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library.iaslc.org/conference-program?product_id=7&author=&category=&date=&session_type=Educational%20Session%7CExhibit%20Showcase%20Session%7CGrand%20Rounds%7CIASLC%20Business%20Meeting%20%7CIndustry%20Supported%20Symposium%7CJoint%20Session%20IASLC/CSCO/CAALC%7CMeet%20the%20Editor%7CMeet%20the%20Expert%7CMini%20Oral%7CMini%20Symposium%7COral%7CPlenary%20Session%7CPoster%20Session%20with%20Presenters%20Present&session=&presentation=&keyword=Peter%20Szlosarek&

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MA 19.05 - Pegylated Arginine Deiminase Potentiates PD-1/PD-L1 Immune Checkpoint Blockade in Malignant Mesothelioma

Peter Szlosarek, R. Khadeir, M. Sheaff, M. Locke, K. Lau, B. Wu, J. Bomalaski, S. Martin, S. Quezada

11:00 AM - 12:30 PM10/18/2017 ¤é¥»®É¶¡

Dr. Peter Szlosarek ¥i¥H¨ìBarts Cancer Institute

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·|­û¡Gmax yao10135972  µoªí®É¶¡:2017/9/8 ¤W¤È 08:00:02²Ä 501 ½g¦^À³
²{¦b¥Í§ÞªÑ²@µL¤H®ð³£¬O´X¦~«e³Q°ò¨È¯E¹©µ¹·dÃaªº¡CÂ÷®³Ãĵý³£ÁÙ¨S½T©w´N­J¶Ãª£§@¡Aöt¨ì¤»¡B¤C¦Ê¤¸¡A³Ì«á®`¦º¤@°ï§ë¸ê¤H¡C¥_·¥¬PÁöµM²{¦b¤]¤jº¦¤T­¿¤F¡A¦ýªÑ»ùÁÙ¦b80¤¸¤£·|¤ÓÂ÷ÃСA³o¼Ë¤ñ¸û°·±d¡C°U¦Ñ·¨¥S¤j¤O±ÀÂˤ§ºÖ¡A§Ú¤]¦b¤­¤Q´X¤¸¤J¤â¡A·P®¦¡C¦pªG¥_·¥¬P¥¼¨Ó¯à³Q°ª»ù¨ÖÁÊ¡A³o¹ï¥xÆW¥Í§Þ²£·~¤~¬O¦³¥Îªº±j¤ß°w¡I¤~·|±a°Ê¨ä¥L·sÃĪѦA¦¸¬¡Ä£¡C
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·|­û¡G¦Ñ´­10141055  µoªí®É¶¡:2017/9/7 ¤U¤È 10:44:15²Ä 500 ½g¦^À³
¦h»¡µL¯q¡A®ö¶O®É¶¡¡A¦U¦ì¯u¬P¤Í´N¦Û¤v¤À¿ë°²¬P¤Í©M»Ä«È­Ì§a¡I

·PÁÂÁÙÄ@·N«ùÄò¤£Â_¤À¨Éªº¯u¬P¤Í­Ì¡A¦³§A­Ì¯u¦n¡I

¼o¸Ü¤Ö»¡¡A¬Ý­«ÂI¨Ó¤F¡I

2017/07/24 Merck«Å§G¤F¤@­Ó´d¶Ëªº®ø®§

Merck (NYSE: MRK) announced that the pivotal phase 3 KEYNOTE-040 trial in previously

treated patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)

did not meet its pre-specified primary endpoint of overall survival (OS) (HR, 0.82

[95% CI, 0.67-1.01]; p = 0.03 [one-sided]).

¥Î©ó±ß´ÁÀYÀVÅ쪬²Ó­MÀù¤T´ÁÁ{§É¹êÅçOS©M¹ï·Ó²Õ©Ô¤£¶}¡Ap=0.03¡Aª`·NÁöµMp=0.03

¦ý¬O(HR, 0.82 [95% CI, 0.67-1.01]¡A©Ò¥H¥¢±Ñ¤F¡I

¡´Hazard ratioªº95% CI¥u­n¥]§t1(0.67-1.01¦³¨S¦³¥]§t1¡H¦³¡I)¡A¨â²Õ´N¨S¦³®t²§©Ê¡I

¡´¤£­n¥u·|¬Ýp value¡AÁÙ­n¾Ç·|¬ÝHR and mean difference!

