Feasibility, safety and efficacy of human intra-tumoral immuno-therapy. Gustave Roussy's initial experience with its first 100 patients.

Many intratumoural (IT) immunotherapies are currently developed in the clinic with the aim of overcoming primary and secondary resistance and/or to limit on-target/off-tumour toxicities of immune checkpoint targeted therapies. This study aimed to describe the feasibility, safety and efficacy of IT immunotherapy treatments. This retrospective single-centre study included the first 100 consecutive patients enrolled in Gustave Roussy's Human IntraTumoral-ImmunoTherapy (HIT-IT) program. Patient characteristics, target description, image guidance, safety and response according to iRECIST (Response Evaluation Criteria in Solid Tumours for immunotherapy trials) were recorded. Predictive factors of complications and responses were analysed. Survival was also reported. From 09/2015 to 05/2020, 100 patients had 115 tumours injected during 423 treatment cycles. Most frequent primary tumour arose from the skin (n = 49), digestive track (n = 4) or head and neck (n = 8). Injected tumours' mean diameter was 37 ± 23 mm, and a median number of 4 IT injections per patient (interquartile range:3-5) were performed. Targeted tumours for IT injections were superficial lymph nodes (36.5%), subcutaneous lesions (25.2%), liver tumours (20.9%) and others (17.4% including tumour sites such as deep lymph nodes or lung). Most patients (72%) received systemic immunotherapy in combination with HIT-IT. Procedure- and drug-related adverse events (AEs) occurred in 11.3% and 33.3% of the treatment cycles, respectively. Only 3 procedure-related AEs were grade-3 (0.7%); and no grade-4 or 5 occurred. Among all cycles, 7 grade-3 and 1 grade-5 drug-related AEs were reported. Complete and partial responses were achieved for 5% and 18% of patients, respectively, while stable disease was the best response for 11%. Patients receiving HIT-IT as a 1st-line treatment (24%), or not previously pre-treated with immunotherapy (53%) responded better, p = 0.001 and p = 0.004, respectively. From 1st cycle of IT, 12-month overall progression-free survival and overall survival were 21% (14-31%) and 57% (47-68%), respectively. This retrospective study, conducted on patients with cancer and treated within clinical trials at Gustave Roussy, demonstrates the feasibility and safety of the IT immunotherapy strategy.

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Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lambros Tselikas received honoraria from the following companies: Amgen, Boston Scientific, Medincell, GE Healthcare, Guerbet, SIRTEX, Quantum Surgical, and received grants from BMS foundation and Terumo. Thierry de Baere, has consulted or received advisory fees from: AstraZeneca, Boston Scientific, Eisai, GE Healthcare, Guerbet, Johnson & Johnson, Medtronic, Nanobiotix, Roche, Terumo, Quantum surgical, Frédéric Deschamps, has received honoraria from: Ablatech, Boston Scientific, General Electric, Medtronic and Terumo. Capucine Baldini, reports research funding from BMS, honoraria from Sanofi, BMS, Astra Zeneca, and Abbvie Jean-Charles Soria, received honoraria from Astex, AstraZeneca, Bayer, Blend Therapeutics, Boehringer-Ingelheim, Clovis, Eli Lily, Gammamabs, Merus, Mission Therapeutics, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Symhogen, Tarveda; is a Gritstone stockholder and was an AstraZeneca full time employee from Sept 2017 to Dec 2019 and is an AMGEN full time employee since July 2021. Fabrice Barlesi, reports personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda. Christophe Massard, has consulted or received advisory fees from: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi and Orion. Caroline Robert, has consulted for BMS, Pierre Fabre, Novartis, Amgen, Merck, MSD, Roche, Sanofi, Biothera, Ultimovacs. Stéphane Champiat, has received honoraria or consulted for the following companies: Amgen, AstraZeneca, BMS, Janssen, MSD, Novartis and Roche. Aurélien Marabelle, has participated to Scientific Advisory Boards or Consulted for the following companies: MSD, Astra Zeneca/Medimmune, Bayer, Pillar Partners, Bioncotech, Rigontec, Curevac, Servier, Amgen. Antoine Dardenne, , Matthieu Faron, , Samy Ammari, Siham Farhane, Steve Suzzoni, François-Xavier Danlos, Thibault Raoult, Sandrine Susini, Nael Al-Shatti, Severine Mouraud, Adrian Kobe, Alexandre Delpla, Charles Roux, have no conflict of interest to declare •No specific funding was obtained for this study. The Intratumoral programm of Gustave Roussy is partially funded by the Centre d’Investigation Clinique BIOTHERIS (CIC1428 INSERM)