Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma

abstracts

Annals of Oncology Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Nektar; Advisory / Consultancy: CureVac; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Idera; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.

1374TiP

PRIME002: Early phase II study of azacitidine and carboplatin priming for avelumab in patients with advanced melanoma who are resistant to immunotherapy

Background: Melanoma patients with disease progression on immunotherapy have very limited treatment options. Low-dose azacitidine results in demethylation and increase in neoantigen expression and carboplatin increases DNA-damage and cellular stress. This trial is testing if sequential treatment with azacitidine and carboplatin “primes” for immunotherapy rechallenge with anti-PDL1 antibody Avelumab, via a decrease in the disease burden and re-establishment of immune sensitivity. Primary Objective: Quantify complete response (CR), partial response (PR), stable disease (SD), overall response rate (ORR) and clinical benefit rate (CBR) after 2 cycles of priming (1 cycle¼ azacitidine x 5 days followed by Carboplatin Day 8/28 days) according to RECIST 1.1 and 6 cycles of immunotherapy (1 cycle¼ 1 dose of Avelumab/14 days) according to irRECIST criteria. Secondary Objectives: 1. Determine DNA methylation levels before, and immediately after priming with azacitidine and carboplatin treatment i.e. at study entry and after 2 months; 2. Quantify immune-response markers (PDL-1, PD-1, CD4/CD8, and CD68) in blood, tumour and microenvironment and immune response in blood before treatment, after 2 priming cycles and after 6 immunotherapy cycles. Trial design: Interventional early phase II study that consists of 2 cycles of azacitidine 40mg/m2 IV/day for 5 days followed by Carboplatin AUC 4.5 IV on D8/ 28 day cycle and RECIST1.1 after completion of priming; followed by Avelumab 10mg/kg IV/14 day cycle until disease progression according to irRECIST. A favourable or stable response in 20% patients and no grade 4 or persistent (>4 weeks) grade 3 treatment-related adverse events (TRAEs) is required for continuation of the trial. This early phase II study will assess the feasibility and determine outcome measures required to calculate sample sizes and develop a statistical plan for multi-centre Phase II study. This study has been approved by the Northern Sydney Local Health District HREC, reference number HREC/17/HAWKE/55’. Clinical trial identification: ACTRN12618000053224; registered 16th January 2018. Legal entity responsible for the study: Andre van der Westhuizen. Funding: Ramaciotti Foundation and Hunter Medical Research Institute, Australia. Disclosure: All authors have declared no conflicts of interest.

1375TiP

Pembrolizumab (pembro) plus lenvatinib (len) for first-line treatment of patients (pts) with advanced melanoma: Phase III LEAP-003 study

A.M.M. Eggermont1, M.S. Carlino2, A. Hauschild3, P.A. Ascierto4, A. Arance5, A. Daud6, S.J. O’Day7, M.H. Taylor8, A. Smith9, A. Rodgers10, B. Homet Moreno10, S.J. Diede10, H. Kluger11 1 Medical Oncology, Gustave Roussy Cancer Campus Grand Paris and University ParisSaclay, Villejuif, France, 2Medical Oncology, Westmead and Blacktown Hospitals, Melanoma Institute Australia, and The University of Sydney, Sydney, Australia, 3 Dermatological Oncology, University Hospital Schleswig-Holstein, Kiel, SchleswigHolstein, Germany, 4Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy, 5 Medical Oncology, Hospital Clinic de Barcelona, Barcelona, Spain, 6Medicine, University of California, San Francisco, CA, USA, 7Medical Oncology, John Wayne Cancer Institute, Santa Monica, CA, USA, 8Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA, 9Clinical Oncology, Eisai Ltd., Hatfield, UK, 10Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA, 11Medical Oncology, Yale Cancer Center, Yale New Haven Hospital, New Haven, CT, USA Background: Pembro, a PD-1 inhibitor, has shown effective antitumor activity, durable responses, and survival benefit in pts with advanced melanoma. Len—a potent inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor a, RET, and KIT— plus a PD-1 inhibitor showed superior antitumor efficacy to either agent alone in a murine tumor model. Len þ pembro showed antitumor activity and was well tolerated in pts with advanced melanoma in the phase Ib/II KEYNOTE-146 trial. LEAP-003 will compare the efficacy and safety of pembro 6 len in advanced melanoma (NCT03820986). Trial design: Eligibility criteria include 18 y, histologically/cytologically confirmed unresectable untreated stage III-IV melanoma, documented BRAFV600 status, ECOG performance status 0/1, toxicity resolution from most recent therapy, and provision of baseline tumor sample. Prior first-line standard of care targeted therapy allowed only if pt has BRAFV600-mutant disease. Prior targeted therapy or immunotherapy (as adjuvant/neoadjuvant) allowed if relapse did not occur during treatment or  6 mo after

