- Email: [email protected]
Talimogene laherparepvec (T-VEC) in combination (combo) with ipilimumab (ipi) versus ipi alone for advanced melanoma: 3-year landmark analysis of a randomized, open-label, phase II trial
abstracts LBA69
Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (wt) advanced melanoma: Primary analysis from the phase III IMspire170 trial
Background: Treatment for pts with advanced BRAFV600 wt melanoma includes immune checkpoint inhibitors, such as P, an anti–PD-1 antibody. MAPK activation is implicated in BRAFV600 wt melanoma, and emerging data suggest that MAPK inhibition may enhance antitumor immune response to checkpoint inhibitors. In a phase I study, the combination of C, a MEK inhibitor, plus A, an anti–PD-L1 antibody, showed promising antitumor activity. In a phase III randomized study we evaluated whether CþA would improve efficacy compared with P monotherapy in pts with BRAFV600 wt advanced melanoma. Methods: Pts had previously untreated unresectable stage III or IV BRAF V600 wt melanoma. Pts were stratified by PD-L1 expression, LDH level, and geographic location, and were randomized 1:1 to receive C (60 mg, days 1-21) plus A (840 mg, every 2 wk) in 28-day cycles or P (200 mg, every 3 wk) until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. Primary endpoint was PFS, assessed by independent review committee (IRC). Key secondary endpoints were confirmed objective response rate (ORR), disease control rate (DCR), OS, and safety. Results: 446 pts were randomized to CþA (n ¼ 222) or P (n ¼ 224); 68% of pts had PD-L1–positive tumors and 25% had LDH >ULN. Median follow-up was 7 mo (range 0-15). CþA did not significantly improve IRC-assessed PFS vs P (median 5.5 vs 5.7 mo; HR 1.15; 95% CI 0.88-1.50; P ¼ 0.295). Results were consistent across pt subgroups. Confirmed IRC-assessed ORR was 26% vs 32% with CþA vs P; DCR was 46% vs 44%. Median OS was not reached in either arm (HR 1.06; 95% CI 0.69-1.61). AEs were consistent with known safety profiles of the individual agents. Grade 3 AEs occurred in 67% vs 33% of pts receiving CþA vs P; AEs leading to discontinuation of all treatments occurred in 12% vs 6%. Conclusions: IMspire170 did not meet its primary endpoint. The combination of CþA did not demonstrate an improvement in PFS vs P monotherapy in pts with BRAFV600 wt advanced melanoma. The safety profile of CþA was consistent with that observed in previous studies of this combination. Clinical trial identification: NCT03273153. Editorial acknowledgement: ApotheCom, Yardley, PA, USA. Legal entity responsible for the study: Roche. Funding: Roche. Disclosure: A.M. Arance: Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp and Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck. H. Gogas: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (institution), Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Roche. B. Dreno: Advisory / Consultancy: Roche. K.T. Flaherty: Advisory / Consultancy, Shareholder / Stockholder / Stock options, BMS: advisory/consultancy: X4 Pharmaceuticals; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Merck: advisory/consultancy; research grant (institution): PIC Therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Takeda: advisory/consultancy: Sanofi; Advisory / Consultancy, Verastem: advisory/consultancy: Amgen; Advisory / Consultancy, Boston Biomedical: advisory/consultancy: Asana; Advisory / Consultancy, Pierre Fabre: advisory/consultancy: Adaptimmune; Advisory / Consultancy, Cell Medica: advisory/consultancy: Fount; Advisory / Consultancy, Debiopharm: advisory/consultancy; research grant (institution): Aeglea; Advisory / Consultancy, Research grant / Funding (institution), Clovis Oncology: shareholder/stock: Array BioPharma; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Strata Oncology: shareholder/stock: Shattuck Labs; Advisory / Consultancy, Vivid Biosciences: shareholder/stock: Tolero; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Checkmate Pharmaceuticals: shareholder/stock: Apricity; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Oncoceutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Fog Pharma; Advisory / Consultancy: Neon; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tvardi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: xCures; Advisory / Consultancy: Monopteros; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Genentech. L. Demidov:
v906 | Melanoma and other skin tumours
Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BIOCAD; Research grant / Funding (self): Amgen. D. Stroyakovskiy: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis. Z. Eroglu: Advisory / Consultancy: Array; Advisory / Consultancy: Regeneron; Research grant / Funding (institution): Novartis. P.F. Ferrucci: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis. J. Pigozzo: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD. P. Rutkowski: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Travel / Accommodation / Expenses: Orphan Drugs. J. Mackiewicz: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. I. Rooney: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. A. Voulgari: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. S. Troutman: Full / Part-time employment: Genentech. B. Pitcher: Full / Part-time employment: Roche. Y. Yan: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Genentech. J.M.G. Larkin: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Vitaccess: honoraria (self)/advisory/consultancy/travel: Achilles; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Covance: research grant (institution): AZ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Immunocore: research grant (institution): Boston Biomedical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Pharmacyclics: research grant (institution): BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Aveo: research grant (institution): Eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EUSA Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: GSK; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Imugene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: iOnctura; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Kymab; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Secarna.
