JP2017506227A - 癌治療のためのpd−1拮抗薬およびvegfr阻害剤の組み合わせ - Google Patents
癌治療のためのpd−1拮抗薬およびvegfr阻害剤の組み合わせ Download PDFInfo
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Abstract
Description
本出願は、2014年2月4日に出願した米国仮出願第61/935809号の全体を参考として援用しその優先権を主張する。
本出願は、ASCII形式で電子的に提出された配列表を含み、本明細書にその全体を参考として援用する。2015年1月29日に作成されたASCIIコピーは、PCFC-956-WO1_SL.txtと命名し、そのサイズは32535バイトである。
BID 一日二回1用量
CDR 相補性決定領域
CHO チャイニーズハムスター卵巣
DFS 無病生存
DTR 用量制限毒性
FFPE ホルマリン固定パラフィン包埋
FR フレームワーク領域
IgG 免疫グロブリンG
IHC 免疫組織化学または免疫組織化学的
MTD 最大耐用量
NCBI 米国国立生物工学情報センター
NCI 米国国立癌研究所
OR 総合的な奏功
OS 全生存期間
PD 進行性疾患
PFS 無増悪生存期間
PR 部分的奏功
Q2W 隔週1用量
Q3W 3週1用量
QD 1日1用量
RECIST 固形腫瘍効果判定基準
SD 安定な疾患
VH 免疫グロブリン重鎖可変領域
VK 免疫グロブリンκ軽鎖可変領
本発明がより容易に理解できるように、一定の技術用語および科学用語を、以下に具体的に定義する。本明細書のどこにも具体的に定義されなければ、本明細書で使用される他のすべての技術用語および科学用語は、本発明が属する技術分野の当業者によって理解される一般的な意味を有する。
MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERTHLVILGAILLCLGVALTFIFRLRKGRMMDVKKCGIQDTNSKKQSDTHLEET (配列番号25)
Md.)。
et al. (1975) Nature 256: 495、に記載されたハイブリドーマ法により、作製しても良く、また、または組換えDNA法(参照、例えば米国特許第4,816,567号)によって作製しても良い。「モノクローナル抗体」は、又、例えば、Clackson et al. (1991) Nature 352:
624-628、及びMarks et al. (1991) J. Mol. Biol. 222: 581-597、に記載された技術を用いてファージ抗体ライブラリーから単離しても良い。Presta (2005) J. Allergy Clin.
Immunol. 116:731.も又、参照のこと。
Thompson, R. H., et al., PNAS 101 (49); 17174-17179 (2004);
Thompson, R. H. et al., Cancer Res. 66:3381-3385 (2006);
Gadiot, J., et al., Cancer 117:2192-2201 (2011);
Taube, J. M. et al., Sci Transl Med 4, 127ra37 (2012);及び
Toplian, S. L. et al., New Eng. J Med. 366 (26): 2443-2454 (2012)。
本発明の一態様において、本発明は、個体における癌を治療するための方法を提供するものであり、PD-1拮抗薬およびVEGR阻害剤を含む併用療法で個体に投与することを含む。
Q3Wで投与し、そしてこの用量の組合せが患者に許容されない場合には、アキシチニブの用量を3 mg BID.に減量する。
1.PD-1拮抗薬及びVEGFR阻害剤を含む併用療法を個体に投与することを含む個体中の癌を治療する方法。
2.PD-1拮抗薬が、モノクローナル抗体、又はその抗原結合フラグメントである、実施態様1に記載の方法。
3.VEGFR阻害剤が化合物N- メチル-2- [3 -((E)-2- ピリジン-2- イル-ビニル)-1H-インダゾール-6-イルスルファニル] -ベンズアミドまたはその薬学的に許容される塩である、実施態様1または2に記載の方法。
4.個体中の癌を治療するためにVEGFR阻害剤と組み合わせて使用するPD-1拮抗薬を含む医薬であり、PD-1拮抗薬が、モノクローナル抗体、またはその抗原結合フラグメントである前記医薬。
5.個体中の癌を治療するためにPD-1拮抗薬と組み合わせて使用するVEGFR阻害剤を含む医薬。
6.薬学的に許容される賦形剤をさらに含む、実施態様4または5に記載の医薬。
7.個体中の癌を治療するため、VEGFR阻害剤と組み合わせて投与する時の医薬の製造における、PD-1拮抗薬の使用。
8.個体中の癌を治療するため、PD-1拮抗薬と組み合わせて投与する時の医薬の製造における、VEGFR阻害剤化合物の使用。
9.個体中の癌を治療するための医薬製造における、PD-1拮抗薬及びVEGFR阻害剤の使用。
10.第一容器、第二容器及びパッケージ挿入物を含むキットであり、第一容器は、少なくとも1用量の抗PD-1拮抗薬を含む医薬を含み、第二容器は、少なくとも1用量のVEGFR阻害剤を含む医薬を含み、及びパッケージ挿入物は、医薬を使用して個体の癌治療をするための使用説明書を含む。
11.使用説明書に、医薬は免疫組織化学(IHC)分析によるPD-L.1発現に関する検査が陽性である癌、を有する個体の治療に使用することを企図している、と明言している、実施態様10に記載のキット。
12.個体がヒトであり、かつPD-1拮抗薬がモノクローナル抗体であるか、又はその抗原結合フラグメントであり、具体的には、ヒトPD-L1に結合し、かつヒトPD-L1がヒトPD-1に結合するのをブロックする、実施態様1から11の何れかに記載の方法、医薬、使用又はキット。
13.PD-1拮抗薬がMPDL3280A、BMS-936559、MEDI4736、MSB0010718C又は重鎖及び軽鎖可変領域を含むモノクローナル抗体であり、これは、国際特許公開第2013/019906号にそれぞれ記載の配列番号24及び配列番号21である、実施態様11に記載の方法、医薬、使用又はキット。
14.個体はヒトであり、かつ、PD-1拮抗薬はモノクローナル抗体、であるか、又はその抗原結合フラグメントであり、具体的には、ヒトPD-1に結合し、かつヒトPD-L1がヒトPD-1に結合するのをブロックする、実施態様1から11の何れかに記載の方法、医薬、使用又はキット。
15.PD-1拮抗薬もまた、ヒトPD-L2がヒトPD-1に結合するのをブロックする、実施態様14に記載の、方法、医薬、使用又はキット。
16.モノクローナル抗体、又はその抗原結合フラグメントは、
(a)配列番号が1、2及び3である軽鎖CDR、及び配列番号が4、5及び6である、重鎖CDR、又は
(b)配列番号が7、8及び9である軽鎖CDR、及び配列番号が10、11及び12である重鎖CDR
を含む、実施態様15に記載の方法、医薬、使用又はキット。
