀㄢࡏࡽࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᙜヱㄪᰝࢆ㐺ษ
࡟ᐇ᪋࡛ࡁࡿ᪋タ࡛࠶ࡿᚲせࡀ࠶ࡿࠋࡑࡢୖ࡛ࠊᮏ๣ࡢᢞ୚ࡀ㐺ษ࡞ᝈ⪅ࢆデ᩿࣭≉ᐃ
ࡋࠊᮏ๣ࡢᢞ୚࡟ࡼࡾ㔜⠜࡞๪స⏝ࢆⓎ⌧ࡋࡓ㝿࡟ᑐᛂࡍࡿࡇ࡜ࡀᚲせ࡞ࡓࡵࠊ௨ୗࡢ
ձ㹼ճࡢࡍ࡭࡚ࢆ‶ࡓࡍ᪋タ࡟࠾࠸࡚౑⏝ࡍࡿ࡭ࡁ࡛࠶ࡿࠋ
ձ ᪋タ࡟ࡘ࠸࡚
ձ-1 ୗグࡢ㸦1㸧㹼㸦5㸧ࡢ࠸ࡎࢀ࠿࡟ヱᙜࡍࡿ᪋タ࡛࠶ࡿࡇ࡜ࠋ
(1) ཌ⏕ປാ኱⮧ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔➼㸦㒔㐨ᗓ┴ࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊ
ᆅᇦࡀࢇデ⒪㐃ᦠᣐⅬ⑓㝔ࠊᆅᇦࡀࢇデ⒪⑓㝔࡞࡝㸧㸦ᖹᡂ 28 ᖺ 10 ᭶ 1 ᪥᫬Ⅼ㸸
427 ᪋タ㸧
(2) ≉ᐃᶵ⬟⑓㝔㸦ᖹᡂ 28 ᖺ 9 ᭶ 1 ᪥᫬Ⅼ㸸84 ᪋タ㸧
(3) 㒔㐨ᗓ┴▱஦ࡀᣦᐃࡍࡿࡀࢇデ⒪㐃ᦠ⑓㝔㸦ࡀࢇデ⒪㐃ᦠᣦᐃ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ
༠ຊ⑓㝔ࠊࡀࢇデ⒪㐃ᦠ᥎㐍⑓㝔࡞࡝㸧
(4) እ᮶໬Ꮫ⒪ἲᐊࢆタ⨨ࡋࠊእ᮶໬Ꮫ⒪ἲຍ⟬ 1 ཪࡣእ᮶໬Ꮫ⒪ἲຍ⟬ 2 ࡢ᪋タᇶ‽
࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7 ᭶ 1 ᪥᫬Ⅼ㸸2538 ᪋タ㸧
(5) ᢠᝏᛶ⭘⒆๣ฎ᪉⟶⌮ຍ⟬ࡢ᪋タᇶ‽࡟ಀࡿᒆฟࢆ⾜ࡗ࡚࠸ࡿ᪋タ㸦ᖹᡂ 27 ᖺ 7
᭶ 1 ᪥᫬Ⅼ㸸1284 ᪋タ㸧
