correction to: 33rd annual meeting & pre-conference ...correction open access correction to:...

CORRECTION Open Access

Correction to: 33rd Annual Meeting & Pre-Conference Programs of the Society forImmunotherapy of Cancer (SITC 2018)Sneha Berry1*, Nicolas Giraldo1, Peter Nguyen1, Benjamin Green1, Haiying Xu1, Aleksandra Ogurtsova1, Abha Soni1,Farah Succaria1, Daphne Wang1, Charles Roberts1, Julie Stein1, Elizabeth Engle1, Drew Pardoll1, Robert Anders1,Tricia Cottrell1, Janis M. Taube1, Ben Tran3, Mark Voskoboynik4, James Kuo5, Yung-Lue Bang6, Hyun-Cheo Chung7,Myung-Ju Ahn8, Sang-We Kim9, Ayesh Perera2, Daniel Freeman2, Ikbel Achour2, Raffaella Faggioni2, Feng Xiao2,Charles Ferte2*, Charlotte Lemech5, Funda Meric-Bernstam10*, Theresa Werner11, Stephen Hodi12,Wells Messersmith13, Nancy Lewis14, Craig Talluto15, Mirek Dostalek14, Aiyang Tao14, Sarah McWhirter16,Damian Trujillo16, Jason Luke17, Chunxiao Xu18, BoMarelli18, Jin Qi18, Guozhong Qin18, Huakui Yu18, Molly Jenkins18,Kin-Ming Lo18, Joern-Peter Halle18, Yan Lan18*, Matthew Taylor19*, Nicholas Vogelzang20, Allen Cohn20,Daniel Stepan21, Robert Shumaker21, Corina Dutcus21, Matthew Guo21, Emmett Schmidt22, Drew Rasco23,Marcia Brose24*, Nicholas Vogelzang25, Christopher Di Simone25, Sharad Jain25, Donald Richards25,Carlos Encarnacion25, Drew Rasco26, Robert Shumaker27, Corina Dutcus27, Daniel Stepan27, Matthew Guo27,Emmett Schmidt28, Matthew Taylor29, Nicholas Vogelzang30*, Carlos Encarnacion30, Allen Cohn30,Christopher Di Simone30, Drew Rasco31, Donald Richards30, Matthew Taylor32, Corina Dutcus33, Daniel Stepan33,Robert Shumaker33, Matthew Guo33, Emmett Schmidt34, James Mier35, Jeongshin An36*, Yeun-yeoul Yang36,Won-Hee Lee37, Jinho Yang37, Jong-kyu Kim36, Hyun Goo Kim36, Se Hyun Paek36, Jun Woo Lee36, Joohyun Woo36,Jong Bin Kim36, Hyungju Kwon36, Woosung Lim36, Nam Sun Paik36, Yoon-Keun Kim37, Byung-In Moon36,Filip Janku38*, David Tan39, Juan Martin-Liberal40, Shunji Takahashi41, Ravit Geva42, Ayca Gucalp43, Xueying Chen44,Kulandayan Subramanian45, Jennifer Mataraza45, Jennifer Wheler45 and Philippe Bedard46

Correction to: J Immuno Therapy Cancer. (2018) 6(Suppl 1)

https://doi.org/10.1186/s40425-018-0422-yhttps://doi.org/10.1186/s40425-018-0423-x

After publication of this supplement [1, 2], it wasbrought to our attention that due to an error authors

were either missing or incorrectly indicated as contrib-uting author while in fact they didn't contribute in thefollowing abstracts. In addition affiliations were listedwhere in fact there were no contributing authors affili-ated with them in the following abstracts. This has nowbeen included in this correction.

P128Multiplexed immunofluorescent assay developmentfor study of the PD-1/PD-L1 checkpoint in the tumorimmune microenvironment (TIME)

Sneha Berry, MS, Nicolas Giraldo, MD PhD, PeterNguyen, MS, Benjamin Green, BS, Haiying Xu, Aleksan-dra Ogurtsova, Abha Soni, DO, Farah Succaria, MD,Daphne Wang, MS, Charles Roberts, Julie Stein, MD,Elizabeth Engle, MSc, Drew Pardoll, MD, PhD, Robert

* Correspondence: [email protected]; [email protected];[email protected]; [email protected]; [email protected];[email protected]; [email protected];[email protected]; [email protected] Hopkins University School of Medicine, Baltimore, MD, USA2MedImmune, Gaithersburg, MD, USA10MD Anderson Cancer Center, Houston, TX, USA18EMD Serono Research and Development, Belmont, MA, USA19Oregon Health and Science University, Portland, OR, USA24Abramson Cancer Center of the University, Philadelphia, PA, USA30McKesson Specialty Health, Las Vegas, NV, USA36Ewha Womans University, Seoul, Korea, Republic of38MD Anderson Cancer Center, Houston, TX, USAFull list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Berry et al. Journal for ImmunoTherapy of Cancer (2019) 7:46 https://doi.org/10.1186/s40425-019-0519-y

http://crossmark.crossref.org/dialog/?doi=10.1186/s40425-019-0519-y&domain=pdf

mailto:[email protected]









http://creativecommons.org/licenses/by/4.0/

http://creativecommons.org/publicdomain/zero/1.0/

Anders, MD, PhD, Tricia Cottrell, MD, PhD, Janis M.Taube, MDJohns Hopkins University School of Medicine, Baltimore,MD, USA

Correspondence: Sneha Berry ([email protected])Journal for ImmunoTherapy of Cancer 2018, 6(Suppl1):P128

Janis M. Taube, MD is a contributing author and hastherefore been added to the author list in this correc-tion article. Contributing author Sneha Berry, MS islisted three times in the original article; this is nolonger the case in this correction article.

BackgroundMultispectral immunofluorescent (mIF) staining offormalin-fixed paraffin-embedded (FFPE) tissue allowsspatially-resolved quantitative analysis of cell positionand protein expression. The design and validation ofmIF panels is a challenge. Our goal was to develop a7-plex assay for characterizing PD-1 and PD-L1 expres-sion, with high sensitivity for multiple markers and min-imal bleed-through between fluorescent channels, whileavoiding steric hindrance among markers occupying thesame cellular compartment.