17.モノクローナル抗体、又はその抗原結合フラグメントは、配列番号が7、8及び9である軽鎖CDR、及び配列番号が10、11及び12である重鎖CDRを含む、実施態様15に記載の方法、医薬、使用又はキット。
18.PD-1拮抗薬が、重鎖及び軽鎖を含む抗PD-1モノクローナル抗体であり、重鎖が、配列番号21であり、及び軽鎖が配列番号22である実施態様15に記載の方法、医薬、使用又はキット。
19.PD-1拮抗薬が、重鎖及び軽鎖を含む抗PD-1モノクローナル抗体であり、重鎖が、配列番号23であり、及び軽鎖が配列番号24である実施態様15に記載の方法、医薬、使用又はキット。
20.癌が固形腫瘍である実施態様12から19の何れかに記載の方法、医薬、使用又はキット。
21.癌が膀胱癌、乳癌、明細胞腎臓癌、頭部/頸部扁平上皮癌、肺扁平上皮癌、悪性黒色腫、非小細胞肺癌(NSCLC)、卵巣癌、膵臓癌、前立腺癌、腎細胞癌、小細胞肺癌(SCLC)又はトリプルネガティブ乳癌である、実施態様12から19の何れかに記載の方法、医薬、使用又はキット。
22.癌が、進行性腎細胞癌である、実施態様12から19の何れかに記載の方法、医薬、使用又はキット。
23.個体はそれ以前に進行性腎細胞癌の治療を受けたことがない、実施態様12から19の何れかに記載の方法、医薬、使用又はキット。
24.癌が、明細胞腎臓癌である、実施態様12から19の何れかに記載の方法、医薬、使用又はキット。
25.癌が、急性リンパ芽球性白血病(ALL)、急性骨髄性白血病(AML)、慢性リンパ球性白血病(CLL)、慢性骨髄性白血病(CML)、大規模びまん性B細胞リンパ腫(DLBCL)、濾胞性リンパ腫、ホジキンリンパ腫(HL)、マントル細胞リンパ腫(MCL)、多発性骨髄腫
(MM)、骨髄性細胞白血病-1タンパク質(MCL-1)、骨髄異形成症候群(MDS)、非ホジキンリンパ腫(NHL)、又は小リンパ球性リンパ腫(SLL)である、実施態様12から19の何れかに記載の方法、医薬、使用又はキット。
26.癌検査がヒトPD-L1に関し陽性である、実施態様12から25の何れかに記載の方法、医薬、使用又はキット。
27.ヒトPD-L1の発現が上昇している、実施態様26に記載の、方法、医薬、使用又はキット。
28.PD-1拮抗薬がMK-3475、又はニボルマブである、実施態様15に記載の、方法、医薬、使用又はキット。
29.MK-3475が、液体医薬として調剤され、pH 5.5のヒスチジン緩衝液10 mM中、MK-3475
25mg/ml、スクロース 7%(w / v)、ポリソルベート80 0.02%(w / v)を含む、実施態様28に記載の方法、医薬、使用又はキット。
30.VEGR阻害剤が、スニチニブ、ソラフェニブ又はチボザニブである、実施態様1から29の何れかに記載の方法、医薬、使用又はキット。
31.VEGR阻害剤が、N-メチル-2-[3-((E)-2-ピリジン-2-イル-ビニル)-1H-インダゾール-6-イルスルファニル]-ベンズアミド、又は薬学的に許容されるその塩である、実施態様1から29の何れかに記載の方法、医薬、使用又はキット。
32.VEFR阻害剤がアキシチニブで、かつ1mgの錠剤又は5mgの錠剤として調剤する、実施態様1から29の何れかに記載の方法、医薬、使用又はキット。
33.癌と診断されたヒト個体を治療する方法であり、(a)アキシチニブを5 mg BID用量で投与し、及びMK-3475を1 mg/kg Q3W, 2 mg/kg Q3W 及び 200 mg Q3Wからなる群から選択される用量で投与するか、又は(b)アキシチニブを、3 mg BID用量で投与し、及びMK-3475を1 mg/kg Q3W, 2 mg/kg Q3W 及び 200 mg Q3Wからなる群から選択される用量で投与する、MK-3475及びアキシチニブを含む併用療法、
を個体に投与することを含む前記ヒト個体を治療する方法。
34.MK-3475を含む医薬であり、ヒト個体における癌を治療するために、
(a)アキシチニブを5mgBID用量で、及びMK-3475を1 mg/kg Q3W, 2 mg/kg Q3W 及び 200 mg Q3Wからなる群から選択される用量で、又は、(b) アキシチニブを3 mg BID用量で、及びMK-3475を1 mg/kg Q3W, 2 mg/kg Q3W 及び 200 mg Q3Wからなる群から選択される用量で、個体に投与することを含む方法により、アキシチニブと組み合わせて使用するための前記医薬。
35.アキシチニブを含む医薬であり、ヒト個体の癌を治療するために、
(a)アキシチニブを5mgBID用量で、及びMK-3475を1 mg/kg Q3W, 2 mg/kg Q3W 及び 200 mg Q3Wからなる群から選択される用量で、又は、(b) アキシチニブを3 mg BID用量で、及びMK-3475を1 mg/kg Q3W, 2 mg/kg Q3W 及び 200 mg Q3Wからなる群から選択される用量で、個体に投与することを含む方法により、MK-3475と組み合わせて使用する前記医薬。
36.アキシチニブを5 mg BID の用量で投与し、かつ、MK-3475 を1 mg/kg Q3Wの用量で投与する、実施態様33から35の何れかに記載の方法又は医薬。
37.アキシチニブを5 mg BID の用量で投与し、かつ、MK-3475 を2 mg/kg Q3Wの用量で投与する、実施態様33から35の何れかに記載の方法又は医薬 。
38.アキシチニブを3 mg BID の用量で投与し、かつ、MK-3475 を1 mg/kg Q3Wの用量で 与する、実施態様33から35の何れかに記載の方法又は医薬。
39.アキシチニブを3 mg BID の用量で投与し、かつ、MK-3475 を2 mg/kg Q3Wの用量で 投与する、実施態様33から35の何れかに記載の方法又は医薬。
40.アキシチニブを3 mg BID の用量で投与し、かつ、MK-3475 を200 mg/kg Q3Wの用量で 投与する、実施態様33から35の何れかに記載の方法又は医薬。
41.癌が腎細胞癌である、実施態様33から40の何れかに記載の方法又は医薬 。
42.個体がそれ以前に腎細胞癌の治療を受けたことがない、実施態様41に記載の方法又は医薬。
43.癌が明細胞腎臓癌である、実施態様33から40の何れかに記載の方法又は医薬 。
44.併用療法の投与前に、個体から取り出した癌の組織切片の検査が、PD-L1の発現に関して陽性である、実施態様33から43の何れかに記載の方法又は医薬。
45.組織切片における腫瘍細胞の少なくとも50%が免疫組織化学(IHC)分析による検査でPD-L1発現に関して陽性である、実施態様44に記載の方法又は医薬。
46.IHC分析で抗体22C3を使用して、PD-L1の発現を検出する、実施態様45に記載の方法又は医薬。
47.MK-3475をIV注入によって投与する、33から46の何れかに記載の方法又は医薬 。