Volume 30 | Supplement 5 | October 2019

IsaPhamaceuticals, MSD, Novartis, Pfizer, Sanofi, Sellas, SkylineDx; Advisory / Consultancy: Actelion, BMS, GSK, Ellipses, Incyte, IO Biotech, IsaPhamaceuticals, MSD, Novartis, Pfizer, Sanofi, Sellas, SkylineDx; Speaker Bureau / Expert testimony: MSD. M.S. Carlino: Honoraria (self): MSD, BMS; Advisory / Consultancy: MSD, BMS, Novartis, Roche, Merck, Pierre Fabre. A. Hauschild: Honoraria (self): Amgen, BMS, MSD/Merck, Novartis, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme; Honoraria (institution), Support for clinical trials: Amgen, BMS, MerckSerono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme; Advisory / Consultancy: Amgen, BMS, MerckSerono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, OncoSec, Sanofi-Genzyme, Sun Pharma. P.A. Ascierto: Advisory / Consultancy: BMS, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, Newlink Genetics, MedImmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC; Research grant / Funding (self): BMS, Roche-Genentech, Array; Travel / Accommodation / Expenses: MSD. A. Arance: Advisory / Consultancy: BMS, MSD, Roche, Novartis, Merck; Travel / Accommodation / Expenses: BMS, MSD, Roche, Novartis, Merck. A. Daud: Advisory / Consultancy: Merck, Pfizer, BMS, Genentech, Incyte, Novartis; Shareholder / Stockholder / Stock options: SQZ; Research grant / Funding (self): BMS, Pfizer, Incyte, Checkmate, Merck. S.J. O’Day: Advisory / Consultancy: Biothera, BMS, Merck, RadImmune, ImaginAB; Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Biothera, BMS, Merck, RadImmune, ImaginAB; Research grant / Funding (institution): Amgen, Biothera, Exicure, Genocea, Incyte, Oncothereapeutics, Ultimovacs, Viralytics. M.H. Taylor: Honoraria (self): BMS, Eisai Inc, Array Biopharma, Arqule, Blueprint Medicines, Bayer, Loxo Oncology, Novartis; Advisory / Consultancy: BMS, Eisai Inc, Array Biopharma, Arqule, Blueprint Medicines, Bayer, Loxo Oncology, Novartis; Speaker Bureau / Expert testimony: BMS, Eisai Inc. A. Smith: Full / Part-time employment: Eisai. A. Rodgers: Full / Part-time employment: Merck & Co., Inc. B. Homet Moreno: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. S.J. Diede: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. H. Kluger: Research grant / Funding (institution): Merck, BMS, Apexigen; Honoraria (self): Regeneron, Alexion, Prometheus, Corvus, Nektar, Biodesix, Roche/Genentech, Pfizer, Iovance, Immunocore, Celldex, Array BioPharma.

1376TiP

Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma

S.C.F.A. Huijberts1, L. Wang2, S. Wilgenhof3, H. Rosing4, B. Nuijen4, J.H. Beijnen4, R. Leite de Oliveira2, R. Bernards2, J.H.M. Schellens5 1 Pharmacology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKIAVL), Amsterdam, Netherlands, 2Molecular carcinogenesis, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 3 Department of Medical Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), Amsterdam, Netherlands, 4Pharmacy and Pharmacology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKIAVL), Amsterdam, Netherlands, 5Pharmaceutical sciences, Utrecht University, Amsterdam, Netherlands Background: The clinical benefit of combined treatment with BRAF- and MEK-inhibitors (BRAFi; MEKi) in BRAFV600 mutant (BRAFm) melanoma is limited due to resistance after 6-14 months, associated with emerging secondary mutations. Withholding of treatment leads to reversible hyperactivation of the MAPK pathway, causing transient growth arrest and increase in Reactive Oxygen Species (ROS) in preclinical studies. Treatment of BRAFi/MEKi resistant melanoma cells with vorinostat leads to a further increase in ROS, effectively killing BRAFi resistant cells. In vivo, switch from BRAFi to vorinostat in BRAFi resistant BRAFm melanoma resulted in a decline in tumor volume. Six patients with resistant BRAFm melanoma were treated with vorinostat 360 mg QD continuously. These patients revealed regression of mutant clones and progression of BRAFi sensitive clones. Tumor biopsies showed newly developed secondary MAPK pathway mutations, e.g. NRASQ61H and KRASG12C amplifications at start and a complete absence of these resistant mutations after two weeks of vorinostat. Based on these findings we postulate that BRAFi resistant BRAFm melanoma cells can be eliminated by a short treatment with vorinostat due to killing of tumor cells harboring a secondary mutation in the MAPK pathway. In vitro experiments confirmed this hypothesis.

