blume 32, Issue 15S, Part | of II
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`;
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`May 20, 2014
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`»
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`OTE MecUnit mie Cs
`American Society of Clinical Oncology
`Journal ofclinical oncology : official journal of the
`oe
`American Society ofClinical Oncology.
`v.32, no.15, suppl. pt.1 (2014)
`General Collection
`W1 JO05894H
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`2014 ASCO Annual Meeting Proceedings
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`JOURNAL OF©
`CLINICAL
`ONCOLOGY
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`vRNA eRe Lae
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`SOth Annual Meeting
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`50th
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`Annual Meeting of the
`American Society of Clinical Oncology
`May 30-June 3, 2014
`
`Chicago, Illinois
`2014 Annual Meeting Proceedings Part|
`(a supplement to the Journalof Clinical Oncology)
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`ASC@
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`2)
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`Copyright 2014 American Society of Clinical Oncology
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`CONTENTS
`
`2014 ASCO ANNUAL MEETING PROCEEDINGS
`
`Special Award Lecture AbStractS ...ccccccccscccscscesssssssessssseccccessssecsecsnesccscsunseesessecseceestsacenececsvececseesenesenensens
`
`Plenary (Abstracts LBA1— LBA) cccccecccecssscssssesssssssssssesosssesesesessucesecosssnccecssesseesaceeneresseceecsansseaneseaceeseeeeasess
`Breast Cancer-HER2/ER
`Scheduled presentations (Abstracts 500 - TPSG72) cssssssesseesssscssessssnsssssnsronsartssereseseasenssesssseenssessesseseeseneates
`Breast Cancer-Triple-Negative/Cytotoxics/Local Therapy
`Scheduled presentations (AbstractS 1000% - TPS1149) .cssscssssserssnsseneenenstcsecsenesestsrersceestiesesciesenseaneseresevsceresiees
`Cancer Prevention/Epidemiology
`Scheduled presentations (AbstractS 1500 ~ TPS1G18) ....ssccssssssesssessssesrerseesseensartesssererentnseeensssessensessaseerseeseees
`Central Nervous System Tumors
`Scheduled presentations (Abstracts 2000 ~ TPS2112) ..sssssscccseenseessreestsneiseseneerensesnensetsenessctssenessessarenssseatsenss
`Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
`
`Scheduled presentations (Abstracts 2500 ~ TPS2647)wcrc
`ceseenseesentonecnerevsuseenseeeseneeeenseseee
`Developmental Therapeutics—immunotherapy
`Scheduled presentations (Abstracts 3000 - TPS3134) .s.sssssseecseseeceasseoeeseeesesstesenerereeneses
`Gastrointestinal (Colorectal) Cancer
`Scheduled presentations (AbstractS 3500 - TPS3667) ...ccsrscsseerennssnrssenensessrssesecsessensensessersstsssorseserseees
`Gastrointestinal (Noncoforectal) Cancer
`Scheduled presentations (AbstractS 4000 ~ TPS4163) ....-sceessccseserenenerssereesenensseeeseenseseatescssensesenssesenusserassus
`Genitourinary (Nonprostate) Cancer
`Scheduled presentations (Abstracts 4500 - TPS4607) ..ccsesesctcsseessessserensnessenssreneesssessesersessssssscssscensenestenes
`
`seeeetteeaees
`
`
`
`Is
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`35
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`5s
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`48s
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`84s
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`1145
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`1425
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`179s
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`2135s
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`255s
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`296s
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`continued on following page
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`Genitourinary (Prostate) Cancer
`Scheduled presentations (Abstracts 5000 - TPSSIN1) «.....seen cevsneeeeees veveeeneeteneceeneess veenecen deneneneseneeeeeneeees teense
`Gynecologic Cancer
`Scheduled presentations (Abstracts LBA5500 - TPS5632) ....-.... devseseceuseneeeees
`Head and Neck Cancer
`Scheduled presentations (Abstracts 6000 - TPS6106)......... veveneeneees sencssueccesevuneesaneeetaeccannensersrendaeevenaaeaeneeseneane
`Health Services Research
`Scheduled presentations (Abstracts 6500 - TPS6639) 0... cscs icc tenrrnecencanneieeteerscetettne eterno reas
`Leukemia, Myelodysplasia, and Transplantation
`Scheduled presentations (Abstracts 7002 - TPS7128) ........ vaeetenes presecantausensegenevaeeesaeveesteveesne peeeeventeneeneace veseeeee
`Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
`Scheduled presentations (Abstracts 7500 - TPS7612) o.oo seevecpusneseeesners peneersnees pugeeesesgeeaueeeereesee
`Lung Cancer-Non-Small Cell Metastatic
