SELPAC: A 3 arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel (PT) in metastatic uveal melanoma (UM)

abstracts LBA72

Pembrolizumab for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC): Efficacy and safety results from the phase II KEYNOTE-629 study

Background: The global, single-arm, phase II KEYNOTE-629 trial (NCT03284424) studied the safety and efficacy of pembrolizumab in patients with recurrent/metastatic (R/M) cSCC. Methods: Patients with R/M cSCC received pembrolizumab 200 mg Q3W for up to 35 infusions (Grob JJ et al. J Clin Oncol. 2019;37(suppl; abstr TPS9598)). The primary end point was ORR by blinded independent central review per RECIST v1.1. Secondary end points were DOR, DCR, PFS, OS, and safety. DOR, PFS, and OS were estimated using the Kaplan-Meier method. Results of an interim analysis are presented. Results: Of 105 patients, 76.2% were male, median age was 72 years, 86.7% had previously received 1 line of systemic therapy, and 74.3% had previously undergone radiation. At data cutoff (April 8, 2019), median duration of follow-up was 9.5 months (range, 0.4-16.3 months). ORR was 34.3% (95% CI, 25.3%-44.2%); 4 patients (3.8%) achieved CR (95% CI, 1.0%-9.5%), and 32 patients (30.5%) achieved PR (95% CI, 21.9%-40.2%). Median DOR was not reached (range, 2.7-13.1þ months). Of the 36 responders, 31 patients and 7 patients had a minimum follow-up of 6 months and 12 months, respectively, after achieving response; 25 (79.5%) and 1 (65.6%) were estimated to have ongoing responses at > 6 months and >12 months, respectively. DCR (CR þ PR þ stable disease 12 weeks) was 52.4% (95% CI, 42.4%-62.2%). Median PFS was 6.9 months (95% CI, 3.1-8.5 months); 12-month PFS rate was 32.4%. Median OS was not reached (95% CI, 10.7 months-not reached); 12-month OS rate of 60.3%. Treatment-related adverse events (TRAEs) occurred in 70 patients (66.7%), and 6 patients (5.7%) had grade 3-5 TRAEs; 1 patient died of treatment-related cranial nerve neuropathy. The most common TRAEs were pruritus (14.3%), asthenia (13.3%), and fatigue (12.4%). Conclusions: Pembrolizumab demonstrated a clinically meaningful ORR (34.3%), durable responses, and remarkable PFS and OS in patients with R/M cSCC, most of whom were heavily pretreated. Treatment was well tolerated, and the safety profile was generally consistent with that of other pembrolizumab monotherapy studies; no new safety signals were identified. These data support pembrolizumab for the treatment of R/M cSCC. Clinical trial identification: NCT03284424, October 26, 2017. Editorial acknowledgement: Medical writing and/or editorial assistance was provided by Holly Cappelli, PhD, and Dana Francis, PhD, 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: J.J. Grob: Honoraria (self): Roche, Novartis, BMS, MSD, Pierre Fabre, Amgen, Sunpharma, Sanofi, Merck, Pfizer; Advisory / Consultancy: Roche, Novartis, BMS, MSD, Pierre Fabre, Amgen, Sunpharma, Sanofi, Merck, Pfizer; Travel / Accommodation / Expenses: Novartis, BMS, MSD, Pierre Fabre. N. Basset-Seguin: Research grant / Funding (institution), Financial contract with St Louis Hospital for the clinical trial: MSD. O. Vornicova: Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Travel / Accommodation / Expenses: Roche. J. Schachter: Honoraria (self): BMS; Honoraria (self): Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD. N. Meyer: Advisory / Consultancy, Research grant / Funding (institution), Personal fees: MSD; Advisory / Consultancy, Research grant / Funding (institution), Personal fees: BMS; Advisory / Consultancy, Personal fees: Roche; Advisory / Consultancy, Personal fees: Novartis; Advisory / Consultancy: Incyte; Non-remunerated activity/ies, Personal fees: Sun pharma; Advisory / Consultancy, Personal fees: Pierre Fabre. F. Grange: Advisory / Consultancy: MSD. J.M. Piulats: Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Janssen. J. Bauman: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Bayer. P.(. Zhang: Full / Part-time employment: Merck & Co., Inc.. B. Gumuscu: Full / Part-time employment: MSD. R.F. Swaby: Full / Part-time employment: Merck & Co., Inc.. B.G.M. Hughes: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Boehringer. All other authors have declared no conflicts of interest.

