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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, Trial outline. B, Lymphocyte changes after TILT-123, all cohorts pooled. C, Leukocyte changes after TILT-123, all cohorts pooled. D, Neutrophil changes after TILT-123, all cohorts pooled. E, Virus detection in blood by qPCR, before treatment, 1 hour post-treatment and 16 hours post-treatment, all dose cohorts available pooled (N = 10 patients). F, Virus detection in blood by qPCR 1 hour after intravenous dose, stratified by intravenous dose given. G, Virus detection in blood by qPCR 1 hour after intratumoral dose, stratified by intratumoral dose given. For all graphs, mean ± SEM shown. For B–D, P value from two-sided t test shown for graphs. LLOQ, lower limit of quantification; ns, non-significant (P > 0.05); *, P < 0.05; ****, P < 0.001.
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
