igrelimogene litadenorepvec (TILT-123) / Tilt Biotherap - LARVOL DELTA

Phase 1b study of igrelimogene litadenorepvec plus pembrolizumab and pegylated liposomal doxorubicin in platinum-resistant ovarian cancer: preliminary safety and efficacy results (ESMO 2026) - No abstract available

Clinical • P1 data • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

Oncolytic adenoviruses in humans, what have we learned from treatment of > 500 patients with viruses such as Oncos-102 and TILT-123? (ESGCT 2026) - No abstract available

Clinical • Oncolytic virus • Oncology

Immune-cytokine signature predicts survival in patients with advanced melanoma treated with oncolytic adenovirus TILT-123 and chemotherapy and IL-2-free adoptive TIL therapy. (PubMed, J Immunother Cancer) - P1 | "These findings provide mechanistic insights into TILT-123 combined with TIL therapy and propose future directions for biomarker-guided clinical studies."

First-in-human • IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • CD27 • CD8 • EGF • IFNG • IL2

Extended monitoring and biomarker analysis in metastatic melanoma patients treated with TIL therapy and conditioning-replacing igrelimogene litadenorepvec virotherapy: Pre-infusion immune cell and cytokine profiles associated with survival. (ASCO 2026) - P1, P1/2 | "Combining TILT-123 with TIL therapy was safe and produced meaningful clinical activity in checkpoint inhibitor-refractory melanoma, especially in patients with lower HGF and EGF at baseline and a higher presence of young memory T cells and NK cells. In this clinical set-up, adapting the inclusion exclusion criteria to select patients with those defined immune system features, could help improve efficacy beyond. This approach may substantially broaden the feasibility and accessibility of TIL-based immunotherapy, especially due to the omission of the toxic conditioning regimens."

Biomarker • Clinical • Immune cell • IO biomarker • Metastases • Melanoma • Solid Tumor • CD27 • CD8 • EGF • HGF • NCAM1 • PTPRC

Fully intravenous split-dose administration of the oncolytic adenovirus TILT-123 in advanced solid tumors. (PubMed, Mol Ther) - "Post-treatment biopsies confirmed virus presence and alterations in immune cell composition. These findings support further evaluation of intravenous TILT-123 administration in clinical trials."

IO biomarker • Journal • Fatigue • Oncology • Solid Tumor • IL2 • TNFA

PROTA: Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab (Phase 1a) and Pegylated Liposomal Doxorubicin (Phase 1b) as Treatment for Ovarian Cancer. (clinicaltrials.gov) - P1/2 | N=29 | Active, not recruiting | Sponsor: TILT Biotherapeutics Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Platinum resistant • Allergy • Fallopian Tube Cancer • Immunology • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

Clinical-immunological correlates in platinum resistant or refractory ovarian cancer patients treated with chimeric oncolytic adenovirus encoding TNFa and IL-2 (TILT-123) in combination with pembrolizumab (AACR 2025) - P1/2 | "These preliminary results identify a key role of circulating lymphocyte re-distribution and humoral immune response as markers of treatment benefit. Initial phenotyping implicates IgM producing plasma cells as a potentially relevant immune cell population. Additionally we observed a correlation between the coagulation cascade and OS."

Clinical • Combination therapy • Oncolytic virus • Platinum resistant • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL2 • TNFA

Immunological activity of oncolytic adenovirus encoding TNFα and IL-2 (TILT-123) in combination with pembrolizumab in platinum resistant or refractory ovarian cancer patients (AACR 2024) - P1, P1/2 | "Analysis of biological samples revealed insights into mechanism of action, including an immune profile predictive of clinical response. These results, together with those from four other trials (NCT04695327, NCT04217473, NCT06125197 and NCT05222932) set the stage for continued clinical evaluation of TILT-123."