MethodsSingle IF slides were stained for PD-1, PD-L1, CD8,FoxP3, CD163, and a tumor marker (e.g. Sox10/S100 formelanoma) using primary antibodies at manufacturer’srecommended concentrations and visualized with an Opalkit (PerkinElmer). Positive signal was compared tochromogenic IHC (n=3 tonsil specimens). In some in-stances, the kit’s HRP-polymer was substituted for onethat provided greater amplification. Primary antibody ti-trations were performed, and the concentration with com-parable signal to chromogenic IHC that showed thehighest IF signal to noise ratio was selected. Using the se-lected primary antibody concentration, TSA dilution serieswere performed on n=5 tumor specimens to minimizebleed-through. Finally, the optimized single IF stains werecombined into multiplex format, which was again vali-dated to ensure no positivity loss. Images were scannedwith the Vectra 3.0 and processed using inForm (Ver 2.3).

ResultsThe percent positive pixels for CD163, CD8, and tumormarker expression by IF were comparable to chromo-genic IHC with manufacturer’s recommended protocols(p>0.05). However, PD-1, PD-L1, and FoxP3 showed~50% loss of signal (p<0.05), which was recovered by re-placing the Opal kit's secondary HRP polymer withPowerVision (Leica). Unbalanced fluorescence intensities

between 540 to 570 Opal dyes resulted in significantbleed-through and led to false positive pixels. This errorwas minimized >2 fold (2.5% to 1.1%) by concentratingthe 570 dye and ensuring that this dye pair was used tostudy markers in different cellular compartments (nu-clear FoxP3 vs. membrane CD8), so any residualbleed-through could be discounted during image ana-lysis. Using the optimized panel, we are able to reliablyidentify cell types contributing PD-L1 and PD-1 to theTIME, and even resolve populations of PD-1high vs.PD-1low lymphocytes.

ConclusionsWe demonstrate successful optimization of a 7-colormultiplex panel characterizing the PD-1/PD-L1 axis toprovide high quality data sets for whole slide or regionalanalysis of the TIME. With the use of multiparametricassays such as this, we hope to guide improved ap-proaches to patient selection and potentially identifyadditional tumor types likely to respond to anti-PD-(L)1immunotherapy.

Ethics ApprovalThe study was approved by Johns Hopkins UniversityInstitutional Review Board.

P308A Phase 1 study of MEDI5752, a bispecific antibodythat preferentially targets PD-1 and CTLA-4 express-ing T cells, in patients with advanced solid tumors

Ben Tran2, Mark Voskoboynik3, James Kuo4, Yung-LueBang5, Hyun-Cheo Chung6, Myung-Ju Ahn7, Sang-WeKim8, Ayesh Perera1, Daniel Freeman1, Ikbel Achour1,Raffaella Faggioni1, Feng Xiao1, Charles Ferte1, CharlotteLemech4

1MedImmune, Gaithersburg, MD, USA; 2PeterMacCallum Cancer Center, Melbourne, Australia;3Nucleus Network, Melbourne, Australia; 4ScientiaClinical Research, Sydney, Australia; 5Seoul NationalUniversity Hospital, Seoul, Korea, Republic of;6Yonsei Cancer Center, Yonsei University, Seoul,Korea, Republic of; 7Samsung Medical Center, Seoul,Korea, Republic of; 8Asan Medical Center, Songpa-Gu,Korea, Republic of

Correspondence: Charles Ferte ([email protected]) Journal for ImmunoTherapy of Cancer 2018,6(Suppl 1):P308

Jeff Brubaker was not a contributing author and hastherefore been removed from the author list in thiscorrection article. The credentials as shown on the

Berry et al. Journal for ImmunoTherapy of Cancer (2019) 7:46 of 11

original article are no longer listed on this correctionarticle.

BackgroundBased on demonstrated clinical activity and manageablesafety profiles, checkpoint inhibiting antibodies block-ing PD 1, PD-L1, or CTLA-4 have received regulatoryapprovals for the treatment of various malignancies[1-5]. The combination therapy with anti-PD-1 andanti-CTLA-4 agents is approved by FDA for metastaticmelanoma, renal cell carcinoma and microsatelliteinstability-high (MSI-H) or mismatch repair deficient(dMMR) metastatic colorectal cancer, based on im-proved overall survival versus either agent alone [6-10].Numerous clinical studies of combination immunother-apy are currently investigating the same combinationacross a range of solid tumors [11- 15]. Although theefficacy of these drug combinations is dose dependent,the toxicity associated with anti-CTLA-4 agents, in par-ticular, is dose limiting, thereby potentially affecting treat-ment outcomes with combination therapy.- MEDI5752 isa bispecific humanized IgG1 monoclonal antibody thatbinds PD-1 and CTLA-4. In contrast to the combinationtherapy, MEDI5752 exhibits a novel T cell targetingmechanism that could provide a favorable toxicityprofile. In addition, we have shown that MEDI5752can impact cell surface expression of PD-1. Based onthese novel mechanisms of action, MEDI5752 mayshow improved efficacy and safety in comparison toco- administration of conventional anti-PD1/anti-PD-L1 and anti-CTLA-4 antibodies.

MethodsThis is a Phase 1, first-time-in-human, multicenter,open-label study in patients with advanced solidtumors. The dose-escalation phase will evaluate ap-proximately six MEDI5752 dose levels to identify amaximum tolerated dose. Dose escalation will befollowed by two dose-expansion cohorts in definedsetting with patients with advanced or metastaticsolid tumor and tested against a control arm. Subjectswill remain on treatment until confirmed progressivedisease, initiation of alternative cancer therapy, un-acceptable toxicity, or other reason for discontinu-ation. The primary endpoints are safety and efficacy(objective response in the dose-expansion phase).Secondary endpoints include additional efficacy as-sessment across both phases, pharmacokinetics, andimmunogenicity.