分子生物学における標準的な方法は、Sambrook, Fritsch and Maniatis (1982 & 1989 2nd Edition, 2001 3rdEdition) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NYS、ambrook and Russell (2001) Molecular Cloning, 3rd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Wu (1993) Recombinant DNA, Vol. 217, Academic Press, San Diego, CA)に記載されている。又、標準的方法がAusbel, et al. (2001) Current Protocols in Molecular Biology, Vols.1-4, John Wiley and Sons, Inc. New York, NY、にも見られ、細菌細胞およびDNA変異誘発におけるクローニング(第1巻)哺乳動物細胞および酵母におけるクローニング(第2巻)、複合糖質およびタンパク質発現(第3巻)、および生物情報科学(第4巻)について説明している。
New York, NY、を参照)。
この研究では、RCCを有するヒト患者におけるアキシチニブとMK-3475との組み合わせの有効性を評価する。患者をアキシチニブ5 mg BID又は3 mg BIDにより、及びMK-3475を1 mg/kg又は2 mg/kg、3週間毎に静脈内注入により、18ヶ月の期間、治療する。
研究対象年齢:18歳以上。
研究対象性別:両方。
健康なボランティアの受入れ:否
主に明細胞サブタイプを有する原発腫瘍であると組織学的または細胞学的に確定した進行性RCCを摘除する。
固形腫瘍における奏功評価基準(RECIST)バージョン1.1で定義された少なくとも一つの測定可能病変である。
東部共同腫瘍学グループの全身状態0または1; 及び、
高血圧は制御下にある。
1. Sharpe, A.H, Wherry, E.J., Ahmed R., and Freeman G.J. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nature Immunology (2007); 8:239-245.
2. Dong H et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002 Aug;8(8):793-800.
3. Yang et al. PD-1 interaction contributes to the functional suppression of T-cell responses to human uveal melanoma cells in vitro. Invest Ophthalmol Vis Sci. 2008 Jun;49(6 (2008): 49: 2518-2525.
4. Ghebeh et al. The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed
in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk propgnostic factors. Neoplasia (2006) 8: 190-198.
5. Hamanishi J et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proceeding of the National Academy of Sciences (2007): 104: 3360-3365.
6. Thompson RH et al. Significance of B7-H1 overexpression in kidney cancer. Clinical genitourin Cancer(2006): 5: 206-211.
7. Nomi, T. Sho, M., Akahori, T., et al. Clinical significance and therapeutic potential of the programmed death- 1 ligand/programmed death-1 pathway in human pancreatic cancer. Clinical Cancer Research (2007);13:2151-2157.
8. Ohigashi Y et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand 2 expression in human esophageal cancer. Clin. Cancer Research (2005): 11: 2947-2953.
9. Inman et al. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer (2007): 109: 1499-1505.
10. Shimauchi T et al. Augmented expression of programmed death-1 in both neoplasmatic and nonneoplastic CD4+ T-cells in adult T-cell Leukemia/ Lymphoma. Int. J. Cancer (2007): 121:2585-2590.
11. Gao et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clinical Cancer Research (2009) 15: 971-979.
12. Nakanishi J. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother. (2007) 56: 1173- 1182.
13. Hino et al. Tumor cell expression of programmed cell death-1 is a prognostic
factor for malignant melanoma. Cancer(2010): 00: 1-9.
14. Ghebeh H. Foxp3+ tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: implication for immunotherapy. BMC Cancer. 2008 Feb 23;8:57.
15. Ahmadzadeh M et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood(2009) 114: 1537-1544.
16. Thompson RH et al. PD-1 is expressed by tumor infiltrating cells and is associated with poor outcome for patients with renal carcinoma. Clinical Cancer Research(2007) 15: 1757-1761.