«¢«¢~~¤p¤l­Ì¤SÁȨì¤F¡I¦AÁ¿¤U¥h§A­Ì³£¤ñ«Ü¦hÁ{§É¥DªvÂå®vÁÙ­n¼F®`¤F¡I

´Nºâ

2016/08/05 FDA¤~¥[³t§å­ã¤FKeynote-012ªºÁ{§É¸ÕÅç¼Æ¾Ú¡A¥Î©ó±ß´Áhead & neck SCCªº¤G½uªvÀø¡A

¦]¬°¦³®Ä²v16%¡A±µ¤U¨Óªºpivotal phase 3 KEYNOTE-040«o¥¢±Ñ¤F¡A¦³¨S¦³«ÜÀª§¼¡H

¨S¦³¡AMerck¤j¤èªº©Ó»{¥¢±Ñ¤F(¨S¦³»¡¬ì¾Ç¤Wªº¦¨¥\)¡I

¦ý¬O¡A¨ì¥Ø«e¬°¤îFDA¤]ÁÙ¨S¦³ºM¾P·íªìKeynote-012¹ïhead & neck SCCªº¾AÀ³¯g

Keynote 040, NCT02252042¦p¤U

-A randomized, multi-center, pivotal phase 3 study

-KEYTRUDA 200mg¨C3wks pk ¤T¿ï¤@ (methotrexate or docetaxel or cetuximab)

(methotrexate [40 mg/m2 on Days 1, 8, and 15 of each 3-week cycle],

docetaxel [75 mg/m2 on Day 1 of each 3-week cycle], or

cetuximab [400 mg/m2 loading dose on Day 1 and 250 mg/m2 IV on Days 8 and 15 of

Cycle 1], followed by cetuximab [250 mg/m2 on Days 1, 8, and 15 of each subsequent

3-week cycle])

-primary endpoint= OS;

-secondary endpoints= PFS and ORR

-November 2014¶}©l°µ,´¿±µ¨ü1-2¤ÆÀø¥¢±Ñªº495 patients

¦P¼Ë¬Oanti-PD1

¡´Keytruda°w¹ïHNSCCªº¤T´ÁÁ{§É¸ÕÅ祢±Ñ¤F(Keynote 040, NCT02252042, 2017/07/24)

¦ý¬O

¡´Opdivo°w¹ïHNSCCªº¤T´ÁÁ{§É¸ÕÅç(2016)«o¦¨¥\¤F(CheckMate 141, NCT02105636, 2016)

¡´Keytruda°w¹ïªÍÀù¤@½uªvÀøªºÁ{§É¦¨¥\¤F(Keynote 024, NCT02142738 2016 Oct)

Keytruda pk ¤ÆÀø

OS ([HR] 0.60; 95% [CI]: 0.41¡V0.89; p = .005)--¡´HRªº95% CI¦³¨S¦³¥]§t1¨S¦³¡I)

PFS (HR 0.50; 95% CI: 0.37¡V0.68; p < .001)--¡´HRªº95% CI¦³¨S¦³¥]§t1¨S¦³¡I)

¦ý¬O

¡´Opdivo°w¹ïªÍÀù¤@½uªvÀøªºÁ{§É«o¥¢±Ñ¤F(CheckMate 026, NCT02041533, 2017/06/28)

Opdivo pk ¤ÆÀø

-423¦W¥¼¸g¹LªvÀøªºNSCLC¡APD-L1 expression>=5%

-mPFS¡÷ Opdivo 4.2 months vs ¤ÆÀø5.9 months (HR 1.15; 95% [CI], 0.91 to 1.45; P = 0.25),

-mOS¡÷ Opdivo 14.4 months vs ¤ÆÀø13.2months (HR 1.02; 95% CI, 0.80 to 1.30).