Trial RegistrationNCT03530397

References1. Opdivo Prescribing Information. Princeton, NJ: Bristol-Myers Squibb Company, 2018. [revised 2018 Apr].

2. Keytruda Prescribing Information. Whitehouse Station,NJ: Merck Sharp & Dohme Corp, 2018 [revised 2018 Jun].

3. Tecentriq Prescribing Information. San Francisco(CA): Genentech, Inc, 2018. [revised 2019 Jul].

4. Imfinzi Prescribing Information. Wilmington (DE):AstraZeneca Pharmaceuticals LP, 2018. [revised 2018 Feb].

5. Yervoy Prescribing Information. Princeton (NJ): Bristol-Myers Squibb Company, 2018. [revised 2018 Apr].

6. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ,Cowey CL, Lao CD, et al. Combined nivolumab andipilimumab or monotherapy in untreated melanoma. NEngl J Med. 2015;373:23-34.

7. Postow MA, Chesney J, Pavlick AC, Robert C, Gross-mann K, McDermott D, et al. Nivolumab and ipilimu-mab versus ipilimumab in untreated melanoma. N EnglJ Med. 2015;372:2006-2017.

8. Motzer RJ, Tannir NM, McDermott DF, FronteraOA, Melichar B, Choueiri TK, et al. Nivolumab plusipilimumab versus sunitinib in advanced renalcellcarcinoma. N Engl J Med. 2018;378:1277-1290.

9. Overman MJ, Lonardi S, Wong KYM, Lenz H-J,Gelsomino F, Aglietta M, et al. Durable clinical benefitwith nivolumab plus ipilimumab in DNA mismatchrepair–deficient/microsatellite instability–high metastaticcolorectal cancer. J Clin Oncol. 2018;36:773-779.

10. Broderick JM. Nivolumab, ipilimumab combo ap-proved by FDA for MSI-H/dMMR colorectal cancer.Pharmacy Times, 11 July, 2018. Available at: https://www.pharmacytimes.com/news/nivolumab-ipilimumab-combo-approved-by-fda-for-msihdmmr-colorectal-cancer.Accessed 18 July, 2018.

11. Antonia S, Goldberg SB, Balmanoukian A, Chaft JE,Sanborn RE, Gupta A, et al. Safety and antitumour activ-ity of durvalumab plus tremelimumab in non-small celllung cancer: a multicentre, phase 1b study. LancetOncol. 2016a;17(3):299-308.

12. Haddad R, Gillison M, Ferris RL, Harrington K,Monga M, Baudelet C, et al. Double-blind, two-arm,phase 2 study of nivolumab (nivo) in combination withipilimumab (ipi) versus nivo and ipi-placebo (PBO) as


https://www.pharmacytimes.com/news/nivolumab-ipilimumabcombo-approved-by-fda-for-msihdmmr-colorectal-cancer



first-line (1L) therapy in patients (patients) with recur-rent or metastatic squamous cell carcinoma of the headand neck (R/M SCCHN)—CheckMate 714. Ann Oncol.2016;27(suppl_6):1017TiP-TiP.

13. Kelley RK, Abou-Alfa GK, Bendell JC, Kim T-Y,Borad MJ, Yong W-P, et al. Phase I/II study of durvalu-mab and tremelimumab in patients with unresectablehepatocellular carcinoma (HCC): Phase I safety and effi-cacy analyses. J Clin Oncol. 2017;35(15_suppl):4073.

14. Janjigian YY, Ott PA, Calvo E, Kim JW, Ascierto PA,Sharma P, et al. Nivolumab ± ipilimumab in patientswith advanced (adv)/metastatic chemotherapy-refractory(CTx-R) gastric (G), esophageal (E), or gastroesophagealjunction (GEJ) cancer: CheckMate 032 study. J ClinOncol. 2017;35(15_suppl):4014.

15. Escudier B, Tannir NM, McDermott DF, FronteraOA, Melichar B, Plimack ER, et al. LBA5CheckMate214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced ormetastatic renal cell carcinoma (mRCC), includingIMDC risk and PD-L1 expression subgroups. AnnOncol. 2017;28(suppl_5):mdx440.029- mdx440.029.

P309Phase I dose-finding study of MIW815 (ADU-S100),an intratumoral STING agonist, in patients with ad-vanced solid tumors or lymphomas

Funda Meric-Bernstam, MD2, Theresa Werner3, StephenHodi4, Wells Messersmith, MD5, Nancy Lewis6, CraigTalluto7, Mirek Dostalek6, Aiyang Tao6, Sarah McWhirter8,Damian Trujillo8, Jason Luke, MD, FACP92MD Anderson Cancer Center, Houston, TX, USA;3University of Utah, Salt Lake City, UT, USA; 4Dana-Faber Cancer Institute, Boston, MA, USA; 5Universityof Colorado Cancer Center, Aurora, CO, USA; 6NovartisPharmaceuticals Corporation, East Hanover, NJ, USA;7Novartis Institutes for BioMedical Resea, Cambridge,MA, USA; 8Aduro Biotech Inc, Berkeley, CA, USA;9The University of Chicago Medicine, Chicago, IL,USACorrespondence: Funda Meric-Bernstam ([email protected])Journal for ImmunoTherapy of Cancer 2018, 6(Suppl1):P309

Janis Callister was not a contributing author and hastherefore been removed from the author list in thiscorrection article. The redundant affiliation Articu-late Science as shown on the original article is nolonger listed on this correction article.

BackgroundMIW815 (ADU-S100) is a novel synthetic cyclic di-nucleotide that can activate human STING (STimulatorof INterferon Genes) in antigenpresenting cells. In pre-clinical models, STING pathway activation can inducetumor antigen-specific T-cell priming within the tumormicroenvironment, leading to antitumor immunity andtumor destruction.