Claims (20)
- 個体中の癌を治療する方法であり、プログラム死1タンパク質(PD−1)の拮抗薬及びVEGFR阻害剤を含む併用療法を個体に投与することを含み、PD−1拮抗薬が、重鎖及び軽鎖を含む抗PD−1モノクローナル抗体であり、重鎖及び軽鎖は、それぞれ、配列番号21及び、配列番号22を含み、さらに、VEGFR阻害剤がN−メチル−2−[3−((E)−2−ピリジン−2−イル−ビニル)−1H−インダゾール−6−イルスルファニル]−ベンズアミドまたは薬学的に許容されるその塩である前記癌を治療する方法。
- 個体がヒトである、請求項1に記載の方法。
- 癌が固形腫瘍である、請求項1または2に記載の方法。
- 癌が腎細胞癌である、請求項1または2に記載の方法。
- PD−1拮抗薬が、MK−3475であり、かつVEGFR阻害剤がアキシチニブである、請求項1〜4の何れか1項に記載の方法。
- 個体中の癌を治療するため、VEGFR阻害剤と組み合わせて使う、プログラム死1タンパク質(PD−1)の拮抗薬を含む医薬であり、PD−1拮抗薬が、重鎖及び軽鎖を含む抗PD−1モノクローナル抗体であり、重鎖及び軽鎖は、それぞれ、配列番号21及び、配列番号22を含み、さらに、VEGFR阻害剤がN−メチル−2−[3−((E)−2−ピリジン−2−イル−ビニル)−1H−インダゾール−6−イルスルファニル]−ベンズアミドまたは薬学的に許容されるその塩である前記医薬。
- 個体中の癌を治療するため、プログラム死1タンパク質(PD−1)の拮抗薬と組み合わせて使う、VEGFR阻害剤を含む医薬であり、VEGFR阻害剤が、N−メチル−2−[3−((E)−2−ピリジン−2−イル−ビニル)−1H−インダゾール−6−イルスルファニル]−ベンズアミドまたは薬学的に許容されるその塩であり、更に、PD−1拮抗薬が、重鎖及び軽鎖を含む抗PD−1モノクローナル抗体であり、重鎖及び軽鎖は、それぞれ、配列番号21及び、配列番号22を含む前記医薬。
- 個体がヒトである、請求項6または7に記載の医薬。
- 癌が免疫組織化学分析によるPD−L.1の発現についての検査で陽性を示す固形腫瘍である、請求項6〜8の何れか1項に記載の医薬。
- 癌が腎細胞癌である、請求項6〜8の何れか1項に記載の医薬。
- PD−1拮抗薬がMK−3475であり、かつVEGFR阻害剤がアキシチニブである、請求項6〜10の何れか1項に記載の医薬。
- MK−3475が液体医薬として調剤され、pH5.5のヒスチジン緩衝液10mM中、MK−3475 25mg/ml、スクロース 7%(w/v)、ポリソルベート800.02%(w/v)を含み、かつアキシチニブは1mgの錠剤または5mgの錠剤として調剤される請求項11に記載の医薬。
- 第一容器、第二容器及びパッケージ挿入物を含むキットであり、第一容器は、プログラム死1タンパク質(PD−1)拮抗薬を含む少なくとも1用量の医薬を含み、第二容器は、VEGFR阻害剤を含む少なくとも1用量の医薬を含み、及びパッケージ挿入物は、医薬を使用して個体の癌治療をするための使用説明書を含み、ここで、PD−1拮抗薬は重鎖および軽鎖を含む抗PD−Iモノクローナル抗体であり、重鎖及び軽鎖はそれぞれ、配列番号21及び配列番号22を含み、更にVEGFR阻害剤は、N−メチル−2−[3−((E)−2−ピリジン−2−イル−ビニル)−1H−インダゾール−6−イルスルファニル]−ベンズアミドまたはその薬学的に許容される塩である前記キット。
- 使用説明書には、医薬は、免疫組織化学(IHC)解析によるPD−L.1発現に関する検査が陽性である癌、を有する個体の治療に使用することを企図していると明言している請求項13に記載のキット。
- 個体がヒトである請求項13または14に記載のキット。
- PD−1拮抗薬が、液体医薬として調剤したMK−3475であり、かつVEGFR阻害剤が、1mgの錠剤または5mgの錠剤として調剤したアキシチニブある請求項13〜15の何れか1項に記載のキット。
- 癌が膀胱癌、乳癌、明細胞腎臓癌、頭部/頸部扁平上皮癌、肺扁平上皮癌、悪性黒色腫、非小細胞肺癌(NSCLC)、卵巣癌、膵臓癌、前立腺癌、腎細胞癌、小細胞肺癌(SCLC)又はトリプルネガティブ乳癌、急性リンパ芽球性白血病(ALL)、急性骨髄性白血病(AML)、慢性リンパ球性白血病(CLL)、慢性骨髄性白血病(CML)、大規模びまん性B細胞リンパ腫(DLBCL)、濾胞性リンパ腫、ホジキンリンパ腫(HL)、マントル細胞リンパ腫(MCL)、多発性骨髄腫(MM)、骨髄性細胞白血病−1タンパク質(MCL−1)、骨髄異形成症候群(MDS)、非ホジキンリンパ腫(NHL)、又は小リンパ球性リンパ腫(SLL)である、請求項1〜3、請求項5〜9、または請求項11〜15の何れか1項に記載の方法、使用またはキット。
- 癌が進行性腎細胞癌である、請求項1〜17の何れか1項に記載の方法、使用またはキット。
- 癌と診断されたヒト個体を治療する方法であり、(a)アキシチニブを5mg BID用量で投与し、及びMK−3475を1mg/kg Q3W,2mg/kg Q3W及び200mg Q3Wからなる群から選択される用量で投与するか、又は(b)アキシチニブを、3mg BID用量で投与し、及びMK−3475を1mg/kg Q3W,2mg/kg Q3W及び200mg Q3Wからなる群から選択される用量で投与する、MK−3475及びアキシチニブを含む併用療法、を個体に投与することを含む前記ヒト個体を治療する方法。
(a)はアキシチニブは、5ミリグラムBIDおよびMK−3475の用量で投与される個体にMK−3475及びアキシチニブを含む併用療法を投与することを含む、癌と診断されたヒト個体に投与される治療するための方法1mg/kgのQ3Wからなる群から選択された用量での2mg/kgのQ3W及び200mg Q3Wまたは(b)アキシチニブは3ミリグラムBIDおよびMK−3475の用量で投与されるが、から選択された用量で投与される。1mg/kgでのQ3Wからなる群を2mg/kgのQ3W及び200mgのQ3W。 - (a)MK−3475を含む医薬を、アキシチニブと組み合わせて、ヒト個体における癌を治療するために、
(i)アキシチニブを5mgBID用量で、及びMK−3475を1mg/kg Q3W,2mg/kg Q3W及び200mg Q3Wからなる群から選択される用量で、又は、
(ii)アキシチニブを3mg BID用量で、及びMK−3475を1mg/kg Q3W,2mg/kg Q3W及び200mg Q3Wからなる群から選択される用量で、個体に投与することを含む方法により、使用するか、又は、
(b)アキシチニブを含む医薬を、MK−3475と組み合わせて、ヒト個体の癌を治療するために、
(i)アキシチニブを5mgBID用量で、及びMK−3475を1 mg/kg Q3W,2mg/kg Q3W及び200mg Q3Wからなる群から選択される用量で、又は、
(ii)アキシチニブを3mg BID用量で、及びMK−3475を1mg/kg Q3W,2mg/kg Q3W及び200mg Q3Wからなる群から選択される用量で、個体に投与することを含む方法により、MK−3475と組み合わせて使用する前記医薬。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020521786A (ja) * | 2017-06-02 | 2020-07-27 | バイエル・アクチエンゲゼルシヤフト | 癌治療のためのレゴラフェニブとpd−1/pd−l1(2)阻害剤の併用 |
Families Citing this family (76)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101586617B1 (ko) | 2007-06-18 | 2016-01-20 | 머크 샤프 앤 도메 비.브이. | 사람 프로그램된 사멸 수용체 pd-1에 대한 항체 |
EP3079699A4 (en) * | 2013-12-11 | 2017-07-19 | Glaxosmithkline LLC | Treating cancer with a combination of a pd-1 antagonist and a vegfr inhibitor |
LT3081576T (lt) | 2013-12-12 | 2019-10-25 | Shanghai hengrui pharmaceutical co ltd | Pd-1 antikūnas, antigeną surišantis jo fragmentas ir jų medicininis pritaikomumas |
TR201901507T4 (tr) | 2014-02-04 | 2019-02-21 | Merck Sharp & Dohme | Kanseri tedavi etmeye yönelik bir pd-1 antagonsitinin ve bir vegfr inhibitörünün kombinasyonu. |
