98TiP - T-cell therapy in combination with vemurafenib in BRAF mutated metastatic melanoma patients (98TiP)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Central Nervous System Malignancies
Presenter Troels Borch
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors T.H. Borch1, R. Andersen1, M.A.H. Rana2, P. Kongsted3, M. Pedersen1, M. Nielsen1, J.W. Kjeldsen1, A. Kverneland1, Ö. Met1, M. Donia1, I.M. Svane1
  • 1Center For Cancer Immune Therapy, Department Of Haematology And Department Of Oncology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 2Center For Cancer Immune Therapy, Department Of Haematology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 3Department Of Oncology, Herlev and Gentofte Hospital, 2730 - Herlev/DK



Adoptive T-cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has proven to be a powerful treatment option for patients with metastatic melanoma with response rates of approximately 50% and durable complete responses in about 15%. However, there is still a need for improving TIL efficacy and a promising strategy is combination with immunomodulating agents. One such is vemurafenib (vem), a selective BRAF inhibitor, which induces objective responses in about 50% of melanoma patients with tumors expressing BRAFV600E/K. In addition to the direct anti-cancer effect, vem has been shown to increase T-cell infiltration into tumors, upregulate melanoma antigen expression and increase the frequency of TIL recognizing autologous melanoma cells. This trial was previously presented at the Society for Immunotherapy of Cancer annual meeting (1,2). Updated data on clinical responses and preliminary immunological analyses will be presented.

Trial design

A total of 12 patients will be included in this open phase II non-randomized trial primarily to investigate safety when combining ACT and vem (ClinicalTrials.gov ID NCT02354690). Secondarily, clinical responses will be evaluated according to RECIST and extensive immune monitoring will be performed. Patients are treated with vem orally 960 mg BID one week prior to excision of tumor material for T-cell generation and continue vem until hospital admission (4-7 weeks). During hospitalization patients will receive a preparative lymphodepleting regimen consisting of cyclophosphamide 60 mg/kg for 2 days and fludarabine 25 mg/m2 for 5 days. TIL infusion consists of 5-10 x 1010 T-cells and patients are subsequently treated with continuous interleukin-2 infusion following the decrescendo-regimen for 5 days. Patients are evaluated for up to 5 years or until progression. 1. Borch TH, Andersen R et al. T cell therapy in combination with Vemurafenib in BRAF mutated metastatic melanoma patients. J Immunother Cancer. 2014;2 (Suppl 3:P67). 2. Borch TH, Andersen R et al. T cell therapy in combination with Vemurafenib in BRAF mutated metastatic melanoma patients. Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P131.

Clinical trial identification


Legal entity responsible for the study

Inge Marie Svane


Danish Cancer Society The Research Foundation of the Capital Region of Denmark


T.H. Borch: Honorarium for lecture from BMS. M. Donia: Honorarium from Genzyme, MSD, BMS. Received travel suppoer from Novartis, MSD, BMS, Roche and Pfizer. I.M. Svane: Advisory board memberships and lectures: Roche, Novartis, MSD, Celgene, Incyte, TILT bio, Pfizer, BMS, AstraZeneca. Institution has received limited grants for translational research from BMS, Roche, Novartis. All other authors have declared no conflicts of interest.