Jlume 32, Issue 158. Part | of" II
`
`Official Journal of the
`American Society of Clinical Oncology
`
`Journal of clinical oncology : official journal of the
`American Society of Clinical Oncology.
`v.32, no.15, suppl. pt.1 (2014)
`General Collection
`W1 305894H
`
`ASCQQ).
`
`50th Annual Meeting
`May 30-June 3. 2014
`McCormick Place
`Chicago. IL
`
`Genome & Co. v. Univ. of Chicago
`PG R201 9-00002
`
`UNIV. CHICAGO EX. 2054
`
`

`

`50th
`
`Annual Meeting of the
`
`American Society of Clinical Oncology
`
`May 30-June 3, 2014
`
`Chicago, Illinois
`
`2014 Annual Meeting Proceedings Part I
`
`(a supplement to the Journal of Clinical Oncology)
`
`
`ASCC,
`
`
` l
`
`Copyright 2014 American Society of Clinical Oncology
`
`

`

`Editor: Michael A. Carducci, MD
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`Managing Editor: Amy Hindman
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`céNTENTS
`
`2014 ASCO ANNUAL MEETING PROCEEDINGS
`
`Special Award LectureAbstracts 1s
`
`..........................................,.................................... ...... ..... .....
`35
`
`Plenary (Abstracts LBAl - LBA4)
`
`Breast Cancer—HERZ/ER
`Scheduled presentations (Abstracts 500 ' TP$672). 55
`
`Breast Cancer-Triple-Neqative/Cytotoxics/Local Therapy
`Scheduled presentations (Abstracts 1000" - TPSll49)
`
`.....
`
`Cancer Prevention/Epidemiology
`Scheduled presentations (Abstracts 1500 - TPS1618)
`
`Central Nervous System Tumors
`Scheduled presentations (Abstracts 2000 - TPSZlIZ)
`
`Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
`
`Scheduled presentations (Abstracts 2500 — TPS2647) ..
`
`Developmental Therapeutics-tmmunotherapy
`Scheduled presentations (Abstracts 3000 - TPS3134)
`
`Gastrointestinal (Colorectal) Cancer
`
`Scheduled presentations (Abstracts 3500 - TPS3667)
`
`Gastrointestinal (Noncolorectal) Cancer
`
`Scheduled presentations (Abstracts 4000 - TPS4163)
`
`Genitourinary (Nonprostate) Cancer
`Scheduled presentations (Abstracts 4500 - TPS4607)
`
`
`
`435
`
`84s
`
`1145
`
`1795
`
`2135
`
`2555
`
`2955
`
`continued on fol/o wing page
`
`
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`
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`‘
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`gUleEET.‘ Sfiiopgirtgitt Laws
`
`

`

`
`
`Genitourinary (Prostate) Cancer
`Schedmedpresentafions(Abshact55000-TPSSH1)”“hnuu ..... "n. ....... . .................... . ....... u. ................... .unn
`
`Gynecologic Cancer
`Scheduled presentations (Abstracts LBASSOO - TPS5632) ..........
`
`...... . ........
`
`
`
`Head and Neck Cancer
`Scheduled presentations (Abstracts 6000 - TPS6106) ......... . ...........
`
`............................................................
`
`Health Services Research
`Scheduled presentations (Abstracts 6500 - TPS6639) .....
`
`...... . ......................................................................
`
`Leukemia, Myelodysplasia, and Transplantation
`Schedubdinesentafions(Abshacts7002—-TPS7128). .......... i ........ . .............................................. . .................. . .......
`Lunq Cancer-Non-Small Cell Local-Reqional/Small Cell/Other Thoracic Cancers
`Scheduled presentations (Abstracts 7500 — TPS7612) .............................. . .......................
`....... r ........................
`
`Lunq Cancer-Non-Small Cell Metastatic
`Scheduled presentations (Abstracts 8000 — 8135) .................. .. ............................... . ........ . ......
`
`....... .. ...........
`
`Lymphoma and Plasma Cell Disorders
`Scheduled presentations (Abstracts 8500 - TP58630) ............... . ............. . ...... . ............ . ................. , .................
`
`3235
`
`35B
`
`3845
`
`4105
`
`4455
`
`477s
`
`506s
`
`5395
`
`Melanoma/Skin Cancers
`Scheduled presentations (Abstracts LBA9000" - TPS9121) ......... . .................
`
`
`
`5715
`
`Patient and Survivor Care
`SchedMedpresmfiafions(AbsUactsLBA9500A-TPS9664) .............. . ....... H ...... r ............................. . ..... tunnu
`
`Pediatric Oncology
`ScheduMdtnesentafions(Abshacts10000-TPS10095) ............................................... . .......... . ............ .......... "
`
`Sarcoma
`
`Scheduwdtnesentafions(Abshacts10500-TPS10604) ................................................................ . ...........
`
`Tumor Biology
`Scheduled presentations (Abstracts 11000 - TPS11136) ...................................................
`
`Author Index ...............................................................................................................................................
`
`6025
`
`6445
`
`6685
`
`6955
`
`7305
`
`