LBA70
Talimogene laherparepvec (T-VEC) in combination (combo) with ipilimumab (ipi) versus ipi alone for advanced melanoma: 3-year landmark analysis of a randomized, open-label, phase II trial
J.A. Chesney1, I. Puzanov2, F. Collichio3, P. Singh4, M. Milhem5, J. Glaspy6, O. Hamid7, M.I. Ross8, P. Friedlander9, C. Garbe10, T. Logan11, A. Hauschild12, C. Lebbe13, M. Yi14, A. Sharma15, J.M. Mehnert16 1 James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA, 2 Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA, 3Clinical Research, The University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 4Medical Oncology, Mayo Clinic, Phoenix, AZ, USA, 5Medical Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA, 6School of Medicine, University of California Los Angeles, Los Angeles, CA, USA, 7Translational Research and Immunotherapy, The Angeles Clinic and Research Institute, Santa Monica, CA, USA, 8Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 9Icahn School of Medicine, Mount Sinai, New York, NY, USA, 10Division of Dermato-Oncology, Universitaets-Hautklinik Tuebingen, Tuebingen, Germany, 11School of Medicine, Indiana University, Indianapolis, IN, USA, 12Dermatology, UK-SH, Campus Kiel, Kiel, SchleswigHolstein, Germany, 13AP-HP Dermatology Cic Departments, Hoˆpital Saint Louis, Paris, France, 14Biostatistics, Amgen Inc., Thousand Oaks, CA, USA, 15Clinical Development, Amgen Inc., Thousand Oaks, CA, USA, 16Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA Background: This is the first and only randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor in advanced melanoma. Previously, the study met its primary endpoint: the combo of T-VEC plus ipi resulted in a significantly higher objective response rate (ORR) vs. ipi alone (39% vs. 18%; odds ratio, 2.9; 95% Cl, 1.5–5.5; P ¼ 0.002) (Chesney et al. J Clin Oncol. 2017). Here, we present results from the 3-year landmark analysis. Methods: Pts with unresectable, stages IIIB to IV melanoma were randomized 1:1 to receive the combo or ipi alone. T-VEC was injected intratumorally on day 1 of wk 1 at 106 plaque-forming units (PFU)/mL followed by subsequent doses at 108 PFU/mL on day 1 of wk 4, and every 2 wks thereafter. Intravenous ipi (3 mg/kg) was given every 3 wks starting on day 1 of wk 6 for up to 4 doses. Response was assessed by investigators per immune-related response criteria every 12 wks until disease progression. The primary endpoint was ORR; key secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. This analysis occurred 36 months (mos) after the last pt was randomized.