ձ-2 ᝏᛶ㯮Ⰽ⭘ࡢ໬Ꮫ⒪ἲཬࡧ๪స⏝Ⓨ⌧᫬ࡢᑐᛂ࡟༑ศ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ
㸦ୗ⾲ࡢ࠸ࡎࢀ࠿࡟ヱᙜࡍࡿ་ᖌ㸧ࡀࠊᙜヱデ⒪⛉ࡢᮏ๣࡟㛵ࡍࡿ἞⒪ࡢ㈐௵⪅࡜ࡋ࡚
㓄⨨ࡉࢀ࡚࠸ࡿࡇ࡜ࠋ
⾲
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 5 ᖺ௨ୖࡢࡀࢇ἞⒪ࡢ⮫ᗋ◊ಟࢆ
⾜ࡗ࡚࠸ࡿࡇ࡜ࠋ࠺ࡕࠊ2 ᖺ௨ୖࡣࠊࡀࢇ⸆≀⒪ἲࢆ୺࡜ࡋࡓ⮫ᗋ⭘⒆Ꮫࡢ◊ಟ
ࢆ⾜࡞ࡗ࡚࠸ࡿࡇ࡜ࠋ
y
་ᖌචチྲྀᚓᚋ 2 ᖺࡢึᮇ◊ಟࢆ⤊஢ࡋࡓᚋ࡟ 5 ᖺ௨ୖࡢ⓶⭵ᝏᛶ⭘⒆デ⒪ࡢ⮫
ᗋ⤒㦂ࢆ᭷ࡋ࡚࠸ࡿࡇ࡜ࠋ
ղ 㝔ෆࡢ་⸆ရ᝟ሗ⟶⌮ࡢయไ࡟ࡘ࠸࡚
་⸆ရ᝟ሗ⟶⌮࡟ᚑ஦ࡍࡿᑓ௵⪅ࡀ㓄⨨ࡉࢀࠊ〇⸆௻ᴗ࠿ࡽࡢ᝟ሗ❆ཱྀࠊ᭷ຠᛶ࣭Ᏻ඲
ᛶ➼⸆Ꮫⓗ᝟ሗࡢ⟶⌮ཬࡧ་ᖌ➼࡟ᑐࡍࡿ᝟ሗᥦ౪ࠊ᭷ᐖ஦㇟ࡀⓎ⏕ࡋࡓሙྜࡢሗ࿌ᴗ
ົࠊ➼ࡀ㏿ࡸ࠿࡟⾜ࢃࢀࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
10
ճ ๪స⏝࡬ࡢᑐᛂ࡟ࡘ࠸࡚
ճ-1 ๪స⏝Ⓨ⌧᫬ࡢᑐᛂయไ࡟㛵ࡍࡿせ௳
㛫㉁ᛶ⫵⑌ᝈ➼ࡢ㔜⠜࡞๪స⏝ࡀⓎ⏕ࡋࡓ㝿࡟ࠊ24 ᫬㛫デ⒪యไࡢୗࠊᙜヱ᪋タཪࡣ
㐃ᦠ᪋タ࡟࠾࠸࡚ࠊⓎ⌧ࡋࡓ๪స⏝࡟ᛂࡌ࡚ධ㝔⟶⌮ཬࡧ CT ➼ࡢ๪స⏝ࡢ㚷ู࡟ᚲせ
࡞᳨ᰝࡢ⤖ᯝࡀᙜ᪥୰࡟ᚓࡽࢀࠊ┤ࡕ࡟ᑐᛂྍ⬟࡞యไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
䐡-2 ་⒪ᚑ஦⪅࡟ࡼࡿ᭷ᐖ஦㇟ᑐᛂ࡟㛵ࡍࡿせ௳
ࡀࢇデ⒪࡟ᦠࢃࡿᑓ㛛ⓗ࡞▱㆑ཬࡧᢏ⬟ࢆ᭷ࡍࡿ་⒪ᚑ஦⪅ࡀ๪స⏝ࣔࢽࢱࣜࣥࢢࢆ
ྵࡵࡓⱞ③ࡢࢫࢡ࣮ࣜࢽࣥࢢࢆ⾜࠸୺἞་࡜᝟ሗࢆඹ᭷࡛ࡁࡿࢳ࣮࣒་⒪యไࡀᩚഛ