doi:10.1093/annonc/mdz255 | v561

Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz255.064/5576430 by guest on 26 October 2019

A. Van Der Westhuizen1, M. Graves2, R. Levy1, A. Majid1, R. Vilain3, N. Bowden2 Medical Oncology, Calvary Mater Hospital Newcastle, Newcastle, Australia, 2School of Medicine and Public Health, University of Newcastle, Callaghan, Australia, 3Anatomical Pathology, John Hunter Hospital, Newcastle, Australia

1

discontinuation. Pts will be randomized 1:1 to pembro 200 mg every 3 weeks (Q3W) IV plus len 20 mg or placebo QD PO. Randomization will be stratified by BRAF status (mutant/WT), prior adjuvant therapy (PD-1 inhibitor, yes/no), geographic region (China, yes/no). Pembro will continue for up to 2 y; len or placebo may continue beyond 2 y in cases of clinical benefit, until progression, unacceptable toxicity, or investigator/pt decision. Response will be assessed per RECIST v1.1 Q9W until wk 54, Q12W until wk 102, and Q24W thereafter. Pts with a CR can discontinue treatment after 24 wk of pembro and 2 pembro doses after initial CR. Eligible pts can continue treatment beyond initial RECIST-defined PD. AEs will be assessed for 90 d and graded per NCI CTCAE v4.0. Survival follow-up will be Q12W. Primary end points are PFS by blinded independent central review (BICR) per modified RECIST v1.1 (max target lesions: 10; 5 per organ) and OS. Secondary end points are ORR and DOR (by BICR per modified RECIST v1.1), safety, and pt-reported health outcomes. Exploratory biomarker and PK analyses of len plus pembro are planned. Clinical trial identification: NCT03820986; release date: January 29, 2019. Editorial acknowledgement: Doyel Mitra, PhD, CMPP, and Harleigh E. Willmott, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA). Legal entity responsible for the study: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure: A.M.M. Eggermont: Honoraria (self): Actelion, BMS, GSK, Ellipses, Incyte, IO Biotech,

abstracts

taxenes: Modra Pharmaceutical. All other authors have declared no conflicts of interest.

1377TiP

A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumour activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRASmutation (Ib)

L. Si1, L. Mao1, L. Zhou1, C. Li1, X. Wang1, C. Cui1, X. Sheng1, Z. Chi1, B. Lian1, B. Tang1, X. Yan1, S. Li1, X. Bai1, J. Dai1, Y. Kong1, L. Lin2, J. Zhang2, Z. Wu2, A. Hui2, J. Guo1 1 Department of Renal Cancer and Melanoma, Peking University Cancer HospitalBeijing Cancer Hospital, Beijing, China, 2Medical department, Shanghai Fosun Pharmaceutical Development Co, Ltd., Shanghai, China Background: Gain of function mutations in NRAS occurs in 15-25% of patients with melanoma, leading to activation of Ras/Raf/MEK/ERK signaling pathway results in unconstrained cell growth and cell transformation. The MEK inhibitor targets this signaling pathway, inhibiting cell proliferation and inducing apoptosis. NRAS mutation status was identified as an independent poor prognostic factor in stage IV melanoma. It is also reported that the survival of patients with high copy number (>4) was significantly worse than that of NRAS patients with 2-4 copy number (P ¼ 0.002). No drug was approved to treat melanoma patients with NRAS mutation or amplification until now. FCN-159, an oral and potent MEK1/2 inhibitor, has more than 10 folds higher selectivity against activated MEK1 and MEK2 compared with trametinib, and has demonstrated significant antitumor growth inhibition in two patient-derived xenograft (PDX) models with NRAS mutation. This is the first in human study to evaluate the safety and anti-tumor activity of FCN-159 in patients. Trial design: This is a phase Ia/Ib, open label, dose-escalation study with expansion cohort that will evaluate the safety, pharmacokinetics (PK), and preliminary antitumor activity of FCN-159 in up to 37 patients with locally advanced or metastatic melanoma harboring NRAS-aberrant including both NRAS amplification and mutation (Ia) and NRAS-mutation only (Ib). In this study, the dose escalation utilizes 3 þ 3, accelerated titration design with starting dose of 0.2 mg, QD, orally; the dose will be escalated until Maximum-Tolerated Dose (MTD) or the Recommended phase II dose (RP2D) being identified. The dose level will be considered to expand up to 6 patients if an objective response is observed, intending to collect more clinical data to support the RP2D determination. Once the MTD or RP2D is identified, an expansion cohort will be followed to further evaluate the safety and efficacy of FCN-159 in patients with NRAS-mutant melanoma. As of April 22, 2019, one patient has been dosed. Legal entity responsible for the study: Shanghai Fosun Pharmaceutical Development Co, Ltd. Funding: Shanghai Fosun Pharmaceutical Development Co, Ltd. Disclosure: All authors have declared no conflicts of interest.