v908 | Melanoma and other skin tumours

LBA73

SELPAC: A 3 arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel (PT) in metastatic uveal melanoma (UM)

P. Nathan1, A. Needham2, P.G. Corrie3, S. Danson4, J. Evans5, S. Ochsenreither6, S. Kumar7, A. Goodman8, J.M.G. Larkin9, I. Karydis10, N.M. Steven11, P. Lorigan12, R. Plummer13, P. Patel14, H.M. Shaw1, S. Leyvraz6, C. Rawcliffe2, E.E. Psarelli2, L. Handley2, J.J. Sacco15 1 Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK, 2 Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK, 3Department of Oncology, Cambridge University Hospitals NHS Foundation Trust - Addenbrooke’s Hospital, Cambridge, UK, 4Cancer Clinical Trials Centre, Weston Park Hospital, University of Sheffield & Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK, 5 Department of Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK, 6 Charite´ Comprehensive Cancer Center, Charite´ - Universit€ atsmedizin Berlin, Berlin, Germany, 7Department of Oncology, Velindre NHS Trust, Velindre Cancer Centre, Cardiff, UK, 8Department of Medical Oncology, Royal Devon & Exeter Foundation Trust, Exeter, UK, 9Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London, UK, 10Department of Medical Oncology, Southampton General Hospital, University Hospitals NHS Trust, Southampton, UK, 11Department of Medical Oncology, The University of Birmingham Institute for Cancer Studies, Birmingham, UK, 12Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK, 13Northern Centre for Cancer Care, The Freeman Hospital (NHS Foundation Trust), Newcastle Upon Tyne, UK, 14 Division of Cancer & Stem Cells, University of Nottingham & Nottingham University Hospitals NHS Trust-City Hospital Campus, Nottingham, UK, 15Department of Medical Oncology, Clatterbridge Cancer Center, Wirral & University of Liverpool, Liverpool, UK Background: The MAPK pathway is constitutively activated in uveal melanoma (UM), a disease for which there remains no standard of care for metastatic disease. In a randomised phase II clinical trial, selumetinib (AZD6244, ARRY-142886), a MEKi, showed superiority vs dacarbazine (DTIC). A phase III study of the combination of selumetinib (SEL) þ DTIC however failed to show superiority over DTIC alone. Pre-clinical data support synergistic cytotoxic activity for MEKi þ taxane combinations in a number of cancer cell line models and suggest that interrupting selumetinib before taxane exposure may be beneficial. Methods: Following ethical approval, 77 patients with metastatic UM who had not received previous chemotherapy were randomised to either A: SEL 75mg bd po B: SEL 75mg bd po þ PT 80mg/m2 weeks 1, 2 and 3 (q28) or C: SEL 75mg bd po interrupted for 2 days before exposure to PT 80mg/m2 weeks 1, 2, 3 (q28) at 13 UK and 1 German sites. Primary endpoint was PFS; OS, ORR and toxicity were secondary endpoints. After an amendment, arms B & C were combined and compared to arm A for PFS, OS and ORR using intention to treat analyses. Reflecting the pooled comparison, the sample size was re-adjusted to detect hazard ratio: 0.55, 80% power at 1-sided 5% significance level. Sensitivity analysis was performed to explore whether there were detectable differences in outcome between patients receiving continuous or interrupted SEL in combination with PT (arms B & C). Results: Primary analysis was triggered after 68 events. The median PFS in the combination arms B & C was 4.8 months (95% CI: 3.8 - 5.6) compared with 3.4 months (95% CI: 2.0 - 3.9) in the SEL alone arm A (hazard ratio 0.61 [90% CI 0.41 - 0.92], 1-sided pvalue ¼ 0.022). ORR was 14% and 4% in arms B & C and A respectively. Median OS in arms B & C was 9 months and was not significantly different from arm A at 10 months (hazard ratio 0.98 [90% CI 0.58 - 1.66], 1-sided p-value ¼ 0.469). SAEs and grade 3þ toxicities were similar between treatment arms. Conclusions: SelPac met its primary endpoint, demonstrating a statistically significant improvement in PFS for SEL þ PT without a significant increase in toxicity. No trend for a prolongation of OS was observed. Clinical trial identification: ISRCTN 29621851. Legal entity responsible for the study: University of Liverpool & Liverpool Cancer Trials Unit. Funding: Cancer Research UK and AstraZeneca. Disclosure: P. Nathan: Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: AstraZeneca; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: BMS; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: Merck; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: MSD; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: Immunocore; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: Pfizer; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: Ipsen; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: 4SC; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: Roche; Research grant / Funding (self), Audit: Pfizer; Leadership role, Non-remunerated activity/ies, Chair: NCRI Bladder and Renal CSG; Leadership role, Non-remunerated activity/ies, Steering Committee and Uveal Melanoma Lead: EORTC Melanoma Group; Leadership role, Non-remunerated activity/ies, IRCI UK Uveal Melanoma Lead: IRCI UK . P.G. Corrie: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker fees and Advisory Boards: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker fees and Advisory Boards: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker fees and Advisory Boards: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker fees and Advisory Boards: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Advisory Board: Incyte; Honoraria (self), Advisory / Consultancy, Consultancy : LifeArc; Honoraria (self), Advisory / Consultancy, ISDMC membership: Celgene; Shareholder / Stockholder / Stock options, Stock ownership: Genesiscare; Research grant / Funding (institution), Commercial-sponsored clinical trials: BMS; Research grant / Funding (institution), Commercial-sponsored clinical trials: MSD; Research grant / Funding (institution), Commercial-sponsored clinical trials: Celgene; Research grant / Funding (institution), Commercial-sponsored clinical trials: Array Pharmaceuticals; Research grant / Funding (institution), Commercial-sponsored clinical trials: Immunocore; Research grant / Funding (institution), Commercial-sponsored clinical trials: Novartis; Research grant / Funding (institution), Grant