ࡉࢀ࡚࠸ࡿࡇ࡜ࠋ࡞࠾ࠊᩚഛయไ࡟ࡘ࠸࡚ࠊࡀࢇᝈ⪅࡜ࡑࡢᐙ᪘࡟༑ศ࡟࿘▱ࡉࢀ࡚࠸
ࡿࡇ࡜ࠋ
䐡-3 ๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚
๪స⏝㸦㛫㉁ᛶ⫵⑌ᝈ࡟ຍ࠼ࠊ኱⭠⅖࣭㔜ᗘࡢୗ⑩ࠊ⫢ᶵ⬟㞀ᐖࠊ⭈ᶵ⬟㞀ᐖ㸦ᒀ⣽⟶
㛫㉁ᛶ⭈⅖➼㸧ࠊෆศἪ㞀ᐖ㸦ୗᆶయᶵ⬟㞀ᐖࠊ⏥≧⭢ᶵ⬟㞀ᐖࠊ๪⭈ᶵ⬟㞀ᐖ㸧ࠊ1
ᆺ⢾ᒀ⑓ࠊࡪ࡝࠺⭷⅖ࠊ➽⅖࣭ᶓ⣠➽⼥ゎ⑕ࠊ⮅⅖ࠊ㔜ᗘࡢ⓶⭵㞀ᐖ㸦⓶⭵⢓⭷║⑕ೃ
⩌ࠊከᙧ⣚ᩬࠊ㢮ኳ⑁⒔➼㸧ࠊinfusion reactionࠊ⬻⅖࣭㧊⭷⅖ࠊ㔜⑕➽↓ຊ⑕ࠊ⚄⤒㞀
ᐖ㸦ࢠ࣭ࣛࣥࣂ࣮ࣞ⑕ೃ⩌➼㸧ࠊᚰ➽⅖➼㸧࡟ᑐࡋ࡚ࠊᙜヱ᪋タཪࡣ㏆㞄་⒪ᶵ㛵ࡢᑓ
㛛ᛶࢆ᭷ࡍࡿ་ᖌ࡜㐃ᦠࡋ㸦๪స⏝ࡢデ᩿ࡸᑐᛂ࡟㛵ࡋ࡚ᣦᑟཬࡧᨭ᥼ࢆཷࡅࡽࢀࡿ᮲
௳࡟࠶ࡿࡇ࡜㸧ࠊ┤ࡕ࡟㐺ษ࡞ฎ⨨ࡀ࡛ࡁࡿయไࡀᩚࡗ࡚࠸ࡿࡇ࡜ࠋ
11
5㸬
㸬ᢞ୚ᑐ㇟࡜࡞ࡿᝈ⪅
࠙Ᏻ඲ᛶࠚ
ձ ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣᮏ๣ࡢᢞ୚ࡀ⚗ᚷ࡜ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊᢞ୚ࢆ⾜
ࢃ࡞࠸ࡇ࡜ࠋ
y
ᮏ๣ࡢᡂศ࡟ᑐࡋ㐣ᩄ⑕ࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅
y
ዷ፬ཪࡣዷፎࡋ࡚࠸ࡿྍ⬟ᛶࡢ࠶ࡿᝈ⪅
ղ ἞⒪๓ࡢホ౯࡟࠾࠸࡚ୗグ࡟ヱᙜࡍࡿᝈ⪅࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢᢞ୚ࡣ᥎ዡࡉࢀ࡞࠸
ࡀࠊ௚ࡢ἞⒪㑅ᢥ⫥ࡀ࡞࠸ሙྜ࡟㝈ࡾࠊៅ㔜࡟ᮏ๣ࢆ౑⏝ࡍࡿࡇ࡜ࢆ⪃៖࡛ࡁࡿࠋ