Volume 30 | Supplement 5 | October 2019
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A.M. Arance1, H. Gogas2, B. Dreno3, K.T. Flaherty4, L. Demidov5, D. Stroyakovskiy6, Z. Eroglu7, P.F. Ferrucci8, J. Pigozzo9, P. Rutkowski10, J. Mackiewicz11, I. Rooney12, A. Voulgari13, S. Troutman12, B. Pitcher14, Y. Yan15, J.M.G. Larkin16 1 Medical Oncology, Hospital Clınic Barcelona, Barcelona, Spain, 2School of Medicine, University of Athens, Athens, Greece, 3Department of Dermatology, CHU Nantes, Nantes, France, 4Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, 5Melanoma Unit, Department of General Surgery, Russian Oncological Research Centers, Moscow, Russian Federation, 6Chemotherapy, Moscow City Oncology Hospital N 62, Moscow, Krasnogorski District, Russian Federation, 7Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA, 8Unit of Oncology of Melanoma, European Institute of Oncology, Milan, Italy, 9 Department of Cutaneous Oncology, Melanoma Oncology Unit, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy, 10Department of Soft Tissue/Bone Sarcoma, The Maria Sklodowska Curie Memorial Cancer Centre and Institute of Oncology (MCMCC), Warsaw, Poland, 11Oddział Onkologii Klinicznej i Doswiadczalnej, Uniwersytet Medyczny w Poznaniu, Pozna n, Poland, 12Product Development, Oncology, Genentech, Inc., South San Francisco, CA, USA, 13Global Product Development Clinical Science, Roche Products Ltd, Welwyn Garden City, UK, 14Product Development, Oncology, Hoffmann-La Roche Ltd., Mississauga, AB, Canada, 15Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA, 16Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London, UK
Annals of Oncology
abstracts
Annals of Oncology
Disclosure: J.A. Chesney: Advisory / Consultancy, Travel / Accommodation / Expenses: Replimune; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Licensing / Royalties, Patents, Royalties, and Other Intellectual Property: University of Louisville. I. Puzanov: Advisory / Consultancy: 4SC; Advisory / Consultancy: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck. P. Singh: Advisory / Consultancy: AstraZeneca. M. Milhem: Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Amgen; Advisory / Consultancy: Trieza; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Biontech. O. Hamid: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi/Regeneron; Research grant / Funding (institution): Arcus; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): CytomX; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): Parker; Research grant / Funding (institution), Additional research funding for institution: Polynoma. : Pfizer. M.I. Ross: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Provectus; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Castle Biosciences. P. Friedlander: Advisory / Consultancy: Regeneron; Advisory / Consultancy: Puma Biosciences; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Aspyrian Therapeutics; Shareholder / Stockholder / Stock options: Incyte; Shareholder / Stockholder / Stock options: Clovis; Shareholder / Stockholder / Stock options: Merrimack Phamaceuticals; Shareholder / Stockholder / Stock options: Allergan. C. Garbe: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Neracare; Honoraria (self), Advisory / Consultancy: Philogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi. T. Logan: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Acceleron; Research grant / Funding (institution): Abbott; Research grant / Funding (institution): Abraxis; Research grant / Funding (institution): Argos; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Aveo; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Immatics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Synta; Research grant / Funding (institution): Threshold; Research grant / Funding (institution): Millenium; Honoraria (self), Research grant / Funding (institution), Additional research funding to institution disclosure: Tracon, Cerulean, EMD Serono, Macrogenic, Peloton, Iovance, MedImmune, Dynavax. : Prometheus. A. Hauschild: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD/Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Provectus; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Philogen; Advisory / Consultancy, Research grant / Funding (institution): Regeneron; Advisory / Consultancy: OncoSec. C. Lebbe: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self): Pierre-Fabre; Honoraria (self): Pfizer; Honoraria (self): Incyte; Officer / Board of Directors: Aventis. M. Yi: Shareholder /
Volume 30 | Supplement 5 | October 2019
Stockholder / Stock options, Full / Part-time employment: Amgen. A. Sharma: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. J.M. Mehnert: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EMD Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Polynoma; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Incyte. All other authors have declared no conflicts of interest.