MethodsEligible patients (≥2 accessible tumors; Eastern CooperativeOncology Group Performance Status ≤1) include thosewith advanced/metastatic solid tumors or lymphomas withprogressive disease despite standard of care or for whomthere is no standard treatment.MIW815 (ADU-S100) is administered by weekly intratu-moral injections (3 weeks on/1 week off ) at escalatingdoses (starting dose: 50μg) in 28-day cycles. Primaryobjectives are to characterize safety and tolerability andto identify a recommended dose for future studies.Secondary objectives include preliminary efficacy,pharmacokinetics (PK), and pharmacodynamics (PD).The study is currently in dose escalation.

ResultsAs of June 15, 2018, 41 heavily pretreated patients(median age 62 years; range 26–80 years) with varioussolid tumors or lymphomas were enrolled. Thirty-fivepatients have discontinued from the study for the fol-lowing reasons: disease progression (n=26), physician/patient decision (n=8), and death (n=1); 6 patientscontinue to receive treatment. No dose-limiting toxic-ities (DLTs) were reported during the first cycle at anydose level. The most common (≥10% of patients)treatment-related AEs (TRAEs) were pyrexia (n=7;17.1%), injection site pain (n=6; 14.6%), and headache(n=6; 14.6%). Grade 3/4 TRAEs included increasedlipase (n=2; 4.9%) and elevated amylase, tumor pain,dyspnea, respiratory failure, and injection site reaction(n=1 each; 2.4%). Systemic MIW815 (ADU- S100) ex-posure increased with dose. On-treatment tumor bi-opsies showed increases in CD8 T cells infiltrating theinjected tumors in a subset of patients. Preliminaryantitumor activity, PK analysis, and PD data frominjected lesions, noninjection lesions, and peripheralblood, will be presented.

ConclusionsIntratumoral injection of MIW815 (ADU-S100) was welltolerated in doses tested thus far in patients withadvanced solid tumors and lymphoma, with no DLTsreported to date. Trials evaluating combinations ofMIW815 (ADU-S100) with anti-PD1 or anti-CTLA4antibodies are ongoing.


Ethics ApprovalThis study was approved by an independent ethicscommittee or institutional review board at each site.

P383Combination therapy with M7824 (MSB0011359C)and NHSmuIL12 enhances antitumor efficacy in pre-clinical cancer models

Chunxiao Xu, PhD2, Bo Marelli2, Jin Qi2, Guozhong Qin2,Huakui Yu2, Molly Jenkins2, Kin-Ming Lo2, Joern-PeterHalle2, Yan Lan, MD2

2EMD Serono Research and Development, Belmont,MA, USACorrespondence: Yan Lan ([email protected])Journal for ImmunoTherapy of Cancer 2018, 6(Suppl1):P383

Colleen Stanton was not a contributing author andhas therefore been removed from the author list inthis correction article. The redundant affiliationNucleus Global as shown on the original article is nolonger listed on this correction article.

BackgroundPD-1/PD-L1 pathway inhibition is a clinically validatedapproach in cancer therapy. However, most patients donot respond to the monotherapy due to multiple immuno-suppressive mechanisms. Combining anti-PD-1/ PD-L1with other immunotherapeutic agents targeting additionalimmunomodulatory pathways in the tumor microenviron-ment (TME) is one strategy to overcome resistance andimprove response rates. M7824 is an innovativefirst-in-class bifunctional fusion protein composed of twoextracellular domains of TGF-β receptor II (a TGF-β“trap”) fused to a human anti-PD-L1 IgG1 monoclonalantibody. Through simultaneous blockade of the PD-L1and TGF-β pathways, M7824 demonstrated enhancedanti-tumor activity in preclinical models [1]. NHS-IL12,and the surrogate NHS- muIL12, are immunocytokinesdesigned to target tumor necrotic regions to deliver IL-12into the TME, where they can activate NK cells and CD8+T cells to increase their cytotoxic functions. The surrogateNHSmuIL12 has demonstrated antitumor efficacy in pre-clinical models [2].This study is designed to investigate whether M7824treatment may further benefit from combination therapywith NHS-muIL12.

MethodsMice bearing MC38, EMT-6, or 4T1 tumors weretreated with M7824, NHS-muIL12, or combinationtherapy. Tumor growth and survival were assessed in

each model, and tumor recurrence following remis-sion and rechallenge was evaluated in the EMT-6model. Immune cell populations in the spleens andtumors were evaluated by flow cytometry and thefrequency of tumor antigen-reactive IFNγ-producingCD8+ T cells was evaluated by an ELISpot assay inthe MC38 model.

ResultsCombination of M7824 and NHS-muIL12 enhancedantitumor activity and extended the survival relativeto either monotherapy in preclinical tumor models.Combination therapy also enhanced the proliferation,infiltration, and cytotoxicity of CD8+ T cells relativeto monotherapies. In addition, the combination ther-apy increased the frequency of tumor antigenreactiveT cells and induced the generation of tumor-specificimmune memory, as demonstrated by protectionagainst tumor rechallenge.

ConclusionsThese data demonstrate that combination therapywith M7824 and NHS-muIL12 improved anti-tumorefficacy in multiple preclinical tumor models andsuggest that combining these therapies may be apromising therapeutic strategy for patients with solidtumors.

References1. Lan Y, et al. Enhanced preclinical antitumor activity ofM7824, a bifunctional fusion protein simultaneously tar-geting PD-L1 and TGF-β. Sci Trans Med. 2018;10(424).

2. Fallon J, et al. The immunocytokine NHS-IL12 as apotential cancer therapeutic. Oncotarget 2014;5(7):1869-84.

P391A phase 1b/2 trial of lenvatinib in combination withpembrolizumab in patients with advanced melanoma

Matthew Taylor, MD2, Nicholas Vogelzang, MD3, AllenCohn3, Daniel Stepan4, Robert Shumaker, PhD,4, CorinaDutcus4, Matthew Guo4, Emmett Schmidt, MD PhD5,Drew Rasco6

2Oregon Health and Science University, Portland, OR,USA; 3McKesson Specialty Health, Las Vegas, NV,USA; 4Eisai Inc., Woodcliff Lake, NJ, USA; 5Merck &Co., Inc., Kenilworth, NJ, USA; 6South Texas Acceler-ated Research Therape, San Antonio, TX, USACorrespondence: Matthew Taylor ([email protected])Journal for ImmunoTherapy of Cancer 2018, 6(Suppl1):P391


The redundant affiliation 1. Oxford PharmaGenesis,Oxford, UK as shown on the original article is nolonger listed on this correction article.