1378TiP

A phase I clinical trial investigating the therapeutic cancer vaccine UV1 in combination with pembrolizumab as first-line treatment of patients with malignant melanoma

S.S. Agarwala1, S.J. O’Day2, Y. Zakharia3, B. Voorhies4, M. Milhem3 Medical Oncology, St. Luke’s Hospital & Health Network, Bethlehem, PA, USA, 2Medical Oncology, John Wayne Cancer Institute, Santa Monica, CA, USA, 3Medical Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA, 4Huntsman Cancer Institute, University of Utah, Utah, UT, USA

1

Background: This ongoing trial is investigating the safety and efficacy of combining the therapeutic cancer vaccine UV1 with the anti-PD-1 mAb pembrolizumab. UV1 is a peptide-based vaccine directed against telomerase, an essential enzyme for unlimited cell-division and a hallmark of cancer. Due to its selective expression, telomerase serves as a unique cancer antigen. UV1 consists of 3 long peptides (15-30 aa) representing fragments of the reverse transcriptase subunit of telomerase (hTERT). The peptides contain both CD4 and CD8 epitopes and are shown to be immunogenic in 78% of HLA unselected patients across different cancer types. UV1 induces hTERT-specific tumorreactive T cells, and has the potential to induce epitope spreading. UV1 can increase the

v562 | Melanoma and other skin tumours

efficacy of checkpoint inhibitors in patients with insufficient numbers of T cells spontaneously primed by tumor antigens. Reciprocally, the efficacy of UV1 may be enhanced by checkpoint inhibitors, since the effector activity of UV1-induced T cells will be restricted by intrinsic and tumor-induced suppressor mechanisms. UV1 and pembrolizumab thus have the potential to produce synergistic immunological activity which may provide increased clinical benefit as compared to pembrolizumab alone. Trial design: The ongoing phase I, open-label, multicenter study is planned to include 20 patients with untreated unresectable or metastatic melanoma. UV1 (300 lg) with GM-CSF (37,5 lg) as adjuvant is administered intradermally for a total of 8 doses, 3 doses during week 1, and one dose during week 2, 3, 8, 11 and 14. Pembrolizumab is administered every third week starting week 2 for up to two years or until progressive disease. Patients are followed for up to 2 years after the first UV1 dose. The primary objective of the study is to evaluate the safety and tolerability of the UV1 and pembrolizumab therapy. Secondary objectives are UV1 vaccine-specific immune responses and evaluation of tumor response (RECIST). Samples of blood, feces, and tumor tissue are collected for translational research purposes. Clinical trial identification: NCT03538314. Legal entity responsible for the study: Ultimovacs AS. Funding: Ultimovacs AS. Disclosure: Y. Zakharia: Advisory / Consultancy: Amegen; Advisory / Consultancy: Roche Diagnostics; Advisory / Consultancy: Novartis; Advisory / Consultancy: JNJ; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Castle Bioscience; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Bayer; Advisory / Consultancy: Array. All other authors have declared no conflicts of interest.