US10899840B2 (en) | 2014-02-04 | 2021-01-26 | Pfizer Inc. | Combination of a PD-1 antagonist and a 4-1BB agonist for treating cancer |
JP2017507155A (ja) * | 2014-03-05 | 2017-03-16 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗pd−1抗体と他の抗癌剤の組合せを使用する腎癌の処置 |
CN107405401B (zh) | 2015-02-26 | 2022-02-01 | 默克专利股份公司 | 用于治疗癌症的pd-1/pd-l1抑制剂 |
ES2844799T3 (es) | 2015-04-17 | 2021-07-22 | Merck Sharp & Dohme | Biomarcadores sanguíneos de sensibilidad tumoral a antagonistas de PD-1 |
KR20180018762A (ko) | 2015-06-16 | 2018-02-21 | 메르크 파텐트 게엠베하 | Pd-l1 길항제 조합 치료 |
BR112018011781A2 (pt) | 2015-12-14 | 2018-12-04 | Macrogenics Inc | molécula biespecífica possuindo um ou mais sítios de ligação a epítopo capazes de ligação imunoespecífica a (um) epítopo(s) de pd-1 e um ou mais sítios de ligação a epítopo capazes de ligação imunoespecífica a (um) epítopo(s) de ctla-4, e composição farmacêutica |
CN105669864B (zh) | 2015-12-23 | 2018-10-16 | 杭州尚健生物技术有限公司 | 抗人程序性死亡受体1抗体及其制备方法和用途 |
CN107126563B (zh) * | 2016-02-26 | 2021-09-10 | 博生吉医药科技(苏州)有限公司 | 含低剂量阻断vegf信号通路的抗体的组合物及其用途 |
JP2019517549A (ja) * | 2016-06-10 | 2019-06-24 | ノバルティス アーゲー | C−raf阻害薬の治療的使用 |
WO2018044888A1 (en) * | 2016-08-29 | 2018-03-08 | Chen James C | Tumor vaccination systems, devices, and methods |
US20190233523A1 (en) * | 2016-09-26 | 2019-08-01 | Imclone Llc | Combination therapy for cancer |
EP3515495A4 (en) * | 2016-09-26 | 2020-08-26 | Ensemble Group Holdings | METHOD OF EVALUATION AND TREATMENT OF CANCER IN HUMANS WITH DYSREGULATED LYMPHATIC SYSTEMS |
BR112019006504A2 (pt) | 2016-10-06 | 2019-06-25 | Merck Patent Gmbh | regime de dosagem de avelumabe para o tratamento de câncer |
TWI764943B (zh) | 2016-10-10 | 2022-05-21 | 大陸商蘇州盛迪亞生物醫藥有限公司 | 一種抗pd-1抗體和vegfr抑制劑聯合在製備治療癌症的藥物中的用途 |
WO2018133842A1 (zh) | 2017-01-20 | 2018-07-26 | 大有华夏生物医药集团有限公司 | 人程序性死亡受体pd-1的单克隆抗体及其片段 |
KR20190134631A (ko) * | 2017-03-01 | 2019-12-04 | 제넨테크, 인크. | 암의 진단 및 치료 방법 |
BR112019018401A2 (pt) * | 2017-03-06 | 2020-04-07 | Merck Patent Gmbh | formulação aquosa de anticorpo anti-pd-l1 |
EP3600426A4 (en) * | 2017-03-31 | 2021-01-20 | Merck Sharp & Dohme Corp. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER WITH A COMBINATION OF A PD-1 ANTAGONIST AND AN ANTI-CTLA4 ANTIBODY |
CA3063201A1 (en) * | 2017-05-09 | 2018-11-15 | Tesaro, Inc. | Combination therapies for treating cancer |
CN106963948A (zh) * | 2017-05-12 | 2017-07-21 | 顾艳宏 | 阿帕替尼与Anti‑PD‑1抗体联用在制备结肠癌药物中的应用 |
MX2019013751A (es) | 2017-05-16 | 2020-01-15 | Jiangsu Hengrui Medicine Co | Composicion farmaceutica de anticuerpos del ligando 1 de muerte programada y su uso. |
WO2019032663A1 (en) * | 2017-08-09 | 2019-02-14 | Orionis Biosciences Inc. | PD-1 AND PD-L1 BINDING AGENTS |
WO2019067913A1 (en) * | 2017-09-29 | 2019-04-04 | Bristol-Myers Squibb Company | COMPOSITIONS AND METHODS OF TREATING CANCER |
BR112020006371A2 (pt) * | 2017-10-13 | 2020-09-29 | Merck Patent Gmbh | combinação de um inibidor de parp e um antagonista de ligação de eixo de pd-1 |
EP3707510B1 (en) | 2017-11-06 | 2024-06-26 | F. Hoffmann-La Roche AG | Diagnostic and therapeutic methods for cancer |
TW201922793A (zh) * | 2017-11-16 | 2019-06-16 | 大陸商江蘇恆瑞醫藥股份有限公司 | Pd-1抗體和vegfr抑制劑聯合治療小細胞肺癌的用途 |
TW201938165A (zh) * | 2017-12-18 | 2019-10-01 | 美商輝瑞股份有限公司 | 治療癌症的方法及組合療法 |
WO2019246110A1 (en) * | 2018-06-20 | 2019-12-26 | Incyte Corporation | Anti-pd-1 antibodies and uses thereof |
AU2019288728A1 (en) | 2018-06-23 | 2021-01-14 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor |
BR112021000673A2 (pt) | 2018-07-18 | 2021-04-20 | Genentech, Inc. | métodos para tratar um indivíduo com câncer de pulmão, kits, anticorpo anti-pd-l1 e composições |
WO2020015722A1 (en) * | 2018-07-19 | 2020-01-23 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Anti-pd-1 antibodies, dosages and uses thereof |
JP2021535169A (ja) | 2018-09-03 | 2021-12-16 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Teadモジュレーターとして有用なカルボキサミドおよびスルホンアミド誘導体 |
CN113196061A (zh) * | 2018-10-18 | 2021-07-30 | 豪夫迈·罗氏有限公司 | 肉瘤样肾癌的诊断和治疗方法 |