`

`l 805
`
`3004
`
`Oral Abstract Session, Tue, 9:45 AM-12:45 PM
`
`Germline genetic determinants of immunotherapy response in metastatic
`melanoma. Presenting Author: Christina Adaniel, New York University
`Medical Center, New York, NY
`
`Background: lpilimumab‘based immunotherapy has substantially increased
`survival for patients with advanced melanoma, however, the benefit
`is
`observed only in a small portion of treated patients. It is highly plausible,
`yet completely unexplored, that germline genetic factors modulate immuno-
`therapy outcome.
`in this study we performed whole-exome sequencing
`(WES) to discover novel germline determinants of response to ipilimumab.
`Methods: Blood samples were collected from >60 metastatic melanoma
`patientstreated by ipilimumab at the New York University Langone Medical
`Center. WES was performed on objective responders (OR) and non-
`responders (NR), defined by immune-related response criteria, using the
`Nextera platform (lllumina) at average 30x coverage. We have implemented
`a novel modified method for testing the association between OR and NR by
`variant, gene and enrichment of molecular networks. Gene-Set Enrichment
`Analysis and Pathway Studio were used to test the pathway associations.
`Results: The preliminary data comparing an initial subset of 30 ORs and 30
`NRs identified significant associations with ipilimumab response for
`several loci including RPS6KBl (p=0.001) and LNX2 (0.001). In addi-
`tion, the pathway analysis showed significant associations for SMAD 3
`(p=0.04) and interleukin 1
`(p=0.04) related pathways. Conclusions:
`Preliminary findings provide promising evidence supporting the presence of
`germline genetic factors associated with response to ipilimumab therapy
`and pointing to immune—related pathways associated with outcomes. As the
`study is still
`in progress,
`the anticipated accrual of a larger sample
`collection is underway. This will further increase the analytical powerof the
`discovery phase, but will also allow expanded validation of the current
`findings, suggesting for
`the first
`time that germline genetic factors
`modulate immunotherapy response.
`
`Developmental Therapeutics—lmmunotheropy
`
`This material may be protected by Copyright law (Title 17 us. Code)
`
`
`
`
`Oral Abstract Session, Tue, 9:45 AM-l 2:45 PM
`3005A
`Clinical efficacy and correlation with tumor PD-L1 expression in patients
`(pts) with melanoma (MEL) treated with the anti-PD-l monoclonal anti-
`body MK-3475. Presenting Author: Richard Kefford, Westmead Hospital
`ia
`and Melanoma Institute Australia, University of Sydney, Westmead, Austra-
`Background: MK~3475 demonstrated antitumor activity and acceptable
`safety in a phase l MEL cohort. We provide updated efficacy data and
`correlation with tumor PD-L1 expression. Methods: 135 pts received
`MK-3475 10 mg/kg 02W (n = 57), 10 mg/kg 03W (n = 56), or 2 mg/kg
`03W in = 22). Response was assessed every 12 wk by RECIST 1.1 by
`independent central review and by immune-related response criteria (irRC)
`by investigator. Biopsy was required in the 60 d before MK-3475. Tumor
`PD:L1 expression was assessed by lHC. A preliminaw cutoff of 1% of
`stained tumor cells defined PD-L1 positivity. Results: As of 10/18/2013, all
`pts had 213 me follow-up. Median time on treatment was 23 wk (range. 1
`dose to 97 wk). ln pts with measurable disease, ORR was 41% by RECIST