BackgroundLenvatinib is a multikinase inhibitor of VEGFR 1−3,FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab,an anti-PD-1 antibody, is approved for the first-linetreatment of patients with advanced melanoma, withobjective response rates (ORR) of 21–34% [1,2]. Pre-clinical studies indicate that lenvatinib decreases thepopulation of tumorassociated macrophages, increasesCD8+ T cell infiltration, and augments the activity ofPD-1 inhibitors; therefore, lenvatinib is a rationalcombination partner for pembrolizumab [3,4]. We re-port interim results of an ongoing phase 1b/2 trialevaluating lenvatinib in combination with pembrolizu-mab in patients with solid tumors, focusing on theadvanced melanoma cohort.

MethodsIn this multicenter, open-label study (NCT02501096),patients with measurable, confirmed, metastatic melan-oma and ECOG performance status ≤1 received lenvati-nib (20 mg/day orally) + pembrolizumab (200 mgQ3W, IV). Patients were not preselected based onPDL1 status. Tumor assessments were performed bystudy investigators using immune-related RECIST(irRECIST). The phase 2 primary end point was ORR at24 weeks (ORRWK24). Secondary end points includedORR, progression-free survival (PFS), and duration ofresponse (DOR).

ResultsAt the data cutoff of March 1, 2018, 21 patients were en-rolled: 14 (67%) patients were PD-L1(+), 4 (19%) werePD-L1(-), 3 (14%) were not tested; and 38% of patientshad ≥1 prior anticancer therapy. The primary end pointof ORRWK24 was 47.6% (95% CI, 25.7–70.2). Additionalefficacy outcomes are summarized in the table (Table 1).All patients experienced ≥1 treatment-related adverseevent (TRAE). Grade 3 and 4 TRAEs occurred in 13(62%) and 1 (5%; adrenal insufficiency) patients respect-ively. There were no fatal TRAEs. The most commonany-grade TRAEs were fatigue (52%), decreased appetite(48%), diarrhea (48%), hypertension (48%), dysphonia(43%), and nausea (43%). Dose reduction and interrup-tion due to TRAEs occurred in 13 (62%) and 10 (48%)patients, respectively.

ConclusionsThe lenvatinib and pembrolizumab combination regi-men was welltolerated and demonstrated encouragingclinical activity. The combination may potentially

improve upon the antitumor activity of antiPD-1 mono-therapies, supporting further evaluation of this regimenin patients with advanced melanoma.


References1. Ribas A, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melan-oma (KEYNOTE-002): a randomised, controlled, phase2 trial. Lancet Oncology. 2015;16(8):908-18.

2. Robert C, et al. Pembrolizumab versus ipilimumab inadvanced melanoma. N Engl J Med. 2015;372(26):2521-2532.

3. Kato Y et al. Effects of lenvatinib on tumor-associatedmacrophages enhance antitumor activity of PD-1 signalinhibitors. Mol Cancer Ther. 2015;14 (12Suppl2):A92.

4. Kato Y. Upregulation of memory T cell population andenhancement of Th1 response by lenvatinib potentiate an-titumor activity of PD-1 signaling blockade. Cancer Res.2017;77 (13 Suppl):4614. Ethics Approval This study wasapproved by all relevant institutional review boards.

Table 1 (abstract P391). See text for description.

P392A phase 1b/2 trial of lenvatinib in combination withpembrolizumab in patients with non-small cell lungcancer

Marcia Brose2, Nicholas Vogelzang, MD3, ChristopherDi Simone3, Sharad Jain, MD3, Donald Richards3, CarlosEncarnacion3, Drew Rasco4, Robert Shumaker, PhD5,Corina Dutcus5, Daniel Stepan5, Matthew Guo5, EmmettSchmidt, MD PhD6, Matthew Taylor, MD7

2Abramson Cancer Center of the University, Philadelphia,PA, USA; 3McKesson Specialty Health, Las Vegas,NV,USA; 4South Texas Accelerated Research Therape, San


Antonio, TX, USA; 5Eisai Inc., Woodcliff Lake, NJ, USA;6Merck & Co., Inc., Kenilworth, NJ, USA; 7Oregon Healthand Science University, Portland, OR, USACorrespondence: Marcia Brose ([email protected]) Journal for ImmunoTherapy of Cancer 2018,6(Suppl 1):P392


BackgroundLenvatinib is a multikinase inhibitor of VEGFR 1−3,FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab, ananti-PD-1 antibody, is approved as a monotherapy forpreviously treated patients with metastatic PD-L1–positive (tumor proportion score [TPS] ≥1%) non-smallcell lung cancer (NSCLC), with an objective response rate(ORR) of 18% [1]. We report interim results of an on-going phase 1b/2 trial evaluating lenvatinib in com-bination with pembrolizumab in patient with solidtumors, focusing on the metastatic NSCLC cohort.

MethodsIn this multicenter, open-label study (NCT02501096),patients with measurable, confirmed metastatic NSCLCand ECOG performance status ≤1 received lenvatinib(20 mg/day orally) and pembrolizumab (200 mg Q3W,IV). In the phase 2 portion, patients must have had ≤2prior lines of systemic therapy; there was no limit forphase 1b. Patients were not preselected based onPD-L1 status. Tumor assessments were performed bystudy investigators using immune-related RECIST(irRECIST). The phase 2 primary end point was ORRat 24 weeks (ORRWK24). Secondary end pointsincluded ORR, progressionfree survival (PFS), andduration of response (DOR).