Clinical • Combination therapy • IO biomarker • Oncolytic virus • Platinum resistant • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • CD4 • CD8 • FOXP3 • GZMB • IL2 • TNFA

Alistipes and Eggerthella shape the response to oncolytic adenovirus therapy in mice and humans through short-chain fatty acid metabolism. (PubMed, Oncoimmunology) - P1, P1/2 | "We investigated the gut microbiome of cancer patients following treatment with the oncolytic adenovirus igrelimogene litadenorepvec (Ad5/3-E2F-d24-hTNF-IRES-hIL2; TILT-123)...Finally, in a case study, we observed that adenovirus treatment resulted in increased Alistipes relative abundance and reduced Eggerthella relative abundance, indicating that adenovirus therapy may beneficially modulate the microbiome. Overall, our findings reveal a novel association between Alistipes, Eggerthella, and the therapeutic response to oncolytic adenovirus therapy, highlighting their potential as biomarkers or targets for microbiome-based interventions such as pre-, pro-, or postbiotics."

IO biomarker • Journal • Preclinical • Oncology

TILT-T776: A Phase I Open-Label, Dose-escalation Clinical Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus TILT-123 in combination with avelumab in injectable solid tumor patients (melanoma and SCCHN) refractory to or progressing after anti-PD(L)1 immunotherapy (clinicaltrialsregister.eu) - P1 | N=9 | Completed | Sponsor: TILT Biotherapeutics Oy | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

TUNIMO: TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 Monotherapy (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: TILT Biotherapeutics Ltd. | Recruiting ➔ Completed | N=18 ➔ 32 | Trial completion date: Mar 2025 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Enrollment change • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

TUNINTIL-2: TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 With Lymphocyte-depleting Chemotherapy and TILs in the Treatment of Melanoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: TILT Biotherapeutics Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Oncology • Solid Tumor

Dyslipidaemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumours. (PubMed, Mol Ther) - P1, P1/2 | "Collectively these findings show that dyslipidaemia-associated natural IgM enhances the therapeutic efficacy of TILT-123, via antibody-dependent enhancement. These findings may have broader implications for other oncolytic viruses, an emerging class of tumour immunotherapies."

IO biomarker • Journal • Dyslipidemia • Oncology • Solid Tumor

Extended follow-up and response markers from conditioning-free TIL therapy with oncolytic adenovirus TILT-123 in the TUNINTIL phase 1 trial for advanced melanoma (SMR 2025) - No abstract available

Metastases • Oncolytic virus • P1 data • Melanoma • Oncology • Solid Tumor

KEYNOTE-E46: Oncolytic Adenovirus TILT-123 With Pembrolizumab as Treatment for Refractory Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: TILT Biotherapeutics Ltd. | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Split-dose intravenous delivery of igrelimogene litadenorepvec enhances viral levels in blood and tumours compared with conventional intratumoral injection (ESMO-IO 2025) - P1 | "Prolonged circulation correlates with greater viral positivity and immune presence within tumours. Additionally, practical and clinical advantages over intratumoral delivery (less restricted population, reduced procedural risk and discomfort, fewer healthcare resources, etc) make this approach an attractive way to use igrelimogene litadenorepvec."

Oncology • CD4 • CD8

Intravenous oncolytic adenovirus encoding tumor necrosis factor and interleukin 2 with immunomodulatory metronomic cyclophosphamide in patients with advanced solid tumors (ESMO-IO 2025) - P1 | "Clinical trial identification NCT04695327. TILT-123 was detected in tumors by qPCR.Conclusions Combination treatment of fully i.v. oncolytic adenovirus TILT-123 and metronomic CP shows a tolerable safety profile in addition to early signs of efficacy. Transduction of tumors with fully intravenous delivery was observed."

Clinical • Immunomodulating • Metastases • Oncolytic virus • Eye Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • Uveal Melanoma • IL2 • TNFA

Natural IgM and dyslipidemia enhance the efficacy of tumor necrosis factor and interleukin-2 encoding oncolytic adenovirus in solid tumors (ESMO-IO 2025) - P1, P1/2 | "Validation in 58 additional patients confirmed the link between elevated serum oxLDL, prolonged survival, and positive imaging responses.Conclusions IgM antibodies that cross-react with both TILT-123 and oxLDL are linked to improved outcomes, potentially via antibody-dependent enhancement in hyperlipidemic patients. Elevated oxLDL may help identify optimal candidates for TILT-123, supporting immunometabolic biomarkers for personalized oncolytic therapy."