y
㛫㉁ᛶ⫵⑌ᝈࡢྜేཪࡣ᪤ ࡢ࠶ࡿᝈ⪅
y
⬚㒊⏬ീ᳨ᰝ࡛㛫㉁ᙳࢆㄆࡵࡿᝈ⪅ཬࡧάືᛶࡢᨺᑕ⥺⫵⮚⅖ࡸឤᰁᛶ⫵⅖
➼ࡢ⫵࡟⅖⑕ᛶኚ໬ࡀࡳࡽࢀࡿᝈ⪅
y
⮬ᕫච␿⑌ᝈࡢྜేࠊཪࡣ៏ᛶⓗ࡞ⱝࡋࡃࡣ෌Ⓨᛶࡢ⮬ᕫච␿⑌ᝈࡢ᪤ Ṕࡢ
࠶ࡿᝈ⪅
y
ECOG Performance Status 3-4㸦ὀ1㸧ࡢᝈ⪅
࠙᭷ຠᛶࠚ
ձ ໬Ꮫ⒪ἲṔࡢ࡞࠸ᝈ⪅ཬࡧ໬Ꮫ⒪ἲṔࡢ࠶ࡿᝈ⪅࡟࠾࠸࡚ᮏ๣ࡢ᭷ຠᛶࡀ♧ࡉࢀ
࡚࠸ࡿࠋ
࡞࠾ࠊBRAF 㑇ఏᏊኚ␗ࢆ᭷ࡍࡿᝈ⪅࡟࠾࠸࡚ࡣࠊBRAF 㜼ᐖ๣࡟ࡼࡿ἞⒪ࡶ⪃៖
ࡍࡿࡇ࡜ࠋ
ղ ୗグ࡟ヱᙜࡍࡿᮏ๣ࡢᢞ୚ཬࡧ౑⏝᪉ἲ࡟ࡘ࠸࡚ࡣࠊᮏ๣ࡢ᭷ຠᛶࡀ☜❧ࡉࢀ࡚࠾
ࡽࡎࠊᮏ๣ࡢᢞ୚ᑐ㇟࡜࡞ࡽ࡞࠸ࠋ
y
⾡ᚋ⿵ຓ໬Ꮫ⒪ἲࠋ
y
௚ࡢᢠᝏᛶ⭘⒆๣࡜ࡢే⏝ࠋ
㸦ὀ1㸧
Score
0
1
2
3
4
ECOG ࡢ Performance Status㸦PS㸧
ᐃ⩏
඲ࡃၥ㢟࡞ࡃάື࡛ࡁࡿࠋⓎ⑓๓࡜ྠࡌ᪥ᖖ⏕άࡀไ㝈࡞ࡃ⾜࠼ࡿࠋ
⫗యⓗ࡟⃭ࡋ࠸άືࡣไ㝈ࡉࢀࡿࡀࠊṌ⾜ྍ⬟࡛ࠊ㍍సᴗࡸᗙࡗ࡚ࡢసᴗࡣ⾜࠺ࡇ࡜ࡀ࡛ࡁࡿࠋ
౛㸸㍍࠸ᐙ஦ࠊ஦ົసᴗ
Ṍ⾜ྍ⬟࡛⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣࡍ࡭࡚ྍ⬟ࡔࡀసᴗࡣ࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࡣ࣋ࢵࢻእ
࡛㐣ࡈࡍࠋ
㝈ࡽࢀࡓ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡋ࠿࡛ࡁ࡞࠸ࠋ᪥୰ࡢ 50%௨ୖࢆ࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