ResultsAt the data cutoff of March 1, 2018, 21 patients were en-rolled. 9 (43%) Patients were PD-L1(+) (TPS ≥1%); 5(24%) were PD-L1(-); 7 (33%) were not tested. 3 (14%)Patients were treatment-naïve; 7 (33%), 10 (48%), and 1(5%) patients had 1, 2, and ≥3 prior lines of systemictherapy, respectively. The primary end point ofORRWK24 was 33.3% (95% CI, 14.6–57.0). Additionalefficacy outcomes are summarized in the table (Table 1).Grade 3 and 4 treatment-related adverse events (TRAEs)occurred in 10 (48%) and 1 (5%; increased aspartate ami-notransferase) patients, respectively. There was 1 fatalTRAE (exsanguination; deemed “possibly related” tostudy treatment). The most common grade 3 TRAEswere hypertension (24%), fatigue (14%), diarrhea (14%),proteinuria (10%), and arthralgia (10%).

ConclusionsThe combination of lenvatinib and pembrolizumab showedpromising clinical activity with a manageable safety profile inpreviously treated patients with metastatic NSCLC who werenot preselected for PD-L1 status. Further study is warranted.


ReferencesHerbst RS et al. Pembrolizumab versus docetaxel forpreviously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised con-trolled trial. Lancet. 2016;387(10027):1540-50.

Ethics ApprovalThis study was approved by all relevant institutional re-view boards.


P393A phase 1b/2 trial of lenvatinib in combination withpembrolizumab in patients with urothelial cancer

Nicholas Vogelzang, MD2, Carlos Encarnacion2, AllenCohn2, Christopher Di Simone2, Drew Rasco3, DonaldRichards2, Matthew Taylor, MD4, Corina Dutcus5, DanielStepan5, Robert Shumaker, PhD5, Matthew Guo5, EmmettSchmidt, MD PhD6, James Mier, MD7

2McKesson Specialty Health, Las Vegas, NV, USA; 3SouthTexas Accelerated Research Therape, San Antonio, TX,USA; 4Oregon Health and Science University, Portland,OR, USA; 5Eisai Inc., Woodcliff Lake, NJ, USA; 6Merck &Co., Inc., Kenilworth, NJ, USA; 7Beth Israel DeaconessMedical Center, Boston, MA, USACorrespondence: Nicholas Vogelzang ([email protected]) Journal for ImmunoTherapy ofCancer 2018, 6(Suppl 1):P393



BackgroundPembrolizumab, an anti-PD-1 antibody, is approved in thesecondline setting for patients (objective response rate[ORR] 21%) with advanced/metastatic urothelial cancerand in the first-line setting for patients who are ineligiblefor cisplatin with combined positive score ≥10 or ineligiblefor platinum-based chemotherapy, with ORR (overall ORR29%) [1–3]. However, there is still an unmet need for effect-ive therapeutic options for advanced urothelial cancer. Len-vatinib is a multikinase inhibitor of VEGFR 1-3, FGFR 1-3,PDGFRα, RET and KIT. Tyrosine kinase inhibitors, such aslenvatinib, have demonstrated activity in urothelial cancerand may reverse the immunosuppressive environment thatleads to immuno-oncology (IO) therapy failure. Here wepresent a phase 1b/2 trial to determine the safety and effi-cacy of lenvatinib in combination with pembrolizumab inpatients with advanced urothelial cancer.

MethodsIn this multicenter, open-label study (NCT02501096), pa-tients with confirmed metastatic urothelial cancer and anECOG PS of 0 or 1 received lenvatinib 20 mg orallyonce daily and 200 mg pembrolizumab intravenouslyevery 3 weeks. Patients were not preselected based onPD-L1 status. The phase 2 primary end point wasORR at week 24 (ORRwk24), as assessed by study in-vestigators using immune-related RECIST (irRECIST).Secondary end points included ORR, duration of re-sponse (DOR), and progression-free survival (PFS).

ResultsAt the time of data cutoff (March 1, 2018), 20 patientswere enrolled. 9 (45%) Patients were PD-L1(+); 5 (25%)were PD-L1(-); 6 (30%) were not tested. 4 Patients (20%)were treatment-naïve, whereas 11 (55%) and 5 (25%) pa-tients had had 1 and 2 lines of prior anticancer therapies,respectively. No patient had received prior IO therapy.The primary end point of ORRwk24 was 25% (95% CI:8.7–49.1). Additional efficacy outcomes are summarizedin the table (Table 1). 18 (90%)Patients experienced treatment-related adverse events (TRAEs).Grade 3 and 4 TRAEs occurred in 5 (25%) and 5 (25%)patients, respectively. There was 1 fatal TRAE (gastro-intestinal hemorrhage). The most common any-gradeTRAEs were proteinuria (45%), diarrhea (40%), fatigue(30%), hypertension (30%), and hypothyroidism (30%).

ConclusionsThe tyrosine kinase inhibitor (lenvatinib) and immuno-therapy (pembrolizumab) regimen demonstrated activity

in this study, which included patients receiving later-linetreatment. The combination of lenvatinib and pembroli-zumab deserves further investigation in patients withmetastatic urothelial cancer.


References1. Bellmunt J, et al. Pembrolizumab as second-line ther-apy for advanced urothelial carcinoma. N Engl J Med.2017;376(11):1015-26.2. Vuky J et al. Updated efficacy and safety ofKEYNOTE-052: A single arm phase 2 study investigatingfirst-line pembrolizumab (pembro) in cisplatin-ineligibleadvanced urothelial cancer (UC). J Clin Oncol. 2018;36(15Suppl):4524.3. Keytruda® (pembrolizumab) [package insert]. White-house Station, NJ: Merck & Co., Inc.; 2017.

Ethics ApprovalThis study was approved by all relevant institutional re-view boards.