`Scheduled presentations (Abstracts 8000 - 8135) «1... Denne nevasevsnuaeeevseuneneses eeeeseees seeeeereseeneanenss vetnaneesenes
`Lymphomaand PlasmaCell Disorders
`Scheduled presentations (Abstracts 8500 - TPS8630) .......6 sereeccsaeeens deuneeeneerenesens seceeseteeneenaees sareeenneeatenoaee
`Melanoma/Skin Cancers
`Scheduled presentations (Abstracts LBA9000% - TPS9121) ......... svttedenetenennes
`Patient and Survivor Care
`Scheduled presentations (Abstracts LBA9500% - TPS9664) viteeesneenee veseeeee veceeeteeseusseseseneaeeeereneerens deeseenceeeeens
`Pediatric Oncology
`Scheduled presentations (Abstracts 10000 - TPS10095) vpepevsneseeccucceueeceesesstceassenseperses beveeeeeees Leeereeseneeegeeeeeee "
`
`
`
`Sarcoma
`Scheduled presentations (Abstracts 10500 - TPSIOGO4) ....... eee secs tene eerste etenecatteneeieceeeerersereenseeeen bevereeeres
`
`Tumor Biology
`Scheduled presentations (Abstracts M000 - TPS1N36) oo ccc ccce ets ee cette cree eesenenenserscaeeseasaneerasenseenyenene
`
`AUthor INGOX o..ccce ce ees ec ieaesee ne cesscesvenensacacusenareicinereeecsusecncassnensegnsasasacavetenanensseuganseasaciseseveneseneneere
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`nd
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`323s
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`351s
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`384s
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`410s
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`445s
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`477s
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`506s
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`539s
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`571s
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`695s
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`730s
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`

`

`Developmental Therapeutics—Immunotherapy
`
`
`This material maybe protected by Copyright law (Title 17 U.S. Code)
`
`
`
`
`180s
`
`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: | pilimumab-based immunotherapy has substantially increased
`survival for patients with advanced melanoma, however, the benefit
`is
`observedonly 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 nove! germline determinants of response to ipilimumab.
`Methods: Blood samples were collected from >60 metastatic melanoma
`patients treated 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 responsecriteria, using the
`Nextera platform (Iilumina) at average 30x coverage. We have implemented
`a novel modified methodfor testing the association between OR and NR by
`variant, gene and enrichmentof molecular networks. Gene-Set Enrichment
`Analysis and Pathway Studio were used to test the pathwayassociations.
`Results: The preliminary data comparing an initial subset of 30 ORs and 30
`NRs identified significant associations with ipilimumab response for
`several loci including RPS6KB1 (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 presenceof
`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 wil! further increase the analytical power of 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.
`
`Oral Abstract Session, Tue, 9:45 AM-12:45 PM
`3005“
`Clinical efficacy and correlation with tumor PD-L1 expression in patients
`(pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal anti-
`body MK-3475. Presenting Author: Richard Kefford, Westmead Hospital
`and MelanomaInstitute Australia, University of Sydney, Westmead, Austra-
`ia
`Background: MK-3475 demonstrated antitumor activity and acceptable
`safety in a phase | MEL cohort. We provide updated efficacy data and
`correlation with tumor PD-L1 expression. Methods: 135 pts received
`MK-3475 10 mg/kg Q2W (n = 57), 10 mg/kg Q3W (n = 56), or 2 me/kg
`Q3W (n = 22), Response was assessed every 12 wk by RECIST 1.1 by
`independentcentral review and by immune-related responsecriteria (irRC)
`by investigator. Biopsy was required in the 60 d before MK-3475. Tumor
`PD-L1 expression was assessed by IHC. A preliminary cutoff of 1% of
`stained tumorcells defined PD-L1 positivity. Results: As of 10/18/2013, all
`pts had =13 mofollow-up. Median time on treatment was 23 wk(range, 1
`dose to 97 wk). In 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 OSrate at 1 y was 81%. Tumor
`PD-L1 expression wasevaluable in 71 pts with measurable disease and =1
`tumor evaluation (77% PD-L1*)., Of these pts, PD-L1 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-L1* and
`69% in PD-L1- pts (P = .2146 [log-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 OS with acceptable
`safety in MEL. Although tumor PD-L1 positivity was associated with
`improved ORR and PFS, antitumoractivity was also observed in pts with
`low baseline PD-L1 expression. These preliminary data require confirma-
`tion. Clinical trial information: NCTO1295827.
