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posted on 2024-09-03, 07:40 authored by Santeri A. Pakola, Katriina J. Peltola, James H.A. Clubb, Elise Jirovec, Lyna Haybout, Tatiana V. Kudling, Tuomo Alanko, Riitta Korpisaari, Susanna Juteau, Marjut Jaakkola, Jorma Sormunen, Jukka Kemppainen, Annabrita Hemmes, Teijo Pellinen, Mirte van der Heijden, Dafne C.A. Quixabeira, Claudia Kistler, Suvi Sorsa, Riikka Havunen, Joao M. Santos, Victor Cervera-Carrascon, Akseli Hemminki A, Response evaluation in all injected lesions, evaluated by CT. B, Response evaluation in all injected lesions, evaluated by PET. C, Response evaluation in allimaged non-injected lesions, evaluated by CT. D, Response evaluation in all imaged non-injected lesions, evaluated by PET. Best response shown for A–D if patient continued to extension. E, Intravenous dose given versus sum SUVmax change of measured lesions on day 78. F, Intratumoral dose given versus sum SUVmax change of measured lesions on day 78. G, Overall survival in the trial. H, Progressionfree survival in the trial. I, Time to progression in the trial. J, Swimmer plot of the patients enrolled in the trial. For E and F, linear fit shown with 95% confidence intervals shown with R2 for goodness of fit and P value for slope deviation from zero. For G–I, disease control defined with PET-based criteria and comparison of disease control and no disease control evaluated with Mantel–Cox Log-rank test. ***, P < 0.001; ****, P < 0.0001.
Funding
Helsinki University Hospital Research funds
Cancer Foundation Finland
Jane and Aatos Erkko Foundation
Red Cross Blood Service
Sigrid Juselius Finland
TILT Biotherapeutics Oy
European Commision
History
ARTICLE ABSTRACT
TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors.
TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AE), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers.
Twenty patients were enrolled, with a median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment-related AEs included fever (16.7%), chills (13.0%), and fatigue (9.3%). Ten patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST(20%of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking.
TILT-123 was safe and able to produce antitumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, and NCT06125197).See related commentary by Silva-Pilipich and Smerdou, p. 3649