Volume 30 | Supplement 5 | October 2019

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J.J. Grob1, R. Gonzalez Mendoza2, N. Basset-Seguin3, O. Vornicova4, J. Schachter5, A. Joshi6, N. Meyer7, F. Grange8, J.M. Piulats9, J. Bauman10, P. Zhang11, B. Gumuscu11, R.F. Swaby11, B.G.M. Hughes12 1 Dermatology, AIX-Marseille University, Marseille, France, 2Surgical Oncology, Centro Estatal de Cancerologiade Chihuahua, Chihuahua, Mexico, 3Dermatology, Hoˆpital Saint-Louis, Paris, France, 4Oncology, Rambam Health Care Campus, Haifa, Israel, 5 Division of Oncology, Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel, 6 Medical Oncology, Townsville Cancer Centre, Townsville, Australia, 7Medical Oncology, IUCT–Oncopole, Toulouse, France, 8Dermatology / Oncology, CHU Reims–Hoˆpital Robert Debre, Reims, France, 9Medical Oncology, Genitourinary, Melanoma and Sarcoma Unit, Hospital Duran i Reinals ICO de Hospitalet, Barcelona, Spain, 10 Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA, 11Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA, 12Oncology, Royal Brisbane and Women’s Hospital, University of Queensland, Herston, Brisbane, Australia