US20210388090A1 (en) * | 2018-10-31 | 2021-12-16 | Genentech, Inc. | Method and medicament for treating cancer unresponsive to pd-1/pd-l1 signaling inhibitor |
MX2021005189A (es) * | 2018-11-05 | 2022-01-18 | Aveo Pharmaceuticals Inc | Uso de tivozanib para tratar sujetos con cancer refractario. |
CN115120716A (zh) | 2019-01-14 | 2022-09-30 | 健泰科生物技术公司 | 用pd-1轴结合拮抗剂和rna疫苗治疗癌症的方法 |
CA3134522A1 (en) | 2019-04-19 | 2020-10-22 | Genentech, Inc. | Anti-mertk antibodies and their methods of use |
EP4058435A1 (en) | 2019-11-13 | 2022-09-21 | Genentech, Inc. | Therapeutic compounds and methods of use |
AU2021212197A1 (en) | 2020-01-31 | 2022-08-04 | BioNTech SE | Methods of inducing neoepitope-specific T cells with a PD-1 axis binding antagonist and an RNA vaccine |
CA3171563A1 (en) | 2020-03-25 | 2021-09-30 | Charles D. Blizzard | Ocular implant containing a tyrosine kinase inhibitor |
WO2022004760A1 (ja) | 2020-06-30 | 2022-01-06 | 塩野義製薬株式会社 | 抗ccr8抗体と化学療法剤の併用 |
US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
US20230321074A1 (en) | 2020-09-09 | 2023-10-12 | Shenzhen Chipscreen Biosciences, Co., Ltd. | Use of chiauranib in combination with immune checkpoint inhibitor in antitumor therapy |
AR123855A1 (es) | 2020-10-20 | 2023-01-18 | Genentech Inc | Anticuerpos anti-mertk conjugados con peg y métodos de uso |
WO2022093981A1 (en) | 2020-10-28 | 2022-05-05 | Genentech, Inc. | Combination therapy comprising ptpn22 inhibitors and pd-l1 binding antagonists |
WO2022098638A2 (en) | 2020-11-04 | 2022-05-12 | Genentech, Inc. | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies |
TW202225191A (zh) | 2020-11-04 | 2022-07-01 | 美商建南德克公司 | 抗cd20/抗cd3雙特異性抗體之皮下給藥 |
US20220153842A1 (en) | 2020-11-04 | 2022-05-19 | Genentech, Inc. | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies and anti-cd79b antibody drug conjugates |
CA3202523A1 (en) | 2020-12-02 | 2022-06-09 | Genentech, Inc. | Methods and compositions for neoadjuvant and adjuvant urothelial carcinoma therapy |
TW202243689A (zh) | 2021-04-30 | 2022-11-16 | 瑞士商赫孚孟拉羅股份公司 | 抗cd20/抗cd3雙特異性抗體及抗cd78b抗體藥物結合物的組合治療之給藥 |
EP4330436A1 (en) | 2021-04-30 | 2024-03-06 | Genentech, Inc. | Therapeutic and diagnostic methods and compositions for cancer |
CN115400115A (zh) * | 2021-05-26 | 2022-11-29 | 石药集团中奇制药技术(石家庄)有限公司 | 多西他赛白蛋白组合物和免疫检查点抑制剂的组合及用途 |
CA3223534A1 (en) | 2021-07-02 | 2023-01-05 | Genentech, Inc. | Methods and compositions for treating cancer |
CA3224180A1 (en) | 2021-07-28 | 2023-02-02 | F. Hoffmann-La Roche Ag | Methods and compositions for treating cancer |
EP4377350A2 (en) | 2021-07-28 | 2024-06-05 | Genentech, Inc. | Methods and compositions for treating cancer |
KR20230017756A (ko) * | 2021-07-28 | 2023-02-06 | 주식회사 티움바이오 | 종양 예방 또는 치료용 약학 조성물 및 이의 용도 |
WO2023056403A1 (en) | 2021-09-30 | 2023-04-06 | Genentech, Inc. | Methods for treatment of hematologic cancers using anti-tigit antibodies, anti-cd38 antibodies, and pd-1 axis binding antagonists |
WO2023080900A1 (en) | 2021-11-05 | 2023-05-11 | Genentech, Inc. | Methods and compositions for classifying and treating kidney cancer |
US20230202984A1 (en) | 2021-11-24 | 2023-06-29 | Genentech, Inc. | Therapeutic compounds and methods of use |
US20230203062A1 (en) | 2021-11-24 | 2023-06-29 | Genentech, Inc. | Therapeutic compounds and methods of use |
WO2023134787A2 (zh) * | 2022-01-14 | 2023-07-20 | 上海君实生物医药科技股份有限公司 | 抗pd-1抗体和抗vegf抗体组合在治疗肝细胞癌中的用途 |
WO2023167560A1 (ko) * | 2022-03-04 | 2023-09-07 | 주식회사 파노로스바이오사이언스 | Vegf-grab 및 pd-1 또는 pd-l1 길항제를 포함하는 병용 투여용 조성물 |
WO2023191816A1 (en) | 2022-04-01 | 2023-10-05 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2024015897A1 (en) | 2022-07-13 | 2024-01-18 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020432A1 (en) | 2022-07-19 | 2024-01-25 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024049949A1 (en) | 2022-09-01 | 2024-03-07 | Genentech, Inc. | Therapeutic and diagnostic methods for bladder cancer |