඲ࡃືࡅ࡞࠸ࠋ⮬ศࡢ㌟ࡢᅇࡾࡢࡇ࡜ࡣ඲ࡃ࡛ࡁ࡞࠸ࠋ᏶඲࡟࣋ࢵࢻ࠿᳔Ꮚ࡛㐣ࡈࡍࠋ
12
6㸬
㸬ᢞ୚࡟㝿ࡋ࡚␃ពࡍ࡭ࡁ஦㡯
ձ ῧ௜ᩥ᭩➼࡟ຍ࠼ࠊ〇㐀㈍኎ᴗ⪅ࡀᥦ౪ࡍࡿ㈨ᩱ➼࡟ᇶ࡙ࡁᮏ๣ࡢ≉ᛶཬࡧ㐺ṇ౑
⏝ࡢࡓࡵ࡟ᚲせ࡞᝟ሗࢆ༑ศ࡟⌮ゎࡋ࡚࠿ࡽ౑⏝ࡍࡿࡇ࡜ࠋ
ղ ἞⒪㛤ጞ࡟ඛ❧ࡕࠊᝈ⪅ཪࡣࡑࡢᐙ᪘࡟᭷ຠᛶཬࡧ༴㝤ᛶࢆ༑ศㄝ᫂ࡋࠊྠពࢆᚓ
࡚࠿ࡽᢞ୚ࡍࡿࡇ࡜ࠋ
ճ ୺࡞๪స⏝ࡢ࣐ࢿࢪ࣓ࣥࢺ࡟ࡘ࠸࡚
y
㛫㉁ᛶ⫵⑌ᝈࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚࡟࠶ࡓࡗ࡚ࡣࠊึᮇ⑕
≧㸦ᜥษࢀࠊ࿧྾ᅔ㞴ࠊတႿ➼㸧ࡢ☜ㄆཬࡧ⬚㒊 X ⥺᳨ᰝࡢᐇ᪋➼ࠊほᐹࢆ༑
ศ࡟⾜࠺ࡇ࡜ࠋࡲࡓࠊᚲせ࡟ᛂࡌ࡚⬚㒊 CTࠊ⾑Ύ࣐࣮࣮࢝➼ࡢ᳨ᰝࢆᐇ᪋ࡍ
ࡿࡇ࡜ࠋ
y
infusion reaction ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࠋinfusion reaction ࡀㄆࡵࡽࢀࡓሙྜ࡟
ࡣࠊ㐺ษ࡞ฎ⨨ࢆ⾜࠺࡜࡜ࡶ࡟ࠊ⑕≧ࡀᅇ᚟ࡍࡿࡲ࡛ᝈ⪅ࡢ≧ែࢆ༑ศ࡟ほᐹ
ࡍࡿࡇ࡜ࠋ
y
⏥≧⭢ᶵ⬟㞀ᐖࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚㛤ጞ๓ཬࡧᢞ୚ᮇ㛫
୰ࡣᐃᮇⓗ࡟⏥≧⭢ᶵ⬟᳨ᰝ㸦TSHࠊ㐟㞳 T3ࠊ㐟㞳 T4 ➼ࡢ ᐃ㸧ࢆᐇ᪋ࡍࡿ
ࡇ࡜ࠋ
y
⫢ᶵ⬟㞀ᐖࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᮏ๣ࡢᢞ୚㛤ጞ๓ཬࡧᢞ୚ᮇ㛫୰ࡣ
ᐃᮇⓗ࡟⫢ᶵ⬟᳨ᰝ㸦ASTࠊALTࠊγ-GTPࠊAl-Pࠊࣅࣜࣝࣅࣥ➼ࡢ ᐃ㸧ࢆᐇ᪋
ࡍࡿࡇ࡜ࠋ
y
