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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

1436 - Safety run-in evaluation of the phase I trial of trifluridine/tipiracil (FTD/TPI) in combination with oxaliplatin and a monoclonal antibody (bevacizumab or nivolumab) in patients (pts) with metastatic colorectal cancer (mCRC)


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Cytotoxic Therapy;  Clinical Research;  Immunotherapy

Tumour Site

Colon and Rectal Cancer


Aitana Calvo Ferrandiz


Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281


A. Calvo Ferrandiz1, L. Dahan2, A. Hollebecque3, G. Prager4, T. Andre5, G. Argiles Martinez6, R. Bordonaro7, A. Stein8, G. Tortora9, C. Leger10, N. Amellal11, J. Tabernero12

Author affiliations

  • 1 Medical Oncology Dept, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 2 Service D'hge Et D'oncologie, CHU La Timone Enfants, 13385 - Marseille/FR
  • 3 Drug Development Department (ditep: Département D'innovations Thérapeutiques Et Essais Précoces), Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4 Comprehensive Cancer Center Vienna, Medical University Vienna, 1090 - Vienna/AT
  • 5 Service D'oncologie Médicale, Sorbonne Université et Hôpital Saint-Antoine, 75 - Paris/FR
  • 6 Institute Of Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 7 S.c. Di Oncologia Medica Arnas, Azienda Ospedaliera Garibaldi, 95100 - Catania/IT
  • 8 Onkologie, Hämatologie, Kmt Mit Sektion Pneumologie, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, 20246 - Hamburg/DE
  • 9 U.o.c. Di Oncologia/policlinico G.b. Rossi, AOUI and University of Verona, 37134 - Verona/IT
  • 10 Oncology Medical Division, Servier France, 92284 - Suresnes/FR
  • 11 Oncology Medical Division, Servier, 92284 - Suresnes/FR
  • 12 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES

Abstract 1436


The addition of the monoclonal antibody bevacizumab to chemotherapy has shown survival benefits in pts with mCRC. Another potential strategy is to combine chemotherapy with immunotherapies to enhance antitumor effect of the immune system. In vivo studies have shown an increase in anti-tumor activity when combining FTD/TPI with oxaliplatin or bevacizumab; and an increase in tumor immunogenicity after treatment with FTD/TPI and oxaliplatin, leading to a better tumor response to anti-PD-1 exposure.


Further to the dose-escalation part (24 pts), the recommended dose (RD) was defined as FTD/TPI 35 mg/m² bid, days 1–5 q14, together with oxaliplatin 85 mg/m² (day 1). Safety data were collected during expansion part from 12 evaluable pts treated with the doublet at the RD with either nivolumab 3 mg/kg (n = 6) or bevacizumab 5 mg/kg (n = 6) administered at day 1. Pts were monitored for safety for the first 2 months of treatment before allowing further enrollment. Eligibility criteria included measurable disease, performance status (PS) 0-1, normal organ function, and progression after >1 prior anti-tumor therapy (excluding oxaliplatin).


Baseline characteristics were median age of 67 years (range 52 to 75 years); PS 0/1 (3/9 pts), male/female (8/4 pts); and colon/rectum (5/7 pts). Drugrelated adverse events (AEs) reported in ≥ 2 pts were neutropenia, diarrhoea, asthenia, and nausea; mainly (93%) grade 1-2. The most common grade 3 or 4 drugrelated event was neutropenia. Grade 1 neurotoxicity attributed to oxaliplatin was observed in 2 pts. No immune-related AE due to nivolumab were reported. Best overall response included 2 partial responses after 2 months of treatment (1 pt in bevacizumab cohort, 1 MSI-H pt in nivolumab cohort). Pharmacokinetics parameters for FTD/TPI were aligned with historical data.


The safety data showed that the two triplets were well tolerated. Expansion enrollment is continuing in both cohorts to confirm preliminary evidence of activity in a larger number of patients.

Clinical trial identification


Legal entity responsible for the study

Institut de Recherches Internationales Servier (I.R.I.S.).


Institut de Recherches Internationales Servier (I.R.I.S.).

Editorial Acknowledgement


A. Hollebecque: Lilly, Amgen; Travel expenses: Servier, Amgen. G. Prager: Advisory boards, Speakers fee: Servier, Roche, BMS, Taiho. T. Andre: Consulting, advisory fees, travel expenses: Roche/Genentech, Amgen, Bristol-Myers Squibb, Honoraria: Roche/Genentech, Sanofi, Baxter, Bayer, Bristol-Myers Squibb, Amgen, MSD Oncology, Servier, XBiotech, Novartis. R. Bordonaro: Honoraria, consulting or advisory role: Proacta, Sanofi; Speakers' bureau: Novartis, Roche, Sanofi; Travel, accommodations, expenses: Novartis, Roche, Bayer, Astellas. A. Stein: Consulting or advisory role: Amgen, Bristol-Myers Squibb, Merck KGaA, Roche; Speakers' bureau: Amgen, Bayer, Celgene, Lilly, Merck KGaA, Roche, Sanofi; Servier research funding: Merck KGaA (Inst), Roche (Inst), Sanofi (Inst); Travel, accommodations, expenses: Roche. G. Tortora: Consulting or advisory role: Celgene; Merck Serono; Travel, accommodations, expenses: Merck Serono; Roche. C. Leger, N. Amellal: Employee: Servier. J. Tabernero: Advisory boards: Bayer, Boehringer Ingelheim, Genentech/Roche, Lilly, MSD, Merck Serono, Merrimack, Novartis, Peptomyc, Roche, Sanofi, Symphogen, Taiho. All other authors have declared no conflicts of interest.

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