Annals of Oncology

Annals of Oncology

Volume 30 | Supplement 5 | October 2019

BMS; Travel / Accommodation / Expenses, Support to attend conferences: MSD; Travel / Accommodation / Expenses, Support to attend conferences : Eisai; Travel / Accommodation / Expenses, Support to attend conferences: Bayer; Travel / Accommodation / Expenses, Support to attend conferences : Roche; Travel / Accommodation / Expenses, Support to attend conferences : Celgene; Advisory / Consultancy, Chair - review panel of clinical trial centres programme: Institut National Du Cancer . S. Ochsenreither: Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Merck; Honoraria (self): Ipsen; Honoraria (self): Janssen; Honoraria (self): CureVac; Honoraria (self): Glenmark; Honoraria (self): Incyte. J.M.G. Larkin: Honoraria (self), Advisory / Consultancy, Consultancy: Achilles; Honoraria (self), Advisory / Consultancy, Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Consultancy: Boston Biomedical; Honoraria (self), Advisory / Consultancy, Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Consultancy : Eisai; Honoraria (self), Advisory / Consultancy, Consultancy: EUSA Pharma; Honoraria (self), Advisory / Consultancy, Consultancy: GSK; Honoraria (self), Advisory / Consultancy, Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Consultancy: Imugene; Honoraria (self), Advisory / Consultancy, Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Consultancy: iOnctura; Honoraria (self), Advisory / Consultancy, Consultancy: Kymab; Honoraria (self), Advisory / Consultancy, Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Consultancy: Nektar; Honoraria (self), Advisory / Consultancy, Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Consultancy: Roche/Genentech; Advisory / Consultancy, Consultancy: Secarna; Research grant / Funding (institution), Currently 3 studies estimated total for these studies: £290K: Novartis; Research grant / Funding (institution), Currently 13 studies estimated total for these studies up to £1.7M: BMS; Research grant / Funding (institution), Currently 4 studies estimated total for these studies up to present: £178: Roche; Research grant / Funding (institution), Currently 4 studies estimated total for these studies up to present: £470K: Pfizer; Research grant / Funding (institution), Currently 1 study estimated total for these studies up to present: £275K: Covance; Advisory / Consultancy, Currently 1 study estimated total for these study up to present: £30K: Immunocore; Advisory / Consultancy, Currently 1 study estimated total for these study up to present: £20K: Pharmacyclics; Research grant / Funding (institution), Currently 1 study estimated total for these study up to present: £40K: Aveo; Research grant / Funding (institution), Currently 1 study estimated total for these study up to present: £20K: Nektar Therapeutics; Research grant / Funding (institution), Currently 4 studies estimated total for these studies up to present: £200K: Merck, Sharp & Dohme Limited (MSD); Research grant / Funding (institution), Currently 1 study estimated total for these study up to present: £100K: Achilles Therapeutics. I. Karydis: Honoraria (self), Advisory / Consultancy, Consultancy, public speaking : Delcath Inc; Honoraria (self), Advisory / Consultancy, Advisory board: Merck Serono ; Honoraria (self), Advisory / Consultancy, Public speaking : Pierre Fabre Ltd. N.M. Steven: Honoraria (institution), Speaker Bureau / Expert testimony, Fee for speaking paid to employees: Merck Serono; Leadership role, Nonremunerated activity/ies, Chair melanoma subgroup NCRI skin cancer CSG. member of same CSG: NCRI. R. Plummer: Honoraria (self), Advisory / Consultancy: Pierre Faber; Honoraria (self), Advisory / Consultancy: Genmab; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Octimet; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Karus Therapeutics; Honoraria (self), Advisory / Consultancy: Biosceptre; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Honoraria for attending advisory boards: Sanofi Aventis; Honoraria (self), Speaker Bureau / Expert testimony, Honoraria for giving educational talks: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Honoraria for giving educational talks: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, Honoraria for giving educational talks: Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Honoraria