LBA71
Phase II multicenter open label study of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study)
H. Jespersen1, R. Olofsson Bagge2, G. Ullenhag3, A. Carneiro4, H. Helgadottir5, I. Ljuslinder6, M. Levin1, C. All-Eriksson7, B. Andersson8, U. Stierner1, L.M. Nilsson9, J.A. Nilsson9, L. Ny1 1 Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden, 2 Sahlgrenska Academy, University of Gothenburg - The Sahlgrenska Academy, Go¨teborg, Sweden, 3Oncology, University Hospital Uppsala Akademiska Sjukhuset, Uppsala, Sweden, 4Oncology and Radiation Physics, Skane University Hospital, Lund, Sweden, 5Department of Oncology, Karolinska University Hospital, Stockholm, Sweden, 6 Department of Oncology, Norrlands University Hospital, Umea˚, Sweden, 7Department of Oncology, St. Erik Eye Hospital, Stockholm, Sweden, 8Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden, 9Surgery, University of Gothenburg - The Sahlgrenska Academy, Go¨teborg, Sweden Background: While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in patients with metastatic uveal melanoma. Reports of treatment with immune checkpoint inhibitors in monotherapy have been disappointing. There is preclinical evidence that the effect of immunotherapy may be augmented by epigenetic therapy through mechanisms including enhanced expression of HLA class I and cancer antigens, and suppression of myeloid suppressor cells. Methods: We performed a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD-1 inhibitor pembrolizumab and the HDAC inhibitor entinostat in 29 adult patients with metastatic uveal melanoma. Eligible patients had histologically confirmed metastatic uveal melanoma, ECOG performance status 0–1, and measurable disease as per RECIST 1.1. Patients received pembrolizumab 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Primary endpoint was objective response rate (ORR). Secondary endpoints include clinical benefit rate (CBR; CR, PR or SD) at 18 weeks, overall survival (OS), and safety assessed by adverse events (AE). Results: At the data cut off of June 21, 2019, 29 patients had been enrolled and received at least one dose of treatment with a median follow up of 7.7 months. Ninety per cent had liver metastases and 59% had received previous treatment for metastatic disease. A partial response (PR) was observed in 3 patients resulting in an ORR of 10%. Nine patients (31%) had a best overall response of stable disease (SD). Clinical benefit at week 18 was observed in 7 out of 29 patients (24%). Median OS was 11.5 months. Twenty-eight patients (97%) experienced treatment related AEs, and grade 3-4 AEs were reported in 18 patients (62%). There were no treatment related deaths. Conclusions: The PEMDAC study has demonstrated that combined HDAC- and PD1-inhibition can result in clinical efficacy in metastatic uveal melanoma with manageable toxicities. The obtained data warrant further investigation to address clinical and immunological characteristics of patients achieving clinical benefit. Clinical trial identification: NCT02697630 (Registered 3 March 2016). EudraCT: 2016-002114-50. Legal entity responsible for the study: Sahlgrenska University Hospital, V€astra Go¨taland Region. Funding: Syndax Pharmaceuticals and Merck & Co. Inc. Disclosure: R. Olofsson Bagge: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). G. Ullenhag: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). I. Ljuslinder: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). M. Levin: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). U. Stierner: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). L. Ny: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). All other authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz394 | v907
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Results: 198 pts were randomized (98 to combo; 100 to ipi). As of 25 Feb 2019, the median follow-up time was 40.0 mos in the combo arm and 34.3 mos in the ipi arm. ORR was significantly higher with the combo vs. ipi alone (36.7% vs. 16.0%; odds ratio, 3.0; 95% CI, 1.6 to 6.0; P ¼ 0.002). Median PFS was 13.5 mos with combo and 4.5 mos with ipi (hazard ratio, 0.78; 95% Cl, 0.55–1.11; P ¼ 0.159). Median OS was not reached in either arm (HR, 0.85; 95% CI, 0.55–1.32; P ¼ 0.480). 45 pts (45.9%) in the combo arm and 64 pts (64%) in the ipi arm received subsequent anticancer therapy, with the median time from randomization to the first subsequent therapy being 27.7 mos and 8.3 mos, respectively. No new safety signals were detected. Conclusions: At the 3-year follow-up, T-VEC plus ipi combo continued to provide durable and statistically superior ORR compared with ipi alone. PFS was numerically longer with the combo than ipi. Survival is likely confounded by subsequent anticancer therapies (NCT01740297). Clinical trial identification: NCT01740297, release date December 4, 2012. Editorial acknowledgement: Medical writing assistance was provided by Yang Li (Amgen Inc). Legal entity responsible for the study: Amgen. Funding: Amgen.
Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (wt) advanced melanoma: Primary analysis from the phase III IMspire170 trial
Background: Treatment for pts with advanced BRAFV600 wt melanoma includes immune checkpoint inhibitors, such as P, an anti–PD-1 antibody. MAPK activation is implicated in BRAFV600 wt melanoma, and emerging data suggest that MAPK inhibition may enhance antitumor immune response to checkpoint inhibitors. In a phase I study, the combination of C, a MEK inhibitor, plus A, an anti–PD-L1 antibody, showed promising antitumor activity. In a phase III randomized study we evaluated whether CþA would improve efficacy compared with P monotherapy in pts with BRAFV600 wt advanced melanoma. Methods: Pts had previously untreated unresectable stage III or IV BRAF V600 wt melanoma. Pts were stratified by PD-L1 expression, LDH level, and geographic location, and were randomized 1:1 to receive C (60 mg, days 1-21) plus A (840 mg, every 2 wk) in 28-day cycles or P (200 mg, every 3 wk) until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. Primary endpoint was PFS, assessed by independent review committee (IRC). Key secondary endpoints were confirmed objective response rate (ORR), disease control rate (DCR), OS, and safety. Results: 446 pts were randomized to CþA (n ¼ 222) or P (n ¼ 224); 68% of pts had PD-L1–positive tumors and 25% had LDH >ULN. Median follow-up was 7 mo (range 0-15). CþA did not significantly improve IRC-assessed PFS vs P (median 5.5 vs 5.7 mo; HR 1.15; 95% CI 0.88-1.50; P ¼ 0.295). Results were consistent across pt subgroups. Confirmed IRC-assessed ORR was 26% vs 32% with CþA vs P; DCR was 46% vs 44%. Median OS was not reached in either arm (HR 1.06; 95% CI 0.69-1.61). AEs were consistent with known safety profiles of the individual agents. Grade 3 AEs occurred in 67% vs 33% of pts receiving CþA vs P; AEs leading to discontinuation of all treatments occurred in 12% vs 6%. Conclusions: IMspire170 did not meet its primary endpoint. The combination of CþA did not demonstrate an improvement in PFS vs P monotherapy in pts with BRAFV600 wt advanced melanoma. The safety profile of CþA was consistent with that observed in previous studies of this combination. Clinical trial identification: NCT03273153. Editorial acknowledgement: ApotheCom, Yardley, PA, USA. Legal entity responsible for the study: Roche. Funding: Roche. Disclosure: A.M. Arance: Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp and Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck. H. Gogas: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (institution), Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Roche. B. Dreno: Advisory / Consultancy: Roche. K.T. Flaherty: Advisory / Consultancy, Shareholder / Stockholder / Stock options, BMS: advisory/consultancy: X4 Pharmaceuticals; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Merck: advisory/consultancy; research grant (institution): PIC Therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Takeda: advisory/consultancy: Sanofi; Advisory / Consultancy, Verastem: advisory/consultancy: Amgen; Advisory / Consultancy, Boston Biomedical: advisory/consultancy: Asana; Advisory / Consultancy, Pierre Fabre: advisory/consultancy: Adaptimmune; Advisory / Consultancy, Cell Medica: advisory/consultancy: Fount; Advisory / Consultancy, Debiopharm: advisory/consultancy; research grant (institution): Aeglea; Advisory / Consultancy, Research grant / Funding (institution), Clovis Oncology: shareholder/stock: Array BioPharma; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Strata Oncology: shareholder/stock: Shattuck Labs; Advisory / Consultancy, Vivid Biosciences: shareholder/stock: Tolero; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Checkmate Pharmaceuticals: shareholder/stock: Apricity; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Oncoceutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Fog Pharma; Advisory / Consultancy: Neon; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tvardi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: xCures; Advisory / Consultancy: Monopteros; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Genentech. L. Demidov:
v906 | Melanoma and other skin tumours
Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BIOCAD; Research grant / Funding (self): Amgen. D. Stroyakovskiy: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis. Z. Eroglu: Advisory / Consultancy: Array; Advisory / Consultancy: Regeneron; Research grant / Funding (institution): Novartis. P.F. Ferrucci: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis. J. Pigozzo: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD. P. Rutkowski: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Travel / Accommodation / Expenses: Orphan Drugs. J. Mackiewicz: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. I. Rooney: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. A. Voulgari: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. S. Troutman: Full / Part-time employment: Genentech. B. Pitcher: Full / Part-time employment: Roche. Y. Yan: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Genentech. J.M.G. Larkin: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Vitaccess: honoraria (self)/advisory/consultancy/travel: Achilles; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Covance: research grant (institution): AZ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Immunocore: research grant (institution): Boston Biomedical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Pharmacyclics: research grant (institution): BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Aveo: research grant (institution): Eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EUSA Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: GSK; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Imugene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: iOnctura; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Kymab; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Secarna.