Clinical • Oncolytic virus • Oncology • Solid Tumor • IL2 • TNFA

Neutralizing antibodies as functional effectors and predictive biomarkers in oncolytic adenovirus therapy (ESMO-IO 2025) - P1, P1/2 | "This study investigates the kinetics, composition, and functional roles of nAbs, and association with overall survival (OS) and response rate in patients treated with TILT-123 (igrelimogene litadenorepvec), an Ad5/3 oncolytic adenovirus encoding tumor necrosis factor and interleukin-2.Methods Multiple serum samples from 59 patients enrolled in four TILT-123 clinical trials (NCT04695327, NCT04217473, NCT05271318, NCT05222932) were analyzed for anti-Ad5/3 nAbs using a cell-based functional neutralization assay...These results suggest a major role for nAbs beyond sole neutralization, and a potential use as biomarkers and future targets for enhancing virotherapy efficacy. Further analysis will be performed in larger upcoming cohorts and phase II trials."

Biomarker • IO biomarker • Oncolytic virus • Oncology • IL2 • TNFA

Biomarker insights and long-term outcomes of TILT-123 oncolytic adenovirus combined with tumor-infiltrating lymphocytes in refractory metastatic melanoma: results from the TUNINTIL phase 1 trial (SITC 2025) - P1 | "All approvals were obtained prior to inclusion of the first patient in the trial.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal."

Biomarker • IO biomarker • Metastases • Oncolytic virus • P1 data • Tumor-infiltrating lymphocyte • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • TNFA

PROTA: Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab (Phase 1a) and Pegylated Liposomal Doxorubicin (Phase 1b) as Treatment for Ovarian Cancer. (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: TILT Biotherapeutics Ltd. | N=76 ➔ 29

Enrollment change • Platinum resistant • Allergy • Fallopian Tube Cancer • Immunology • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

Novel tumor-infiltrating lymphocytes therapy in solid tumors: latest updates from 2025 ASCO annual meeting. (PubMed, Exp Hematol Oncol) - "Notably, innovative TIL-based monotherapies and combination regimens have provided durable clinical responses and survival benefits for patients with various solid tumors. This article summarizes recent advances in TIL therapy for solid tumors presented at the 2025 ASCO Annual Meeting, highlighting monotherapies such as Lifileucel, LM103, OBX-115, GT101, GT300, GT201, and HS-IT101, as well as combination strategies with the oncolytic adenovirus TILT-123 or pembrolizumab."

Journal • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor

Clinical correlations and long-term survival in PROTA: Platinum-resistant or refractory ovarian cancer treated with an oncolytic adenovirus encoding TNF and IL2 in combination with pembrolizumab (ESMO 2025) - P1/2 | "These results may help identify patients likely to benefit from combined TILT-123 and pembrolizumab. A phase 2 is ongoing (NCT05271318)."

Clinical • Combination therapy • IO biomarker • Oncolytic virus • Platinum resistant • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • IL2

Fully intravenous split-dose administration of oncolytic adenovirus TILT-123 in advanced solid tumors (ESMO 2025) - P1, P1/2 | "Conclusions Fully i.v. dosing of TILT-123 is feasible and results in tumor transduction and immune activation, warranting further evaluation. A phase 2 trial utilizing fully i.v. dosing is ongoing (NCT05271318)."

IO biomarker • Metastases • Oncolytic virus • Oncology • Solid Tumor • CD4 • CD8 • CXCL11 • CXCL9 • FASLG • IL18 • IL2 • TNFSF12

Oncolytic adenovirus encoding TNF and IL2 (TILT-123): from preclinical development to clinical trials with tumor infiltrating lymphocyte therapy and checkpoint inhibitors (ESGCT 2025) - No abstract available

Checkpoint inhibition • Oncolytic virus • Preclinical • Tumor-infiltrating lymphocyte • Oncology • IL2