-ORR¡÷ Opdivo 26% vs ¤ÆÀø 33%

°Æ§@¥Îany grade¡÷ Opdivo 71% vs ¤ÆÀø 92%

°Æ§@¥ÎGrade 3/4¡÷ Opdivo 18% vs ¤ÆÀø 51%

¦³¨S¦³·d¿ù¡H¨ãÅé­ì¦]¨ì©³¬O«ç¼Ë¡H¨S¦³¤H»¡ªº²M·¡¡I

¦]¬°PD-1/PD-L1¤W¥«¤~¤T¦~¡A¥þ¥@¬É³£ÁÙ¦b¬ã¨s¡I

¦b³o¨Ç¥¢±Ñªº¸gÅç©M±Ð°V¤§¤U¡A·Q·Q¬Ý¦pªG¥X²{¤@ºØ»²§U©ÊªºÃĪ«-AdI-PEG 20

Merck (anti PD-1-Keytruda)·|¤£·|«æ¤F¡H

Bristol-Myers Squibb (anti PD-1-Opdivo)·|¤£·|«æ¤F¡H

Roche (anti-PD-L1-Tecentriq)·|¤£·|«æ¤F¡H

Astrazeneca (anti-PD-L1-Imfinzi)·|¤£·|«æ¤F¡H

¤]·Q­n³v³ÀÀù¯gªvÀø¥«Ô·ªº¨ä¥L¤jÃļt·|¤£·|«æ¤F¡H

¦^ÂÐ¥»¤å ¦^¤W¥«Âd°Q½×°Ï1­¶
·|­û¡G¤@¤ô´H10144832  µoªí®É¶¡:2017/9/7 ¤U¤È 09:26:33²Ä 499 ½g¦^À³
»«¹£­ô¤j±ß¦w¡G

¤§«e°¸µMÅ¥¨ì¬Y¦ì§ë¸ê¤j¤j´£¨ì¡G¨S¦³¼z®Ú¡A¤]­n·|¸ò¡I

¤~¯à¦³©¯·f¤W¥_·¥¬P³o¯Z¶W°ª³t¦C¨®¡I

²Î­pªº¸ê®Æ¦pªG¯à´£¨Ñ¬P¤Í°Ñ¦Ò¡A¹ê¦b¬O¤H¥Í¤@¤j¼Ö¨Æ¡I

ºK¿ý¾ã²z¸ê®Æ¦p¤U¨Ñ°Ñ¡G

¡´¤é´Á¡´¦¨¥æªÑ¼Æ¡´¥þÅé¨é°Ó¨C¤é®w¦s¼W´îªÑ¼Æ¡´¥þÅé¨é°Ó¨C¤é®w¦sÁ`ªÑ¼Æ

¡´2016/02/15¡´2,840,096¡´1,609,861¡´1,609,861

¡´2016/02/16¡´1,080,261¡´370,036¡´1,979,897

-------------

¡´2017/08/01¡´2,246,744¡´458,480¡´28,932,479

-------------

¡´2017/08/31¡´506,952¡´45,250¡´31,639,839

¡´2017/09/01¡´882,097¡´112,915¡´31,752,754

¡´2017/09/04¡´1,813,196¡´189,858¡´31,942,612

¡´2017/09/05¡´2,523,988¡´126,332¡´32,068,944

¡´2017/09/06¡´1,876,558¡´65,239¡´32,134,183

¡´2017/09/07¡´1,567,664¡´114,576¡´32,248,759

¦^ÂÐ¥»¤å ¦^¤W¥«Âd°Q½×°Ï1­¶
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A phase 1/1B trial of ADI‐PEG 20 plus nab‐paclitaxel and gemcitabine in patients with

advanced pancreatic adenocarcinoma

DOI: 10.1002/cncr.30897, Received: February 23, 2017;

Revised: June 6, 2017; Accepted: June 12, 2017--------¬Ý¬Ý§r¡I¤@¦¸´N­×§ï¨ì©w¦ìªº¡A¥s°µ

¤j®v¡I²Ä¤@§@ªÌ©M³d¥ô§@ªÌ³£¬O±¾³o¦ìMaeve A. Lowery, MD, Gastrointestinal Oncology Service--

À³¸Ó¤ñ¸¯©|Ghassan K. Abou-Alfa, MD¹à¤@ÂI

Memorial Sloan Kettering Cancer Center----------¥xÆW¦h¤Ö¥Í§Þ¤½¥q·Q¦b³o¸Ì¶i¦æÁ{§É¹êÅç¦Ó¤£

¥i±o¡A¹ï¥_·¥¬P«o¬O®a±`«K¶º¤@¼Ë¡IÃø©ÇASCO, ESMO, AACR¥_·¥¬P³sÁ¿³£Ãi±oÁ¿¡I

Published online: Aug 18, 2017-----10¤Ñµoªíªº¡A²{¦b¤~Á¿¡I¦³°÷§C½Õªº¤½¥q¡A´«°µ¬O§O®a¡A