LBA70
Talimogene laherparepvec (T-VEC) in combination (combo) with ipilimumab (ipi) versus ipi alone for advanced melanoma: 3-year landmark analysis of a randomized, open-label, phase II trial
J.A. Chesney1, I. Puzanov2, F. Collichio3, P. Singh4, M. Milhem5, J. Glaspy6, O. Hamid7, M.I. Ross8, P. Friedlander9, C. Garbe10, T. Logan11, A. Hauschild12, C. Lebbe13, M. Yi14, A. Sharma15, J.M. Mehnert16 1 James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA, 2 Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA, 3Clinical Research, The University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 4Medical Oncology, Mayo Clinic, Phoenix, AZ, USA, 5Medical Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA, 6School of Medicine, University of California Los Angeles, Los Angeles, CA, USA, 7Translational Research and Immunotherapy, The Angeles Clinic and Research Institute, Santa Monica, CA, USA, 8Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 9Icahn School of Medicine, Mount Sinai, New York, NY, USA, 10Division of Dermato-Oncology, Universitaets-Hautklinik Tuebingen, Tuebingen, Germany, 11School of Medicine, Indiana University, Indianapolis, IN, USA, 12Dermatology, UK-SH, Campus Kiel, Kiel, SchleswigHolstein, Germany, 13AP-HP Dermatology Cic Departments, Hoˆpital Saint Louis, Paris, France, 14Biostatistics, Amgen Inc., Thousand Oaks, CA, USA, 15Clinical Development, Amgen Inc., Thousand Oaks, CA, USA, 16Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA Background: This is the first and only randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor in advanced melanoma. Previously, the study met its primary endpoint: the combo of T-VEC plus ipi resulted in a significantly higher objective response rate (ORR) vs. ipi alone (39% vs. 18%; odds ratio, 2.9; 95% Cl, 1.5–5.5; P ¼ 0.002) (Chesney et al. J Clin Oncol. 2017). Here, we present results from the 3-year landmark analysis. Methods: Pts with unresectable, stages IIIB to IV melanoma were randomized 1:1 to receive the combo or ipi alone. T-VEC was injected intratumorally on day 1 of wk 1 at 106 plaque-forming units (PFU)/mL followed by subsequent doses at 108 PFU/mL on day 1 of wk 4, and every 2 wks thereafter. Intravenous ipi (3 mg/kg) was given every 3 wks starting on day 1 of wk 6 for up to 4 doses. Response was assessed by investigators per immune-related response criteria every 12 wks until disease progression. The primary endpoint was ORR; key secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. This analysis occurred 36 months (mos) after the last pt was randomized.