WO2024077095A1 (en) | 2022-10-05 | 2024-04-11 | Genentech, Inc. | Methods and compositions for classifying and treating bladder cancer |
WO2024077166A1 (en) | 2022-10-05 | 2024-04-11 | Genentech, Inc. | Methods and compositions for classifying and treating lung cancer |
WO2024091991A1 (en) | 2022-10-25 | 2024-05-02 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
WO2024137589A2 (en) | 2022-12-20 | 2024-06-27 | Genentech, Inc. | Methods of treating pancreatic cancer with a pd-1 axis binding antagonist and an rna vaccine |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006522087A (ja) * | 2003-04-03 | 2006-09-28 | ファイザー・インク | Ag013736を含んでなる剤形 |
WO2012135408A1 (en) * | 2011-03-31 | 2012-10-04 | Merck Sharp & Dohme Corp. | Stable formulations of antibodies to human programmed death receptor pd-1 and related treatments |
Family Cites Families (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
EP1135415B1 (en) | 1998-12-01 | 2010-08-11 | Facet Biotech Corporation | Humanized antibodies to gamma-interferon |
TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
US7141581B2 (en) | 1999-07-02 | 2006-11-28 | Agouron Pharmaceuticals, Inc. | Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use |
ES2654064T3 (es) | 2002-07-03 | 2024-03-13 | Ono Pharmaceutical Co | Composiciones inmunopotenciadoras que comprenden anticuerpos anti-PD-L1 |
US6778740B2 (en) * | 2002-07-31 | 2004-08-17 | Agilent Technologies, Inc. | Alignment of optical fiber elements |
ES2367430T3 (es) | 2002-12-23 | 2011-11-03 | Wyeth Llc | Anticuerpos contra pd-1 y sus usos. |
US7563869B2 (en) | 2003-01-23 | 2009-07-21 | Ono Pharmaceutical Co., Ltd. | Substance specific to human PD-1 |
CN101094836A (zh) | 2004-11-02 | 2007-12-26 | 辉瑞大药厂 | 制备吲唑化合物的方法 |
MX2007005273A (es) | 2004-11-02 | 2007-07-19 | Pfizer | Formas polimorficas de 6-[2-(metilcarbamoil)fenilsulfanil]-3- e-[2-(piridin-2-il)etenil]indazol. |
BRPI0518203A2 (pt) | 2004-11-02 | 2009-03-10 | Pfizer | mÉtodos para preparaÇço de compostos indazol |
WO2006048745A1 (en) | 2004-11-02 | 2006-05-11 | Pfizer Inc. | Methods for preparing indazole compounds |
CN101052633A (zh) | 2004-11-02 | 2007-10-10 | 辉瑞大药厂 | 制备吲唑化合物的方法 |
CN101213297B (zh) | 2005-05-09 | 2013-02-13 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及单独使用或与其它免疫治疗剂联合使用抗pd-1抗体来治疗癌症的方法 |
WO2006123223A1 (en) | 2005-05-19 | 2006-11-23 | Pfizer Inc. | Pharmaceutical compostions comprising an amorphous form of a vegf-r inhibitor |
KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
US20100055111A1 (en) * | 2007-02-14 | 2010-03-04 | Med. College Of Georgia Research Institute, Inc. | Indoleamine 2,3-dioxygenase, pd-1/pd-l pathways, and ctla4 pathways in the activation of regulatory t cells |
AU2008236444B2 (en) | 2007-04-05 | 2012-06-28 | Pfizer Products Inc. | Crystalline forms of 6- [2- (methylcarbamoyl) phenylsulfanyl] -3-E- [2- (pyridin-2-yl) ethenyl] indazole suitable for the treatment of abnormal cell growth in mammals |
KR101586617B1 (ko) | 2007-06-18 | 2016-01-20 | 머크 샤프 앤 도메 비.브이. | 사람 프로그램된 사멸 수용체 pd-1에 대한 항체 |
EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
CN102203125A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
MX349463B (es) | 2008-09-26 | 2017-07-31 | Univ Emory | Anticuerpos anti-pd-1, pd-l1 y pd-l2 humanos y usos de los mismos. |
PE20120341A1 (es) | 2008-12-09 | 2012-04-24 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t |
WO2011066342A2 (en) | 2009-11-24 | 2011-06-03 | Amplimmune, Inc. | Simultaneous inhibition of pd-l1/pd-l2 |
EP2545078A1 (en) | 2010-03-11 | 2013-01-16 | UCB Pharma, S.A. | Pd-1 antibody |
CN106432506A (zh) | 2011-05-24 | 2017-02-22 | 泽恩格尼亚股份有限公司 | 多价和单价多特异性复合物及其用途 |
EA026924B1 (ru) | 2011-08-01 | 2017-05-31 | Дженентек, Инк. | Способы лечения рака с использованием антагонистов, связывающихся с осью pd-1, и ингибиторов mek |
BR112014007163A2 (pt) | 2011-09-30 | 2017-04-04 | Pfizer | composições farmacêuticas de n-metil-2 [3 ((e)-2 piridin-2 il-vinil)-1h-indazol-6 ilsulfanil]-benzamida |
