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Poster discussion session - Immunotherapy of cancer 1

4635 - Clinical efficacy of T-cell therapy after short-term BRAF-inhibitor induction in checkpoint inhibitor resistant metastatic melanoma patients


20 Oct 2018


Poster discussion session - Immunotherapy of cancer 1


Targeted Therapy;  Immunotherapy

Tumour Site



Troels Borch


Annals of Oncology (2018) 29 (suppl_8): viii400-viii441. 10.1093/annonc/mdy288


T.H. Borch1, R. Andersen1, M.A.H. Rana1, P. Kongsted1, M. Pedersen1, M. Nielsen1, J.W. Kjeldsen1, A. Kverneland1, C.L. Lorentzen1, Ö. Met1, M. Donia2, I. Svane1

Author affiliations

  • 1 Center For Cancer Immunotherapy And Department Of Oncology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 2 Center For Cancer Immune Therapy And Department Of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, 2730 - Herlev/DK


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Abstract 4635


Only patients in good performance status can be offered treatment with adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) in metastatic melanoma (MM), and more than half of the treated patients do not obtain durable benefit. We hypothesized that pretreatment with vemurafenib (vem), a BRAF inhibitor with immunomodulatory properties, could prevent clinical deterioration while waiting for TILs and improve the immunological features of the TIL product. To this end we performed a clinical trial combining pretreatment with vemurafenib and TIL therapy.


In this phase II clinical trial patients were pretreated with vem for 7 days prior to tumor excision and for the following weeks while T-cells were manufactured. TILs were grown from tumor fragments in vitro and re-infused into the patient preceded by a lymphodepleting chemotherapy regimen and followed by interleukin-2 infusion. Vem was discontinued 7 days before TIL infusion. Primary endpoint was to evaluate feasibility and safety. Secondary endpoint was to evaluate clinical response rate.


A total of 13 patients with BRAF mutated MM were included following progression after anti-PD-1 and/or anti-CTLA-4 treatment. No unexpected toxicity was observed. Clinical response evaluation to combined treatment is still ongoing. So far the objective response rate is 82% (9/11) with one patient achieving ongoing complete response, eight patients achieved partial response (one ongoing), two achieved stable disease and one is not yet evaluated. One was excluded before treatment with TILs. Exploratory analyses indicate a correlation of baseline serum cytokines and duration of response. Final analysis of primary and secondary endpoints and comprehensive immune data will be presented*.


Pretreatment with vem before infusion of TILs was safe and feasible and induced objective clinical responses in this difficult-to-treat cohort of patients with MM resistant to checkpoint inhibitors. *Preliminary data from the trial in progress was presented at the SITC annual meeting (1,2) and ESMO IO 2017. 1. Borch TH et al. J Immunother Cancer 2014;2 (Suppl 3:P67) 2. Borch TH et al. J Immunother Cancer 2016;4 (Suppl 1:P131).

Clinical trial identification


Legal entity responsible for the study

Inge-Marie Svane.


Danish Cancer Society - The Capital Region of Denmark.

Editorial Acknowledgement


T.H. Borch: Honoraria for lectures: BMS; Travel support: BMS, Roche. M. Donia: Honoraria for lectures: Bristol-Myers Squibb, Sanofi-Genzyme, MSD, AstraZeneca. I.M. Svane: Honoraria or consultation fees: Roche, Novartis, Merck, MSD, Celgene, Incyte, Pfizer, BMS, AstraZeneca, TIL T Bio, IO Biotech; Restricted research grants: Incyte; Co-founder and stock owner: IO Biotech. All other authors have declared no conflicts of interest.

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