for giving educational talks: Tesaro ; Honoraria (self), Speaker Bureau / Expert testimony, Honoraria for giving educational talks: BMS; Honoraria (self), Speaker Bureau / Expert testimony, Honoraria for giving educational talks: Expert Medical Events ; Licensing / Royalties, Discretionary payment from Newcastle University (royalty payments received Clovis Oncology): Newcastle University; Research grant / Funding (self), Part funding of CASE PhD studentship: AstraZeneca; Research grant / Funding (institution), Clinical trial costs from multiple trial sponsors to cover costs of clinical investigators: Sponsor’s; Non-remunerated activity/ies, Principal Investigator on multiple trials with multiple sponsors (>30 over last 2 years): Sponsor’s. P. Patel: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker & Ad hoc Advisory Board: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Ad hoc Advisory Board: Novartis; Honoraria (self), Advisory / Consultancy, Ad hoc Advisory Board: Eisai; Honoraria (self), Advisory / Consultancy, Ad hoc Advisory Board: Merck; Honoraria (self), Speaker Bureau / Expert testimony, Speaker: Pfizer; Honoraria (self), Advisory / Consultancy, Ad hoc Advisory Board: Ipsen; Research grant / Funding (institution), Research funding: Scancell; Non-remunerated activity/ies, PI for clinical trial sponsored by Scancell: Scancell; Leadership role, Non-remunerated activity/ies, Head of Division of Cancer & Stem Cells, University of Nottingham: Cancer & Stem Cells, University of Nottingham; Leadership role, Non-remunerated activity/ies, Chairman of NCRI, Skin Cancer Study Group: NCRI, Skin Cancer Study Group. H.M. Shaw: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory/consulting/speakers bureau: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory/consulting/speakers bureau: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory/consulting/speakers bureau: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory/consulting/speakers bureau: Sanofi-Genzyme; Research grant / Funding (institution), Clinical trial funding: Novartis; Research grant / Funding (institution), Clinical trial funding: Sanofi-Genzyme; Research grant / Funding (institution), Clinical trial funding: Genmab; Research grant / Funding (institution), Clinical trial funding: Roche; Research grant / Funding (institution), Joint working project - project manager funding: BMS; Research grant / Funding (institution), Joint working project - NMP funding: Novartis; Research grant / Funding (institution), Data manager funding: Immunocore; Non-remunerated activity/ies, Principal Investigator: Novartis; Non-remunerated activity/ies, Principal Investigator: Merck; Non-remunerated activity/ies, Principal Investigator: Genmab; Non-remunerated activity/ies, Principal Investigator: Roche; Non-remunerated activity/ies, National Coordinating Investigator: Idera; Non-remunerated activity/ies, National Coordinating Investigator: Iovance; Nonremunerated activity/ies, National Coordinating Investigator : MacroGenics; Non-remunerated activity/ies, Project board - BMS/Mount Vernon - Immuno Pt Pathway: Bristol-Myers Squibb; Nonremunerated activity/ies, Project lead - Novartis/Mount Vernon - Non-Medical Prescriber Clinic: Novartis. S. Leyvraz: Honoraria (self), Advisory / Consultancy, Consultancy: Bayer. C. Rawcliffe: Research grant / Funding (institution), Externally sponsored scientific research grant: AstraZeneca . J.J. Sacco: Honoraria (self), Advisory / Consultancy, Speaker/ presenter/ interview for video: BMS; Honoraria (self), Advisory / Consultancy, Advisory board: MSD; Honoraria (self), Advisory / Consultancy, Advisory board: Delcath; Honoraria (self), Advisory / Consultancy, Advisory board: Amgen; Honoraria (self), Advisory / Consultancy, Speaker : Pierre Fabre; Honoraria (self), Advisory / Consultancy, Advisory board/ consultancy: Immunocore; Research grant / Funding (institution), Trial funding (as co-CI): AstraZeneca; Research grant / Funding (institution), Trial funding (as CI): BMS; Research grant / Funding (institution), Trial funding (local PI): Immunocore; Research grant / Funding (institution), Trial funding (local PI): Replimune; Research grant / Funding (institution), Trial funding (local PI): Amgen ; Research grant / Funding (institution), Trial funding (local PI):