`RECIST 1.1
`irre
`10034
`10 02W
`31
`49
`(18-47)
`(35-63)
`NR
`NR
`(11-724)
`(BF-76+)
`24
`50
`(12-36)
`(24-NR)
`4
`60
`
`Total
`4l
`(32-51)
`NR
`(BE-76+)
`31
`(19-50)
`53
`
`203W
`32
`(14-55)
`NR
`(9-604)
`72
`(12-NR)
`51
`
`10 QaW
`32
`{20-46)
`NR
`(11-65+)
`30
`(15-NR)
`54
`
`10 02W
`58
`(44-71)
`NR
`(12-934)
`84
`(24-NR}
`64
`
`Total
`43
`(35-52)
`NR
`(9-93+)
`54
`(24-NR)
`58
`
`ORR, %
`(95% Ch)
`Medlan response
`range’
`rations wh
`Median PFS,
`wh (95% Cl)
`24-wh PFS, %
`
`2034
`45
`(23-69)
`NR
`(9+ ~-604)
`72
`(12-NR)
`56
`
`Oral Abstract Session, Tue, 9:45 AM-12:45 PM
`3006°
`Evaluation of immune-related responsecriteria (irRC) in patients (pts) with
`advanced melanoma (MEL) treated with the anti-PD-1 monoclonal anti-
`body MK-3475. Presenting Author: F. Stephen Hodi, Dana-Farber Cancer
`Institute, Boston, MA
`Background: Unique response patterns have been observed with immuno-
`therapies, and both objective response and prolonged disease stabilization
`can occur after an initial increase in tumorsize. irRC were developed to
`better characterize response to immunotherapy, but it is unclear how irRC
`perform in pts treated with PD-1 blockade. Here, we describe unique
`patterns of response to MK-3475 in MEL pts and evaluate irRC as an
`alternative criterion for comprehensive response assessment. Methods:
`Source population was pts from 3 MEL cohorts treated with MK-3475 2
`me/kg every 3 wk (Q3W), 10 mg/kg Q3W,or 10 mg/kg Q2W in a phase |
`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. Tumorflareand atypical delayed response wereidentified by
`using centrally assessed irRC data among pts on MK-3475 for =28 wk.
`Tumorflare was defined as unconfirmed PD at assessment 1 (ie, wk 12) and
`non-PD at assessment2. Atypical delayed response was defined as PD at
`any time point followed by non-POD 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 asof the analysis cut-off of 10/18/2013, Tumorflare
`wasseen in 7 (3.6%) pts. In these pts, best overall response per irRC was
`CR (n = 1), PR (n = 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 byirRC
`had favorable OS compared with the 145 pts with PD by both criteria
`(Table). Conctusions: 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 responsecriteria that incorporate new
`data on PD-1 inhibitors may be appropriate for future consideration.
`Clinical trial information: NCTO01295827.
`
`Pts with CR/PR/SD by RECIST and irRC
`(n = 215)
`Pts with FD by RECIST but CR/PR/SDbyirRC
`(n=5
`Pts with PD by RECIST and irRC
`(n = 145)
`
`0S 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-4-1BB) in patients with advanced
`cancer. Presenting Author: Neil Howard Segal, Memorial Sloan Kettering
`Cancer Center, New York, NY
`Background: 4-1BB agonists markedly enhance cytotoxic T-cell responses,
`resulting in anti-tumoractivity in several models, PF-O5082566is a fully
`humanized |gG2 agonist monoclona! antibody targeting 4-1BB.This por-
`tion of thefirst-in-human phase | study assessed the safety, pharmacokinet-
`ics (PK), pharmacodynamics (PD) and antitumoractivity 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 3-6 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-05082566up 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 occurredto 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-O5082566 was well tolerated, with evidence of disease
`stabilization in multiple patients. Enroliment continues at higher dose
`levels to obtain additional safety, PK, PD, and efficacy data. Clinical trial
`information: NCTO1307267.
`
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