1379TiP

A phase II, open-label, randomized, multicenter trial of encorafenib 1 binimetinib evaluating a standard-dose and a high-dose regimen in patients with BRAFV600-mutant melanoma brain metastasis (MBM) (POLARIS)

M.A. Davies1, J.S. Weber2, K.T. Flaherty3, G.A. McArthur4, M.B. Reddy5, A. Golden6, J.L. Culbertson7, C.T. Thomas7, H.A. Tawbi1, G.V. Long8 1 Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA, 3Department of Medicine, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA, 4Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia, 5Clinical Pharmacology, Array BioPharma Inc., Boulder, CO, USA, 6Biostatistics & Data Management, Array BioPharma Inc., Boulder, CO, USA, 7Clinical Development, Array BioPharma Inc., Boulder, CO, USA, 8 Medical Oncology, Melanoma Institute Australia, University of Sydney, North Sydney, Australia Background: Melanoma that metastasizes to the brain has a poor prognosis, and accounts for up to 54% of melanoma deaths. Clinical data show that treatment with BRAF-targeted agents induces responses in RAFV600-mutant MBM. Duration of response in the brain is shorter than that observed with extracranial disease. The BRAF/MEK-targeted combination encorafenib þ binimetinib demonstrated favorable efficacy and safety for patients with BRAFV600mutant melanoma in the COLUMBUS study, but excluded patients with active MBM. The aim of this study is to evaluate encorafenib þ binimetinib in a population of patients with BRAFV600-mutated active MBM. A higher dose of combination therapy will be studied versus a standard dose to evaluate whether greater efficacy may be achieved with acceptable safety for patients with BRAFV600 MBM. Trial design: This multicenter, randomized, open-label phase II study will evaluate two dosing regimens of encorafenib þ binimetinib combination in adults with BRAFV600mutant MBM. Eligible patients will have at least 1 measurable MBM, no prior local MBM therapy, no corticosteroids for MBM, and no prior BRAF or MEK inhibitors in the metastatic setting. One prior line of checkpoint inhibitor or prior adjuvant BRAF or MEK inhibitors is permitted. Patients will be randomized (1:1) to either the standard dose (450 mg orally QD and binimetinib 45 mg orally BID) or high-dose (encorafenib 300 mg BID and binimetinib 45 mg BID) stratified by baseline tumor burden (1 to 2 brain lesions vs.  3 brain lesions at baseline) and by prior checkpoint inhibitor (yes vs. no). The first 9 evaluable patients in the high-dose arm will constitute the safety lead-in cohort. If the high-dose is not tolerated, subsequent patients will receive standard-dose therapy. Assessments include intracranial response (assessed as per modified RECIST using gadolinium enhanced MRI), extracranial response, global response rate, DCR, DOR, PFS, OS, PK, and safety. The study will enroll approximately 100 patients. Clinical trial identification: NCT03911869 Editorial acknowledgement: JD Cox and Mayville Medical Communications, with funding from Array Biopharma. Legal entity responsible for the study: Array BioPharma Inc. Funding: Array BioPharma Inc. Disclosure: M.A. Davies: Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Syndax; Non-remunerated activity/ies: Nanostring. J.S. Weber: Advisory / Consultancy, Research grant / Funding (institution): Array BioPharma; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech. K.T. Flaherty: Officer / Board of Directors: Clovis Oncology; Officer / Board of Directors: Strata Oncology; Officer / Board of Directors: Vivid Biosciences; Officer / Board of Directors: Checkmate Pharmaceuticals; Advisory / Consultancy: X4;

Volume 30 | Supplement 5 | October 2019

Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz255.064/5576430 by guest on 26 October 2019

Trial design: This is a proof of concept study to determine the efficacy of sequential treatment with vorinostat and BRAFi/MEKi in BRAFi resistant BRAFm melanoma. Patients with age  18 years, WHO performance 0-2 and progression on BRAFi/MEKi are eligible. 26 evaluable patients with resistant BRAFm melanoma will be treated with vorinostat 360 mg continuously for 2 weeks and thereafter switch back to BRAFi/ MEKi. The primary aim is to demonstrate  30% anti-tumor response of progressive lesions according to RECIST 1.1 upon sequenced treatment with vorinostat and BRAFi/MEKi. Secondary endpoints are to demonstrate that emerging resistant clones with a secondary mutation in the MAPK pathway can be detected by ctDNA analysis and purged by short term treatment with vorinostat. Blood and tumor biopsies will be taken for pharmacokinetic, pharmacodynamic and pharmacogenetic exploratory analyses. Clinical trial identification: NCT02836548. Legal entity responsible for the study: The Netherlands Cancer Institute. Funding: Oncode. Disclosure: J.H.M. Schellens: Shareholder / Stockholder / Stock options, and patent holder on oral

Annals of Oncology