AU2012335254A1 (en) | 2011-11-11 | 2014-05-08 | Pfizer Inc. | N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide for the treatment of chronic myelogenous leukemia |
RU2737765C2 (ru) * | 2012-05-04 | 2020-12-02 | Пфайзер Инк. | Простатоассоциированные антигены и иммунотерапевтические схемы на основе вакцин |
SG11201407859YA (en) | 2012-05-31 | 2014-12-30 | Genentech Inc | Methods of treating cancer using pd-l1 axis binding antagonists and vegf antagonists |
US9682143B2 (en) * | 2012-08-14 | 2017-06-20 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
AR093984A1 (es) | 2012-12-21 | 2015-07-01 | Merck Sharp & Dohme | Anticuerpos que se unen a ligando 1 de muerte programada (pd-l1) humano |
WO2014163684A1 (en) | 2013-04-03 | 2014-10-09 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
WO2015069266A1 (en) | 2013-11-07 | 2015-05-14 | Flynn Daniel L | Methods for inhibiting tie2 kinase useful in the treatment of cancer |
US9457019B2 (en) | 2013-11-07 | 2016-10-04 | Deciphera Pharmaceuticals, Llc | Methods for inhibiting tie-2 kinase useful in the treatment of cancer |
CN112353943A (zh) | 2013-12-17 | 2021-02-12 | 豪夫迈·罗氏有限公司 | 用pd-1轴结合拮抗剂和紫杉烷治疗癌症的方法 |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
TR201901507T4 (tr) | 2014-02-04 | 2019-02-21 | Merck Sharp & Dohme | Kanseri tedavi etmeye yönelik bir pd-1 antagonsitinin ve bir vegfr inhibitörünün kombinasyonu. |
EP3107538B1 (en) | 2014-02-18 | 2020-05-27 | Health Research, Inc. | Combination therapy for hepatocellular carcinoma |
JP2017507155A (ja) | 2014-03-05 | 2017-03-16 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗pd−1抗体と他の抗癌剤の組合せを使用する腎癌の処置 |
EP3129377A4 (en) | 2014-04-11 | 2017-12-20 | The University of North Carolina at Chapel Hill | Mertk-specific pyrimidine compounds |
CA2949121A1 (en) | 2014-05-15 | 2015-11-19 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
US9539245B2 (en) | 2014-08-07 | 2017-01-10 | Aerpio Therapeutics, Inc. | Combination of immunotherapies with activators of Tie-2 |
WO2016040882A1 (en) | 2014-09-13 | 2016-03-17 | Novartis Ag | Combination therapies of egfr inhibitors |
EP3200775B1 (en) | 2014-10-03 | 2019-11-20 | Novartis AG | Combination therapies |
BR112017007379A2 (pt) | 2014-10-14 | 2017-12-19 | Dana Farber Cancer Inst Inc | moléculas de anticorpo para pd-l1 e usos das mesmas |
WO2016059602A2 (en) | 2014-10-16 | 2016-04-21 | Glaxo Group Limited | Methods of treating cancer and related compositions |
SG11201702723VA (en) | 2014-10-29 | 2017-05-30 | Five Prime Therapeutics Inc | Combination therapy for cancer |
GB201421647D0 (en) | 2014-12-05 | 2015-01-21 | Amcure Gmbh And Ruprecht-Karls-Universitat And Karlsruher Institut F�R Technologie | CD44v6-derived cyclic peptides for treating cancers and angiogenesis related diseases |
TWI595006B (zh) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗pd-1抗體類和使用彼等之方法 |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006522087A (ja) * | 2003-04-03 | 2006-09-28 | ファイザー・インク | Ag013736を含んでなる剤形 |
WO2012135408A1 (en) * | 2011-03-31 | 2012-10-04 | Merck Sharp & Dohme Corp. | Stable formulations of antibodies to human programmed death receptor pd-1 and related treatments |
Non-Patent Citations (4)
Title |
---|
ANONYMOUS: "NCT02014636 A PHASE I/II STUDY TO ASSESS THE SAFETY AND EFFICACY OF PAZOPANIB AND MK 3475 以下備考", CLINICAL TRIALS.GOV, JPN5017001124, 24 January 2014 (2014-01-24), pages 1 - 11, XP055180536, ISSN: 0003939400 * |
THE NEW ENGLAND JOURNAL OF MEDICINE, vol. 366, no. 26, JPN6018049396, 2012, pages 2443 - 2454, ISSN: 0003939402 * |
THE ONCOLOGIST, vol. 17, JPN6018049395, 2012, pages 1081 - 1089, ISSN: 0003939401 * |
YASUDA S; SHO M; YAMATO I; ET AL: "SIMULTANEOUS BLOCKADE OF PROGRAMMED DEATH 1 AND VASCULAR ENDOTHELIAL GROWTH FACTOR 以下備考", CLINICAL & EXPERIMENTAL IMMUNOLOGY, vol. VOL:172, NR:3, JPN5017001125, 18 April 2013 (2013-04-18), pages 500 - 506, ISSN: 0003939403 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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