doi:10.1093/annonc/mdz394 | v909

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for investigator led trials: Celgene; Non-remunerated activity/ies, UK Chief Investigator for clinical trials sponsored by Halozyme: Halozyme; Non-remunerated activity/ies, UK Chief Investigator for clinical trials sponsored by Novartis: Novartis; Non-remunerated activity/ies, UK Chief Investigator for clinical trials sponsored by BMS: BMS; Leadership role, Non-remunerated activity/ies, Chair : NCRI pancreatic cancer workstream. S. Danson: Honoraria (self), Speaker Bureau / Expert testimony, Speaker bureau, lecturer: Amgen; Honoraria (self), Travel / Accommodation / Expenses, Conference attendance and travel: MSD; Honoraria (self), Travel / Accommodation / Expenses, Conference attendance and travel: BMS; Honoraria (self), Advisory / Consultancy, Consultancy: GSK; Honoraria (self), Advisory / Consultancy, Consultancy: Incanthera; Honoraria (self), Travel / Accommodation / Expenses, Conference attendance and travel: AbbVie; Honoraria (self), Advisory / Consultancy, Advisory board: MSD; Honoraria (self), Advisory / Consultancy, Advisory board: BMS; Honoraria (self), Honararium: Aquarius; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: BMS; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: MSD; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Boehringer; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Virttu; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Amgen; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Novartis; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Sierra; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Bayer; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Lilly; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: AstraZeneca; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Astex; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: Immunocore; Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: NeRRe therapeutics; Leadership role, NIHR National specialty head for cancer; early phase trials (renumerated for 4 hours per week) : NIHR ; Leadership role, Sheffield ECMC Lead - funding from CRUK and Department of Health: Sheffield Experimental Cancer Medicine Centre (ECMC); Research grant / Funding (institution), Multiple clinical trials run by the University of Sheffield: GSK. J. Evans: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker, Advisory Board: BMS; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker, Advisory Board: Eisai; Honoraria (institution), Speaker Bureau / Expert testimony, Speaker: Bayer; Honoraria (institution), Speaker Bureau / Expert testimony, Speaker: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker, Advisory Board: Celgene; Honoraria (institution), Speaker Bureau / Expert testimony, Speaker: MSD; Honoraria (institution), Advisory / Consultancy, Advisory Board: Nucana; Honoraria (institution), Advisory / Consultancy, Advisory Board: Modulate Therapeutics; Honoraria (institution), Advisory / Consultancy, Chair ISDMC: Genmab; Honoraria (institution), Advisory / Consultancy, Member TSC: BMS; Honoraria (institution), Advisory / Consultancy, Leadership role, Membership of advisory board (honorarium payments to employing institution): Karus Therapeutics; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: AstraZeneca; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Basilea; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: BMS; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Bayer; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Celgene; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: MSD; Honoraria (institution), Leadership role, Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Mina Therapeutics; Research grant / Funding (institution), Institutional financial interests all payable to institution for commercial clinical trials: Roche; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Medovia; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Pfizer; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Sierra; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Verastem; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Lilly; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Eisai; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Nucana; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: GSK; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Novartis; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Immunocore; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Bicycle therapeutics; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Halozyme; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Berg; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Johnson and Johnson; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Cytomx; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Beigene; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Vertex; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Plexxikon; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Biolinerx; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Boehringer; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Athenex; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Lion / Iovance; Research grant / Funding (institution), Institutional financial interests - all payable to institution for commercial clinical trials: Adaptimmune; Leadership role, Non-remunerated activity/ies, Clinical expert review panel, Clinical research committee, ECMC - industry alliance joint SC: Cancer Research UK; Leadership role, Non-remunerated activity/ies, NCRI Upper GI Clinical Group, member of occular and pancreas subgroup: NCRI; Leadership role, Non-remunerated activity/ies, Chair catalyst committee: Breast Cancer Now; Leadership role, Non-remunerated activity/ies, Member of the grants panel : Pancreatic Cancer Research Fund; Leadership role, Non-remunerated activity/ies, EORTC GI group member: EORTC; Honoraria (institution), Leadership role, Clinical subjects editor, honorarium payable to institution : British Journal of Cancer; Leadership role, Non-remunerated activity/ies, Chair, ISDMC: Wales Clinical Trials Unit; Leadership role, Non-remunerated activity/ies, Abstract reviewer committee: ILCA; Non-remunerated activity/ies, Member: British Association for Cancer Research; Non-remunerated activity/ies, Member : European Association for Cancer Research; Non-remunerated activity/ies, Member: Association of Cancer Physicians ; Non-remunerated activity/ies, Member: ESMO; Non-remunerated activity/ies, Member: ASCO; Non-remunerated activity/ies, Member: AACR; Travel / Accommodation / Expenses, Support to attend conferences :

abstracts

abstracts MSD; Research grant / Funding (institution), Trial funding (local PI): Delcath; Leadership role, Nonremunerated activity/ies, Member of the H&N clinical studies group: H&N clinical studies group; Travel / Accommodation / Expenses, travel and conference attendance-: BMS; Travel / Accommodation / Expenses, Travel and conference attendance-: MSD. All other authors have declared no conflicts of interest.