P569Novel Pharmacobiotic approach to enhance the tam-oxifen efficacy using bacterial extracellular vesiclesas the immunotherapy in breast cancer

Jeongshin An, MD,PhD1, Yeun-yeoul Yang1, Won-HeeLee2, Jinho Yang2, Jong-kyu Kim1, HyunGoo Kim1, SeHyun Paek1, Jun Woo Lee1, Joohyun Woo1, Jong BinKim1, Hyungju Kwon1, Woosung Lim1, Nam Sun Paik1,Yoon-Keun Kim2, Byung-In Moon1

1Ewha Womans University, Seoul, Korea, Republic of;2MD healthcare company, Seoul, Korea, Republic ofCorrespondence: Jeongshin An ([email protected])Journal for ImmunoTherapy of Cancer 2018, 6(Suppl 1):P569

Byung-In Moon is a contributing author and hastherefore been added to the author list in this correc-tion article.


BackgroundThe anti-cancer effect of bacteria has a long history. Ac-cording to Bierman et al., spontaneous remission of cancerhas been observed in patients with severe bacteremia [1].The reason was not revealed at that time, but we studiedthat in breast cancer. There are four main ways in whichmicrobiota affects cancer: probiotics, prebiotics, drugs thattarget microbial enzymes and microbial products that haveanticancer properties [2]. Among them, bacterial extracellu-lar vesicles(EVs) are one of microbial products. In thisstudy, we investigated the effects of bacterial EVs on thegrowth of breast cancer cells and tamoxifen efficacy.

MethodsHere, we analized microbiota of urine samples by NGS toselect the target EVs that were expected to affect the growthof breast cancer cells. A total of 347 female urine samples –from 127 breast cancer patients (cancer group) and 220normal individuals (control group) – were collected and an-alyzed by NGS using a universal bacterial primer of 16SrDNA. Human breast cancer cells were cultured, and thecells were treated with EVs of S. aureus and K.pneumoniaefor 72 h. Real-time polymerase chain reaction (PCR) andWestern blotting for signalling molecule analysis were per-formed after treatment of EVs in each breast cancer cell.

ResultsThere was a significant difference in the distribution of bac-terial EVs between the urine samples from breast cancerpatients and from normal controls. Especially, S.aureus EVswere predominant in the normal group, and K.pneumoniaewas abundant in the breast cancer group. Therefore, weselected these two bacterial EVs that may have an effect onbreast cancer cell growth. We found that S.aureus andK.pneumoniae EVs down-regulated cell growth inMDA-MB-231 cells. We also found that S.aureus orK.pneumoniae EVs had a synergic effect on growth inhib-ition of while co-treated with tamoxifen. S.aureus EVsdown-regulated mRNA expression of cyclin E2 and up-regulated that of TNF-alpha which was related ERK path-way while co-treated with tamoxifen.

ConclusionsThe anti-cancer effect of S.aureus and K.pneumoniae wasinitiated by its bacterial EVs and consequently inhibited thegrowth of breast cancer cells in triple negative breast cancercells and improved the efficacy of tamoxifen in ER-positivecells. In the near future, we plan to conduct animal studieswhich are expected to further clarify the effect of bacterialEV on breast cancer.

Ethics ApprovalThe study was approved by Ewha Womans UniversityMedical Center‘s Ethics Board.

ConsentWritten informed consent was obtained from the patientfor publication of this abstract and any accompanyingimages. A copy of the written consent is available for re-view by the Editor of this journal.

References

1. Bierman, H. R. et al. Remissions in leukemia of child-hood following acute infectious disease. Staphylococcusand streptococcus, varicella, and feline panleukopenias.Cancer 6, 591-605 (1953).

2. Zitvogel, L., Daillère, R., Roberti, M. P., Routy, B. &Kroemer, G. Anticancer effects of the microbiome andits products. Nature Reviews Microbiology 15, 465(2017).

Fig. 1 (abstract P569). See text for description








P651

First-in-human study of FAZ053, an anti-PD-L1 mAb,alone and in combination with spartalizumab, an anti-PD-1 mAb, in patients with advanced malignancies

Filip Janku, MD, PhD2, David Tan3, Juan Martin-Liberal4,Shunji Takahashi5, Ravit Geva, MD6, Ayca Gucalp7, XueyingChen8, Kulandayan Subramanian9, Jennifer Mataraza9,Jennifer Wheler9, Philippe Bedard, MD10

2MD Anderson Cancer Center, Houston, TX, USA; 3Na-tional University Cancer Institute, Singapore, Singapore4Vall d’Hebron Institute of Oncology, Barcelona, Spain;5The Cancer Institute Hospital of JFCR, Tokyo, Japan;6Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel;7Memorial Sloan Kettering Cancer Center, New York,NY, USA 8Novartis Pharmaceuticals Corporation, EastHanover, NJ, USA 9Novartis Institutes for BioMedicalResea, Cambridge, MA, USA; 10Princess Margaret Can-cer Centre, Toronto, ON, Canada

Correspondence: Filip Janku ([email protected])Journal for ImmunoTherapy of Cancer 2018, 6(Suppl1):P651

Janis Callister was not a contributing author and hastherefore been removed from the author list in thiscorrection article. The redundant affiliation ArticulateScience as shown on the original article is no longerlisted on this correction article.

BackgroundFAZ053 and spartalizumab are humanized immuno-globulin G4 monoclonal antibodies (mAbs) that bindanti-programmed death ligand-1 (PD-L1) and pro-grammed death-1 (PD-1), respectively. We report thedose-escalation results from an ongoing Phase I studyof FAZ053 ± spartalizumab in patients with advancedmalignancies, enriched for patients with chordoma, arare subtype of sarcoma.


MethodsPatients received escalating doses of single-agent (SA)FAZ053 intravenously once every 3 weeks (Q3W) or 6weeks (Q6W), or FAZ053 + spartalizumab Q3W. Theprimary objective was to assess the safety and tolerabilityof FAZ053 ± spartalizumab, and determine recom-mended doses for expansion (RDEs). Dose escalationwas guided by an adaptive Bayesian logistic regressionmodel following the escalation with overdose controlprinciple.