`(Table). Objective responses were observed as late as 64 wk, with some
`conversions to CR seen as late as 72 wk. Median response duration was not
`reached; responses were ongoing for 87% of responders. Median PFS was
`31 wk. Median OS was not reached, and 08 rate at 1 y was 81%. Tumor
`PD-L1 expression was evaluable in 71 pts with measurable disease and 21
`tumor evaluation (77% PD—L1*). Of these pts, PD-Ll expression was
`assoCIated with improved ORR by RECIST (51% vs 6%, P = .0012
`[Fisher’s exact]) and PFS (median 12 vs 3 mo, HR 0.31, 95% Cl
`0.16-0.61, P = .0004 [log-rank]). 1-y OS rate was 84% in PD-Ll+ and
`69% in PD-Ll‘ pts (P= .2146 [Iog-rank]). There were no treatment-related
`deaths; 14% of pts experienced drug-related grade 3/4 AEs. Conclusions:
`MK-3475 induces durable responses and favorable 1-y 08 with acceptable
`safety in MEL. Although tumor PD—L1 positivity was associated with
`improved ORR and PFS, antitumor activity was also observed in pts with
`low baseline PD-L1 expression. These preliminary data require confirma-
`tion. Clinical trial information: NCT01295827.
`RECIST Ll
`liRC
`in flaw
`in my
`31
`49
`(13.47)
`(35:53)
`NR
`NR
`(ll—72+)
`(Br-76¢)
`24
`50
`(12-36)
`(24-NR)
`44
`so
`
`Total
`41
`(32-51)
`NR
`(Br—76+)
`31
`(19:50)
`53
`
`2 mm
`32
`(IA-55)
`NR
`(9—60+)
`72
`(lZ-NR)
`51
`
`Total
`io uzw
`in inw
`43
`5a
`32
`(35-52)
`(44-71)
`(2045)
`NR
`NR
`NR
`(ll—65H (12-93“ (9-939)
`30
`34
`54
`(15~NR)
`(24an)
`(24-NR)
`54
`54
`58
`
`ORR-9%
`(95% CI)
`M'dllnrflponn
`range
`guratldn,“
`Medlln PFS.
`“(95%0)
`24-“ PFS. %
`
`2 new
`45
`(23759)
`NR
`Btu-600)
`72
`(12-NR)
`55
`
`3006A
`
`Oral Abstract Session, Tue, 9:45 AM-12:45 PM
`
`Evaluation of immune-related response criteria (irRC) in patients (pts) with
`advanced melanoma (MEL) treated With the anti-PD-l monoclonal anti-
`body MK-3475. Presenting Author: F. Stephen Hodi, Dana-Farber Cancer
`Institute, Boston, MA
`Background: Unique response patterns have been observed with immune-
`therapies, and both obiective response and prolonged disease stabilization
`can occur after an initial increase In tumor size.
`irRC were developed to
`better characterize response to immunotherapy, but it is unclear how irRC
`perform in pts treated With PD-l blockade. Here, we describe unique
`patterns of response to MK-3475 in. MEL pts and evaluate irRC as an
`alternative criterion for comprehenswe response assessment. Methods:
`Source population was pts from 3 MEL cohorts treated with MK—3475 2
`mg/kg every 3 wk_(Q3W), 10 mg/kg 03W, or 10 mg/kg 02W in a phase l
`trial. Tumor imaging was performed every 12 wk. Response was assessed
`by irRC and RECIST 1.1 by central
`review;
`irRC was used for pt
`management. Tumor flareland atypical delayed response were identified by
`using centrally assessed irRC data among pts on MK-3475 for :28 wk.
`Tumor flare was defined as unconfirmed PD at assessment 1 (ie, wk 12) and
`non-PD at assessment 2. Atypical delayed response was defined as PD at
`any time pomt followed by non-PD and then response. Survival data were
`analyzed in pts who had PD by RECIST but CR/PR/SD by irRC. Results:
`Among the 411 pts enrolled across the 3 MEL cohorts, 192 were on
`MK-3475 for :28 wk as of the analysis cut-off of 10/18/2013. Tumor flare
`was seen in 7 (3.6%) pts. In these pts, best overall response per irRC was
`CR (n = 1), PR in = 4), and SD (n = 2). Atypical delayed response was
`seen in 6 (3.1%) pts. The 51 pts With PD by RECIST but CR/PR/SD by irRC
