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Poster Discussion session - Melanoma and other skin tumours

2134 - Talimogene laherparepvec (T-VEC) treatment increases intratumoral effector T-cell and natural killer (NK) cell density in noninjected tumors in patients (pts) with stage IIIB–IVM1c melanoma: evidence for systemic effects in a phase 2, single-arm study


20 Oct 2018


Poster Discussion session - Melanoma and other skin tumours


Clinical Research;  Immunotherapy

Tumour Site



Helen Gogas


Annals of Oncology (2018) 29 (suppl_8): viii442-viii466. 10.1093/annonc/mdy289


H. Gogas1, I. Samoylenko2, D. Schadendorf3, R. Gutzmer4, J.J. Grob5, J.J. Sacco6, K. Gorski7, A. Anderson7, C. Liu8, J. Malvehy9

Author affiliations

  • 1 First Department Of Medicine, Laiko General Hospital of Athens, 115 27 - Athens/GR
  • 2 Tumor Biotherapy, N.N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU
  • 3 Department Of Dermatology, University of Duisburg-Essen and German Cancer Consortium (DKTK), 45122 - Essen/DE
  • 4 Skin Cancer Center, Hannover Medical School, 30625 - Hannover/DE
  • 5 Service De Dermatologie, Aix Marseille University, and APHM University Hospital Timone, 13009 - Marseille/FR
  • 6 Medical Oncology, Clatterbridge Cancer Center, CH63 4JY - Wirral/GB
  • 7 Clinical Biomarkers, Amgen Inc., 91320 - Thousand Oaks/US
  • 8 Biostatistics, Amgen Inc., 91320 - Thousand Oaks/US
  • 9 Dermatology Department And Idibaps, Hospital Clinic of Barcelona, 8036 - Barcelona/ES


Abstract 2134


In the phase 3 OPTiM trial, overall response (OR) and durable response (DR: OR lasting ≥ 6 months) rates were 26.4% and 16.3%, respectively, in pts with advanced melanoma treated with T-VEC. The primary endpoint of this study was the correlation between baseline (BL) CD8+ density and OR. Key secondary and exploratory endpoints included correlation between BL CD8+ density and DR, efficacy, safety, and correlation of outcome with other biomarkers.


Pts with unresectable stage IIIB–IVM1c melanoma were treated with T-VEC at the approved dose. Tumor biopsies were collected at BL (n = 91) and week (W) 6 (n = 59) from uninjected lesions. All biopsies were analyzed for CD8+ density by immunohistochemistry. In a substudy of paired BL–W6 biopsies (n = 25), additional immunophenotypes were analyzed by multiparameter immunofluorescence (IF).


112 pts were enrolled; 111 received ≥ 1 T-VEC dose. BL CD8+ density did not predict OR (odds ratio, 95% CI; P value: 1.06, 0.83–1.34; 0.64) but correlated with DR (1.38, 1.00–1.88; 0.047). The median increase in tumor CD8+ density from BL to W6 was 2.4-fold (P < 0.0001). Intratumoral changes included an increase in effector CD8+ T-cells and NK cells but not macrophages (Table). In addition, tumorinfiltrating CD8+ T-cells had a memory phenotype (CD45RO+) and/or expressed immune checkpoint markers PD-1 and CTLA-4. Efficacy and safety were similar to OPTiM.Table: 1246PD

Changes in intratumoral density of immune-cell subsets*

Cell type, markersFold increaseP value
Helper T cells, CD3+ CD4+1.720.050
Effector CTL, CD3+ CD8+ granzyme B+3.100.005
Effector NK cells, CD3- CD56+ granzyme B+3.770.020
Macrophage, CD68+1.050.740

IF substudy included 25 paired BL–W6 biopsies


T-VEC treatment was associated with infiltrates of effector CD8+ T-cells and NK cells in uninjected lesions, indicating a systemic effect. BL tumor CD8+ density correlated with DR but not OR. Data also support studies of T-VEC combined with checkpoint inhibitors. Correlations of outcome with changes in other immune markers are under investigation.

Clinical trial identification

EudraCT: 2013-005552-15, Sponsor Protocol: 20120325

Legal entity responsible for the study

Amgen Inc.


Amgen Inc.

Editorial Acknowledgement

Medical writing was provided by Yang Li, Ph.D. (Amgen Inc.).


H. Gogas: Honoraria: BMS, MSD, Roche, Novartis, Amgen; Research funding: BMS, MSD, Roche, Novartis. I. Samoylenko: Consulting or advisory role, speakers’ bureau: BMS, MSD, Roche, Novartis, R-Farm; Research funding: BMS. D. Schadendorf: Honoraria, Consulting or advisory role: BMS, MSD, Roche, Novartis, Amgen, Pfizer, Sanofi; Speakers’ bureau: BMS, Roche, Novartis; Research funding (self and institution): BMS, Novartis. R. Gutzmer: Honoraria: BMS, MSD/Merck, Roche, Novartis, Amgen, GSK, Boehringer Ingelheim, AstraZeneca, Merck Serono, Pierre Fabre, Almirall; Consulting or advisory role: BMS, MSD/Merck, Roche, Novartis, Amgen, Merck Serono, Pierre Fabre, Almirall, LEO, Incyte, 4SC; Research funding (self and institution): Pfizer, Novartis, J&J; Travel, accomodations, expense: BMS, Roche, Pierre Fabre, Merck Serono. J.J. Grob: Consulting or advisory role: BMS, MSD, Roche, Novartis, Amgen, Merck, Pierre Fabre, Pfizer. J.J. Sacco: Honoraria: BMS; Consulting or advisory role: Immunocore; Research funding (self and institution): BMS, MSD, AstraZeneca, Immunocore, Amgen, Replimmune; Travel, accomodations, expense: BMS, MSD. K. Gorski, A. Anderson: Employee, Stock, Patents: Amgen. C. Liu: Employee, Stock: Amgen. J. Malvehy: Speakers’ bureau (self and immediate family member): BMS, Novartis, Amgen, Pierre Fabre, Leo Pharma, Almirall, MSD; Research funding (self, immediate family member, institution): BMS, Amgen, Leo Pharma, Almirall, GSK; Patents (self, immediate family member, institution): ISDIN.

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