ResultsAs of the data cutoff of March 30, 2018, 61 patients re-ceived SA FAZ053 at doses 80–1600 mg Q3W or 800–1600 mg Q6W. Most patients (n=54; 89%) received priortreatment; 1 (2%) received prior anti-PD-1. FAZ053 ex-posure was generally dose proportional, with terminalhalf-life of ~16–18 days. A dose-limiting toxicity oc-curred in 1 patient (Grade 4 renal failure; FAZ053 1600mg Q6W). RDE was determined to be 1200 mg Q3W or1600 mg Q4W. Adverse events (AEs) of all gradesassessed as possibly related to treatment were reportedfor 33 patients (54%); most commonly (≥10%) fatigue(n=11;18%) and pruritus (n=8; 13%); 4 patients (7%) hadGrade 3/4 treatment-related AEs, including elevatedamylase (3%), renal failure, elevated lipase, elevated AST,and elevated blood CPK (each 2%). For these patientstreated with SA FAZ053, partial responses (PRs) weredemonstrated in 4 patients (7%) with chordoma, alveolarsoft part sarcoma (ASPS), poorly differentiated carcin-oma of scalp, and penile squamous cell carcinoma (dur-ation of treatment 5.5–12.5 months; all with treatmentongoing). Among 5 patients with chordoma treated withSA FAZ053, 1 patient has a PR, treatment ongoing >12months, and 4 patients have stable disease ongoing (+4%to –29%). Data for 57 patients treated with combinationFAZ053 (20–1200 mg) + spartalizumab 300 mg Q3Ware preliminary. Updated results and biomarker data forpatients receiving SA and combination treatment,including additional patients with chordoma, will bepresented.

ConclusionsSA FAZ053 was well tolerated and the RDE was deter-mined to be 1200 mg Q3W. Clinical activity was ob-served in a range of indications including chordoma, arare tumor without standard therapy options.

Trial Registrationwww.clinicaltrials.gov; NCT02936102

Ethics approval and consent to participateThis study was approved by an independent ethics committee orinstitutional review board at each site.

Author details1Johns Hopkins University School of Medicine, Baltimore, MD, USA.2MedImmune, Gaithersburg, MD, USA. 3Peter MacCallum Cancer Center,Melbourne, Australia. 4Nucleus Network, Melbourne, Australia. 5ScientiaClinical Research, Sydney, Australia. 6Seoul National University Hospital, Seoul,Korea, Republic of. 7Yonsei Cancer Center, Yonsei University, Seoul, Korea,Republic of. 8Samsung Medical Center, Seoul, Korea, Republic of. 9AsanMedical Center, Songpa-Gu, Korea, Republic of. 10MD Anderson CancerCenter, Houston, TX, USA. 11University of Utah, Salt Lake City, UT, USA.12Dana-Faber Cancer Institute, Boston, MA, USA. 13University of ColoradoCancer Center, Aurora, CO, USA. 14Novartis Pharmaceuticals Corporation, EastHanover, NJ, USA. 15Novartis Institutes for BioMedical Resea, Cambridge, MA,USA. 16Aduro Biotech Inc, Berkeley, CA, USA. 17The University of ChicagoMedicine, Chicago, IL, USA. 18EMD Serono Research and Development,Belmont, MA, USA. 19Oregon Health and Science University, Portland, OR,USA. 20McKesson Specialty Health, Las Vegas, NV, USA. 21Eisai Inc., WoodcliffLake, NJ, USA. 22Merck & Co., Inc., Kenilworth, NJ, USA. 23South TexasAccelerated Research Therape, San Antonio, TX, USA. 24Abramson CancerCenter of the University, Philadelphia, PA, USA. 25McKesson Specialty Health,Las Vegas, NV, USA. 26South Texas Accelerated Research Therape, SanAntonio, TX, USA. 27Eisai Inc., Woodcliff Lake, NJ, USA. 28Merck & Co., Inc.,Kenilworth, NJ, USA. 29Oregon Health and Science University, Portland, OR,USA. 30McKesson Specialty Health, Las Vegas, NV, USA. 31South TexasAccelerated Research Therape, San Antonio, TX, USA. 32Oregon Health andScience University, Portland, OR, USA. 33Eisai Inc., Woodcliff Lake, NJ, USA.34Merck & Co., Inc., Kenilworth, NJ, USA. 35Beth Israel Deaconess MedicalCenter, Boston, MA, USA. 36Ewha Womans University, Seoul, Korea, Republicof. 37MD healthcare company, Seoul, Korea, Republic of. 38MD AndersonCancer Center, Houston, TX, USA. 39National University Cancer Institute,Singapore, Singapore. 40Vall d’Hebron Institute of Oncology, Barcelona, Spain.41The Cancer Institute Hospital of JFCR, Tokyo, Japan. 42Tel Aviv SouraskyMedical Center, Tel-Aviv, Israel. 43Memorial Sloan Kettering Cancer Center,New York, NY, USA. 44Novartis Pharmaceuticals Corporation, East Hanover, NJ,USA. 45Novartis Institutes for BioMedical Resea, Cambridge, MA, USA.46Princess Margaret Cancer Centre, Toronto, ON, Canada.

References1. Benhaddi, et al. 33rd Annual Meeting & Pre-Conference Programs of the

Society for Immunotherapy of Cancer (SITC 2018). J Immuno TherapyCancer. 2018;6(Suppl 1) https://doi.org/10.1186/s40425-018-0422-y.

2. Benhaddi, et al. 33rd Annual Meeting & Pre-Conference Programs of theSociety for Immunotherapy of Cancer (SITC 2018). J Immuno TherapyCancer. 2018;6(Suppl 1) https://doi.org/10.1186/s40425-018-0423-x.


http://www.clinicaltrials.gov

https://doi.org/10.1186/s40425-018-0422-y

https://doi.org/10.1186/s40425-018-0423-x

correction to: 33rd annual meeting & pre-conference ...correction open access correction to:...

Documents