Volume 30 | Supplement 5 | October 2019
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A.M. Arance1, H. Gogas2, B. Dreno3, K.T. Flaherty4, L. Demidov5, D. Stroyakovskiy6, Z. Eroglu7, P.F. Ferrucci8, J. Pigozzo9, P. Rutkowski10, J. Mackiewicz11, I. Rooney12, A. Voulgari13, S. Troutman12, B. Pitcher14, Y. Yan15, J.M.G. Larkin16 1 Medical Oncology, Hospital Clınic Barcelona, Barcelona, Spain, 2School of Medicine, University of Athens, Athens, Greece, 3Department of Dermatology, CHU Nantes, Nantes, France, 4Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, 5Melanoma Unit, Department of General Surgery, Russian Oncological Research Centers, Moscow, Russian Federation, 6Chemotherapy, Moscow City Oncology Hospital N 62, Moscow, Krasnogorski District, Russian Federation, 7Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA, 8Unit of Oncology of Melanoma, European Institute of Oncology, Milan, Italy, 9 Department of Cutaneous Oncology, Melanoma Oncology Unit, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy, 10Department of Soft Tissue/Bone Sarcoma, The Maria Sklodowska Curie Memorial Cancer Centre and Institute of Oncology (MCMCC), Warsaw, Poland, 11Oddział Onkologii Klinicznej i Doswiadczalnej, Uniwersytet Medyczny w Poznaniu, Pozna n, Poland, 12Product Development, Oncology, Genentech, Inc., South San Francisco, CA, USA, 13Global Product Development Clinical Science, Roche Products Ltd, Welwyn Garden City, UK, 14Product Development, Oncology, Hoffmann-La Roche Ltd., Mississauga, AB, Canada, 15Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA, 16Department of Medicine, Royal Marsden Hospital NHS Foundation Trust, London, UK
Annals of Oncology
abstracts
Annals of Oncology
Disclosure: J.A. Chesney: Advisory / Consultancy, Travel / Accommodation / Expenses: Replimune; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Licensing / Royalties, Patents, Royalties, and Other Intellectual Property: University of Louisville. I. Puzanov: Advisory / Consultancy: 4SC; Advisory / Consultancy: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck. P. Singh: Advisory / Consultancy: AstraZeneca. M. Milhem: Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Amgen; Advisory / Consultancy: Trieza; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Biontech. O. Hamid: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi/Regeneron; Research grant / Funding (institution): Arcus; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): CytomX; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): Parker; Research grant / Funding (institution), Additional research funding for institution: Polynoma. : Pfizer. M.I. Ross: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Provectus; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Castle Biosciences. P. Friedlander: Advisory / Consultancy: Regeneron; Advisory / Consultancy: Puma Biosciences; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Aspyrian Therapeutics; Shareholder / Stockholder / Stock options: Incyte; Shareholder / Stockholder / Stock options: Clovis; Shareholder / Stockholder / Stock options: Merrimack Phamaceuticals; Shareholder / Stockholder / Stock options: Allergan. C. Garbe: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Neracare; Honoraria (self), Advisory / Consultancy: Philogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi. T. Logan: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Acceleron; Research grant / Funding (institution): Abbott; Research grant / Funding (institution): Abraxis; Research grant / Funding (institution): Argos; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Aveo; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Immatics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Synta; Research grant / Funding (institution): Threshold; Research grant / Funding (institution): Millenium; Honoraria (self), Research grant / Funding (institution), Additional research funding to institution disclosure: Tracon, Cerulean, EMD Serono, Macrogenic, Peloton, Iovance, MedImmune, Dynavax. : Prometheus. A. Hauschild: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD/Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Provectus; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Philogen; Advisory / Consultancy, Research grant / Funding (institution): Regeneron; Advisory / Consultancy: OncoSec. C. Lebbe: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self): Pierre-Fabre; Honoraria (self): Pfizer; Honoraria (self): Incyte; Officer / Board of Directors: Aventis. M. Yi: Shareholder /
Volume 30 | Supplement 5 | October 2019
Stockholder / Stock options, Full / Part-time employment: Amgen. A. Sharma: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. J.M. Mehnert: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EMD Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Polynoma; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Incyte. All other authors have declared no conflicts of interest.