LBA74

Phase II study of neoadjuvant cemiplimab prior to surgery in patients with stage III/IV (M0) cutaneous squamous cell carcinoma of the head and neck (CSCC-HN)

Background: Cutaneous squamous cell carcinoma (CSCC) harbors a high tumor mutation burden (TMB) due to ultraviolet light-mediated DNA damage, and are highly immune-responsive. Cemiplimab, a monoclonal antibody directed against programmed death 1 (PD-1), is approved by the FDA and EMA as treatment for advanced CSCC patients who are not candidates for curative surgery. Here we explore the efficacy of neoadjuvant cemiplimab in CSCC- head and neck (HN) patients for whom surgery and radiation was planned. Methods: Patients with stage III/IV (M0) (AJCC 8th Ed) CSCC-HN were treated with 2 doses of cemiplimab 350 mg intravenously every 3 weeks prior to surgery. The primary endpoint was overall response rate (ORR) per RECIST v1.1. Secondary endpoints included pathologic response rate, safety and tolerability, and analysis of candidate biomarkers from pre- and post-treatment blood and tumor specimens. Results: Twenty patients (18M, 2F) enrolled with median age 69 years (range: 42-88) and stage III (n ¼ 8) or IV (n ¼ 12) disease. Seven (35%) patients experienced grade 1 or 2 adverse events (AEs); 6 (30%) grade 1 rash/pruritis, 1 (5%) grade 2 myalgia, and 1 (5%) grade 2 fatigue. There were no grade  3 AEs and no surgical delays. ORR by RECIST was 30% (6 partial response, 12 stable disease, 2 progressive disease). Pathologic complete response (pCR) was observed in 11 (55%) patients and major pathology response (MPR,  10% viable tumor) in an additional 3 (15%) patients. TMB and PD-L1 expression analyses in pre-treatment samples are in process. Eleven (55%) patients did not receive planned radiotherapy after surgery based on the pathologic responses. No recurrences have been observed with a median follow up of 3.8 months (range: 1.5-11.2). Conclusions: Neoadjuvant cemiplimab was well-tolerated and induced a pCR or MPR in 70% of stage III/IV (M0) CSCC patients. A multicenter phase II study is planned to confirm these results and to describe the ability of neoadjuvant cemiplimab to allow less extensive treatment. Clinical trial identification: NCT03565783. Legal entity responsible for the study: The University of Texas MD Anderson Cancer Center. Funding: Regeneron. Disclosure: N. Gross: Advisory / Consultancy, Research grant / Funding (self): Regeneron; Advisory / Consultancy: PDS Biotechnology; Advisory / Consultancy: Intuitive Surgical. B.S. Glisson: Research grant / Funding (institution): Pfizer; Research grant / Funding (self): ISA Pharmaceuticals. All other authors have declared no conflicts of interest.

v910 | Melanoma and other skin tumours

LBA75

18-months relapse-free survival (RFS) and biomarker analyses of OpACIN-neo: A study to identify the optimal dosing schedule of neoadjuvant (neoadj) ipilimumab (IPI) 1 nivolumab (NIVO) in stage III melanoma