ࡪ࡝࠺⭷⅖㸦⹿ᙬ⅖ཬࡧ⹿ᙬẟᵝయ⅖ࢆྵࡴ㸧➼ࡢ㔜⠜࡞║㞀ᐖࡀ࠶ࡽࢃࢀࡿ
ࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊᐃᮇⓗ࡟║ࡢ␗ᖖࡢ᭷↓ࢆ☜ㄆࡍࡿࡇ࡜ࠋࡲࡓࠊ║ࡢ␗ᖖࡀ
ㄆࡵࡽࢀࡓሙྜ࡟ࡣࠊ㏿ࡸ࠿࡟་⒪ᶵ㛵ࢆཷデࡍࡿࡼ࠺ᝈ⪅ࢆᣦᑟࡍࡿࡇ࡜ࠋ
y
ᮏ๣ࡢᢞ୚࡟ࡼࡾࠊ㐣ᗘࡢච␿཯ᛂ࡟㉳ᅉࡍࡿ࡜⪃࠼ࡽࢀࡿᵝࠎ࡞⑌ᝈࡸ⑓ែ
ࡀ࠶ࡽࢃࢀࡿࡇ࡜ࡀ࠶ࡿࠋ␗ᖖࡀㄆࡵࡽࢀࡓሙྜ࡟ࡣࠊⓎ⌧ࡋࡓ஦㇟࡟ᛂࡌࡓ
ᑓ㛛ⓗ࡞▱㆑࡜⤒㦂ࢆᣢࡘ་ᖌ࡜㐃ᦠࡋ࡚㐺ษ࡞㚷ูデ᩿ࢆ⾜࠸ࠊ㐣ᗘࡢච␿
཯ᛂ࡟ࡼࡿ๪స⏝ࡀ␲ࢃࢀࡿሙྜ࡟ࡣࠊᮏ๣ࡢఇ⸆ཪࡣ୰Ṇࠊཬࡧ๪⭈⓶㉁࣍
ࣝࣔࣥ๣ࡢᢞ୚➼ࢆ⪃៖ࡍࡿࡇ࡜ࠋ࡞࠾ࠊ๪⭈⓶㉁࣍ࣝࣔࣥࡢᢞ୚࡟ࡼࡾ๪స
⏝ࡢᨵၿࡀㄆࡵࡽࢀ࡞࠸ሙྜ࡟ࡣࠊ๪⭈⓶㉁࣍ࣝࣔࣥ௨እࡢච␿ᢚไ๣ࡢ㏣ຍ
ࡶ⪃៖ࡍࡿࡇ࡜ࠋ
y
ᢞ୚⤊஢ᚋࠊᩘ㐌㛫࠿ࡽᩘ࢝᭶⤒㐣ࡋ࡚࠿ࡽ๪స⏝ࡀⓎ⌧ࡍࡿࡇ࡜ࡀ࠶ࡿࡓࡵࠊ
ᮏ๣ࡢᢞ୚⤊஢ᚋ࡟ࡶ๪స⏝ࡢⓎ⌧࡟༑ศ࡟ὀពࡍࡿࡇ࡜ࠋ
y
1 ᆺ⢾ᒀ⑓㸦๻⑕ 1 ᆺ⢾ᒀ⑓ࢆྵࡴ㸧ࡀ࠶ࡽࢃࢀࠊ⢾ᒀ⑓ᛶࢣࢺ࢔ࢩࢻ࣮ࢩࢫ
࡟⮳ࡿࡇ࡜ࡀ࠶ࡿࡢ࡛ࠊཱྀῬࠊᝏᚰࠊ჎ྤ➼ࡢ⑕≧ࡢⓎ⌧ࡸ⾑⢾್ࡢୖ᪼࡟༑
ศὀពࡍࡿࡇ࡜ࠋ1 ᆺ⢾ᒀ⑓ࡀ␲ࢃࢀࡓሙྜ࡟ࡣᢞ୚ࢆ୰Ṇࡋࠊ࢖ࣥࢫࣜࣥ〇
๣ࡢᢞ୚➼ࡢ㐺ษ࡞ฎ⨨ࢆ⾜࠺ࡇ࡜ࠋ
մ ᮏ๣ࡢ⮫ᗋヨ㦂࡟࠾࠸࡚ࠊᢞ୚㛤ጞ࠿ࡽ 3 ࣨ᭶௨ෆࠊࡑࢀ௨㝆ࡣࠊᢞ୚㛤ጞ࠿ࡽ 1
ᖺ㛫ࡣ 6 㐌㛫ࡈ࡜࡟᭷ຠᛶࡢホ౯ࢆ⾜ࡗ࡚࠸ࡓࡇ࡜ࢆཧ⪃࡟ࠊᮏ๣ᢞ୚୰ࡣᐃᮇⓗ
࡟ຠᯝࡢ☜ㄆࢆ⾜࠺ࡇ࡜ࠋ
13

Download Report

（遺伝子組換え）製剤及びペムブロリズマブ（遺伝子組換え）

expydoc.com

Your ExpyDoc