LBA71
Phase II multicenter open label study of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study)
H. Jespersen1, R. Olofsson Bagge2, G. Ullenhag3, A. Carneiro4, H. Helgadottir5, I. Ljuslinder6, M. Levin1, C. All-Eriksson7, B. Andersson8, U. Stierner1, L.M. Nilsson9, J.A. Nilsson9, L. Ny1 1 Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden, 2 Sahlgrenska Academy, University of Gothenburg - The Sahlgrenska Academy, Go¨teborg, Sweden, 3Oncology, University Hospital Uppsala Akademiska Sjukhuset, Uppsala, Sweden, 4Oncology and Radiation Physics, Skane University Hospital, Lund, Sweden, 5Department of Oncology, Karolinska University Hospital, Stockholm, Sweden, 6 Department of Oncology, Norrlands University Hospital, Umea˚, Sweden, 7Department of Oncology, St. Erik Eye Hospital, Stockholm, Sweden, 8Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden, 9Surgery, University of Gothenburg - The Sahlgrenska Academy, Go¨teborg, Sweden Background: While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in patients with metastatic uveal melanoma. Reports of treatment with immune checkpoint inhibitors in monotherapy have been disappointing. There is preclinical evidence that the effect of immunotherapy may be augmented by epigenetic therapy through mechanisms including enhanced expression of HLA class I and cancer antigens, and suppression of myeloid suppressor cells. Methods: We performed a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD-1 inhibitor pembrolizumab and the HDAC inhibitor entinostat in 29 adult patients with metastatic uveal melanoma. Eligible patients had histologically confirmed metastatic uveal melanoma, ECOG performance status 0–1, and measurable disease as per RECIST 1.1. Patients received pembrolizumab 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Primary endpoint was objective response rate (ORR). Secondary endpoints include clinical benefit rate (CBR; CR, PR or SD) at 18 weeks, overall survival (OS), and safety assessed by adverse events (AE). Results: At the data cut off of June 21, 2019, 29 patients had been enrolled and received at least one dose of treatment with a median follow up of 7.7 months. Ninety per cent had liver metastases and 59% had received previous treatment for metastatic disease. A partial response (PR) was observed in 3 patients resulting in an ORR of 10%. Nine patients (31%) had a best overall response of stable disease (SD). Clinical benefit at week 18 was observed in 7 out of 29 patients (24%). Median OS was 11.5 months. Twenty-eight patients (97%) experienced treatment related AEs, and grade 3-4 AEs were reported in 18 patients (62%). There were no treatment related deaths. Conclusions: The PEMDAC study has demonstrated that combined HDAC- and PD1-inhibition can result in clinical efficacy in metastatic uveal melanoma with manageable toxicities. The obtained data warrant further investigation to address clinical and immunological characteristics of patients achieving clinical benefit. Clinical trial identification: NCT02697630 (Registered 3 March 2016). EudraCT: 2016-002114-50. Legal entity responsible for the study: Sahlgrenska University Hospital, V€astra Go¨taland Region. Funding: Syndax Pharmaceuticals and Merck & Co. Inc. Disclosure: R. Olofsson Bagge: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). G. Ullenhag: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). I. Ljuslinder: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). M. Levin: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). U. Stierner: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). L. Ny: Advisory / Consultancy: Merck & Co. Inc. (MSD Sweden). All other authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz394 | v907
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Results: 198 pts were randomized (98 to combo; 100 to ipi). As of 25 Feb 2019, the median follow-up time was 40.0 mos in the combo arm and 34.3 mos in the ipi arm. ORR was significantly higher with the combo vs. ipi alone (36.7% vs. 16.0%; odds ratio, 3.0; 95% CI, 1.6 to 6.0; P ¼ 0.002). Median PFS was 13.5 mos with combo and 4.5 mos with ipi (hazard ratio, 0.78; 95% Cl, 0.55–1.11; P ¼ 0.159). Median OS was not reached in either arm (HR, 0.85; 95% CI, 0.55–1.32; P ¼ 0.480). 45 pts (45.9%) in the combo arm and 64 pts (64%) in the ipi arm received subsequent anticancer therapy, with the median time from randomization to the first subsequent therapy being 27.7 mos and 8.3 mos, respectively. No new safety signals were detected. Conclusions: At the 3-year follow-up, T-VEC plus ipi combo continued to provide durable and statistically superior ORR compared with ipi alone. PFS was numerically longer with the combo than ipi. Survival is likely confounded by subsequent anticancer therapies (NCT01740297). Clinical trial identification: NCT01740297, release date December 4, 2012. Editorial acknowledgement: Medical writing assistance was provided by Yang Li (Amgen Inc). Legal entity responsible for the study: Amgen. Funding: Amgen.