`had favorable OS compared with the 145 pts with PD by both criteria
`(Table). Conclusions: MEL pts treated with MK-3475 may experience
`unique patterns of response and should be managed accordingly. Similar to
`what has been observed with ipilimumab, conventional criteria such as
`RECIST may underestimate the benefit of MK-3475 in approximately 10%
`of treated pts. An updated version of response criteria that incorporate new
`data on PD-l
`inhibitors may be appropriate for future consideration.
`Clinical trial information: NCT01295827.
`
`Pts with CR/PR/SD by RECIST and irRC
`(n = 215)
`(n = 5
`Pts with F1? by RECIST but CR/PR/SD by irRC
`Pts with PD by RECIST and irRC
`(n = 145)
`
`OS Rate
`6 mo
`
`98%
`
`94%
`53%
`
`3 mo
`
`100%
`
`100%
`79%
`
`12 mo
`
`92%
`
`67%
`34%
`
`Oral Abstract Session, Tue, 9:45 AM-12:45 PM
`3007
`A phase 1 study of PF-05082566 (anti-4-IBB) in patients with advanced
`cancer. Presenting Author: Neil Howard Segal, Memorial Sloan Kettering
`Cancer Center, New York, NY
`
`Background: 4-lBB agonists markedly enhance cytotoxic T-cell responses,
`resulting in anti-tumor activity in several models. PF-05082566 is a fully
`humanized lgG2 agonist monoclonal antibody targeting 4-lBB.This por-
`tion of the first-in-human phase I study assessed the safety, pharmacokinet-
`ics (PK), pharmacodynamics (PD) and antitumor activity of PF-0508256
`monotherapy in patients with advanced cancer. Methods: An open—label,
`dose escalation study was conducted in patients with advanced malignan-
`cies for which no curative therapy was available. Cohorts of 36 patients
`were enrolled initially using a 3+3 design (0.006 to 0.3 mg/kg), then a
`Time-To-Event CRM design for higher doses (0.6 to 5 mg/kg). Patients
`received PF-05082566 via intravenous infusion every 4 weeks (one cycle)
`with an 8 week period for assessment of dose-limiting toxicity (DLT).
`Radiographic assessments were conducted every 8 weeks, using RECIST
`1.1. Results: 27 patients have been treated with PF—05082566 up to the
`0.3 mg/kg dose level,
`including colorectal cancer (n=11), Merkel cell
`carcinoma (n=6), pancreatic adenocarcinoma (n=2), and one each of
`nasopharyngeal cancer, ampullary cancer, squamous cell
`lung cancer,
`carcinoma of unknown primary, melanoma, sarcoma, follicular lymphoma.
`and lymphocytic lymphoma (SLL). 25 patients completed the DLT assess-
`ment period and 7 patients remain on therapy. All discontinuations from
`treatment were due to disease progression. Median number of cycles
`ranged from 2 (at 0.006 mg/kg) to 7 (at 0.24 mg/kg). There was no
`apparent relationship between increasing doses and the frequency or
`severity of treatment emergent adverse events, which were mostly Grade 1.
`One patient treated at 0.06 mg/kg had Grade 3 elevation in alkaline
`phosphatase. No additional significant elevations in liver enzymes and no
`DLTs have occurred to date. Preliminary PK data suggests a linear increase
`in drug exposure with increasing dose, and a half life of ~10 days. A best
`overall response of stable disease was observed in 22% (6/27) patients.
`Conclusions: PF—05082566 was well tolerated, with evidence of disease
`stabilization in multiple patients. Enrollment continues at higher dose
`levels to obtain additional safety, PK, PD, and efficacy data. Clinical trial
`information: NCT01307267.
`
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