Accepted: June 12, 2017----³o¤Ñ´Nµo·s»D¡A·d¤£¦nÁÙ¶}°OªÌ·|¡Aµo§G­«°T«¨¡I

¯f¤H=18¦ìmetastatic pancreatic cancer, ECOG 0,1

´¿¸g±µ¨ü¹L1¦¸¨ä¥LªvÀøªº(dose-escalation cohort);

no prior treatment (expansion cohort)---¦ý¬O¦pªG·íªìªº¤ÆÀø¬O»²§U©Êªº¥BÀøµ{µ²§ô¶W¹L6­Ó¤ëªº¥i¥H¯Ç¤J

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gemcitabine (1000 mg/m2); nab-paclitaxel (125 mg/m2)--¨C¶g1¦¸¡A¨C¥|¶g¦@3¦¸

IM ADI-PEG 20 18 mg/m2 weekly (cohort 1, n=3)

IM ADI-PEG 20 36 mg/m2 weekly (cohort 2, n=6; expansion cohort, n=9)

primary endpoint= ¨M©wMTD(maximum tolerated dose) and RP2D (recommended phase 2 dose)

¬ã¨s´Á¶¡=November 2014~and September 2015

¸ê®Æ¤ÀªR®É¶¡=January 16, 2017-------¦¹®É³ºµMÁÙ¦³¤@¦ì¯f¤H¦b¥ÎADI-PEG 20(¦Ü¤Ö16¤ë~26­Ó¤ëÁÙ¬¡ªº¦n¦nªº)

3­Ó¯f¤H¦bcohort 1®É¨S¦³DLT(dose-limiting toxicities)µo¥Í¡A©Ò¥Hcohort 2ÅÜ6­Ó,¦³1/6 DLT

©Ò¥H«á¨Ó¨M©wMTD¬°36 mg/m2 weekly¡A¦A¦¬9­Ó¯f¤H(expansion phase)

°Æ§@¥Î= 18¦ì³£¦³grade 3/4; ³Ì±`µo¥Íªº¬°

neutropenia (12¦ì67%), leukopenia (10¦ì56%), anemia (8¦ì44%),lymphopenia (6¦ì33%)

¨S¦³µLªk­@¨üªº°Æ§@¥Îµo¥Í¡A¥B67%¥H¤Wªº°Æ§@¥Î³£¬Ogem+nab-pacªº°ÝÃD

PR=7/18(39%)

SD=10/18(56%)

NE=1/18

DCR=17/18(94.4%)

¥ÎRP2D(36 mg/m2 weekly)ªvÀøªº11¦ì¤¤---½×¤å¸Ì¦³«Üº}«Gªº¹Ï

PR=5/11(45.5%)--------(ÁY¤p80%ªº¦³¨â¦ì,¨ä¥Lªº³£¦³50%~55%ªºÁY¤p)(«ùÄòªº®É¶¡¦³24wks,32wks,48wks,80wks,¤@ª½«ùÄòªº)

SD=5/11(45.5%)--------(¤]³£¦³10%~25%ªºÁY¤p)

DCR=10/11(91%)

ORR=45.5% ----gem+nab-pac=23%----RECIST 1.1

mPFS= 6.1 months (95% CI, 5.3-11.2months)

mOS= 11.3 months (95% CI, 6.7 months to not reached)----gem+nab-pac=8.5months

¡´¥u¦³12/18­Ó¦³¥ý¨úsample¡A3/12¬°ASS deficiency

¡´SDªº¯f¤H¤¤ASS1-deficient and -proficientªº³£¦³

The median duration of arginine depletion to 10 microM

PRªº¯f¤H=16 wks (range 4~26wks)

SDªº¯f¤H=13 wks (range 2~30wks)

¡´ª½¨ì24wks¡÷median arginine levels remained suppressed & median citrulline levels remained elevated

¡´Anti¡VADI-PEG 20 antibodies were detectable in all patients by week 18

ª¾¹D³o¨â¶µ¦³¦h­«­n¶Ü¡H¦^ÀY¦A°á°á¥H«eªº¤å³¹´Nª¾¹D¤F¡I

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¬O¦]¬°ADI-PEG 20¥i¥H­°§C¦]gemcitabine-induced­±¹L«×½Õ¸`ªºRRM2---upregulation of RRM2(ribonucleotide reductase subunit M2)

Waiting for 2017/09/14¡÷adi+folfox

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