E.A. Rozeman1, A.M. Menzies2, O. Krijgsman3, E.P. Hoefsmit3, B.A. van de Wiel4, K. Sikorska5, T.M. Van3, H. Eriksson6, C. Bierman4, M. Gonzalez2, K. Shannon7, A. Broeks4, R. Kerkhoven8, A.J. Spillane7, R.P. Saw7, A.C.J. van Akkooi9, R.A. Scolyer10, J. Hansson6, G.V. Long2, C.U. Blank1 1 Medical Oncology Department, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 2Department of Medical Oncology, Melanoma Institute Australia, University of Sydney, North Sydney, Australia, 3 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands, 4Department of Pathology, Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 5Department of Biometrics, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 6Department of Medical Oncology, Karolinska Institutet, Stockholm, Sweden, 7Surgical Oncology, Melanoma Institute Australia, University of Sydney, North Sydney, Australia, 8Genomics Core Facility, Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands, 9Surgical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands, 10Department of Pathology, Melanoma Institute Australia, University of Sydney, North Sydney, Australia Background: Primary analysis of the OpACIN-neo study testing 3 dosing schedules of neoadj IPIþNIVO identified 2 cycles IPI 1 mg/kg þ NIVO 3 mg/kg (IPI1þNIVO3; arm B) as most favourable, with 20% grade 3-4 irAEs and a pathologic response rate (pRR) of 77%. After a median FU of 8.3 mo none of the pts with a pathologic response versus 9/21 (43%) of the non-responders had relapsed. Here we present updated RFS and biomarker analyses. Methods: OpACIN-neo is a multicentre, randomized phase II trial in resectable stage III melanoma pts with 1 measurable lymph node metastasis (RECIST 1.1). 86 pts were randomized to arm A: 2x IPI3þNIVO1 Q3W (n ¼ 30); B: 2x IPI1þNIVO3 Q3W (n ¼ 30); or C: 2x IPI3 Q3W followed by 2x NIVO3 Q2W (n ¼ 26). Lymph node dissection was planned at wk 6. Primary endpoints were toxicity, radiologic RR and pRR; RFS and biomarker analyses were secondary endpoints. Mutational profiles, gene expression signatures (GES) and immune protein expression were examined in baseline biopsies by whole exome seq, RNA seq and digital spatial profiling (DSP) analysis. Preand post-treatment plasma samples were profiled for 92 proteins. Results: After a median FU of 17.7 mo, the median RFS was not reached in any of the arms. Estimated 18-mo RFS was 85% for all pts (95% CI 78%-93%), 90% for arm A (95% CI, 80%-100%), 82% for arm B (95% CI, 70%-98%) and 83% for arm C (95% CI, 70%-100%). Relapses were observed in 1/64 (2%) pathological responders versus 13/21 (62%) of the non-responders. High tumour mutational burden (TMB) and high interferon-y (IFN-y) signature were associated with pathologic response and favourable RFS. Cytokine and PD-1 levels in plasma increased post-treatment irrespective of response. Additional GES and DSP analysis will be presented. Conclusions: The 18-mo FU confirms that durable RFS can be achieved with 2 cycles of neoadj IPIþNIVO without any additional adjuvant therapy. Pathologic response remains the strongest marker for RFS. TMB and IFN-y signature might serve as baseline markers identifying pts benefiting from neoadj IPIþNIVO. Neoadj 2 cycles IPI1þNIVO3 should be tested in a randomized phase III study versus adjuvant therapy. Clinical trial identification: NCT02977052. Legal entity responsible for the study: Netherlands Cancer Institute. Funding: BMS. Disclosure: E.A. Rozeman: Travel / Accommodation / Expenses: NanoString; Travel / Accommodation / Expenses: MSD. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre. O. Krijgsman: Research grant / Funding (institution): BMS. T.M. Van: Travel / Accommodation / Expenses: NanoString. A.C.J. van Akkooi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: MSD-Merck; Advisory / Consultancy: Merck-Pfizer; Advisory / Consultancy: 4SC. R.A. Scolyer: Advisory / Consultancy: MSD; Advisory / Consultancy: Neracare; Advisory / Consultancy: Novartis. J. Hansson: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Mass Array; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncosec; Advisory / Consultancy: Pierre-Fabre; Advisory / Consultancy: Roche. C.U. Blank: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: GSK; Advisory / Consultancy: GenMap; Advisory / Consultancy: Pierre Fabre; Research grant / Funding (institution): NanoString. All other authors have declared no conflicts of interest.

Volume 30 | Supplement 5 | October 2019

Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.070/5578311 by guest on 26 October 2019

N. Gross1, R. Ferrarotto2, P. Nagarajan3, D. Bell3, A. El-Naggar3, J.M. Johnson4, Y. Yuan5, B.S. Glisson6, M. Wong7, D. Rosenthal8, B. Esmaeli9, M.R. Migden10, J. Wargo11, R.S. Weber1, J. Myers12 1 Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 2MD Anderson Cancer Center, The University of Texas, Houston, TX, USA, 3Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 4Neuroradiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 5Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston,TX, USA, 6Thoracic/Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA, 7Melanoma Medical Oncology Department, The University of Texas M. D. Anderson Cancer Center, Houston, USA, 8 Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 9Ophthalmic Plastic Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 10Dermatology and Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, 11Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 12Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

Annals of Oncology