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DRUG:

igrelimogene litadenorepvec (TILT-123)

i
Other names: TILT-123, Ad5/3-E2F-d24-hTNFa-IRES-hIL2, TNFalpha and IL-2 coding oncolytic adenovirus, PM1016
Associations
Company:
Biotheus, Tilt Biotherap
Drug class:
IL-2 stimulant, TNFα stimulant
Related drugs:
Associations
15d
Single intravenous administration of oncolytic adenovirus TILT-123 results in systemic tumor transduction and immune response in patients with advanced solid tumors. (PubMed, J Exp Clin Cancer Res)
TILT-123 demonstrated safety and significant intratumoral immunomodulation following a single i.v. administration, warranting further investigation.
Journal • Oncolytic virus • IO biomarker • Metastases
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
6ms
PROTA: Oncolytic Adenovirus Coding for TNFa and IL2 (TILT-123) With Pembrolizumab or Pembrolizumab and Pegylated Liposomal Doxorubicin as Treatment for Ovarian Cancer. (clinicaltrials.gov)
P1, N=29, Recruiting, TILT Biotherapeutics Ltd. | Trial completion date: Mar 2026 --> Jan 2027 | Trial primary completion date: Jun 2024 --> Jan 2025
Trial completion date • Trial primary completion date
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Keytruda (pembrolizumab) • pegylated liposomal doxorubicin • igrelimogene litadenorepvec (TILT-123)
8ms
Safety, efficacy, and biological data of T cell-enabling oncolytic adenovirus TILT-123 in advanced solid cancers from the TUNIMO monotherapy phase I trial. (PubMed, Clin Cancer Res)
TILT-123 was safe and able to produce anti-tumor 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, NCT06125197).
P1 data • Journal • Oncolytic virus • Metastases
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
8ms
Oncolytic Adenovirus TILT-123 With Pembrolizumab as Treatment for Refractory Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1, N=22, Recruiting, TILT Biotherapeutics Ltd. | Not yet recruiting --> Recruiting | Initiation date: Nov 2023 --> Mar 2024
Enrollment open • Trial initiation date • Combination therapy • Oncolytic virus • Checkpoint inhibition
|
Keytruda (pembrolizumab) • igrelimogene litadenorepvec (TILT-123)
8ms
TUNINTIL: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma (clinicaltrials.gov)
P1, N=17, Active, not recruiting, TILT Biotherapeutics Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: May 2023 --> Dec 2023
Enrollment closed • Trial primary completion date • Oncolytic virus • Metastases
|
BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
8ms
TUNIMO: TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 Monotherapy (clinicaltrials.gov)
P1, N=18, Recruiting, TILT Biotherapeutics Ltd. | Trial primary completion date: Dec 2023 --> Sep 2024
Trial primary completion date • Oncolytic virus
|
igrelimogene litadenorepvec (TILT-123)
1year
New P1 trial • Combination therapy • Oncolytic virus • Checkpoint inhibition
|
Keytruda (pembrolizumab) • igrelimogene litadenorepvec (TILT-123)
1year
Immune cell profiling of advanced-stage solid tumors patients treated with an oncolytic adenovirus encoding for TNF-a and IL-2 (TILT-123) (SITC 2023)
A detailed immunological profile will be presented. Conclusions Treatment with TILT-123 oncolytic adenovirus changes the profile of immune cells circulating systemically and locally infiltrating injected and non-injected tumor sites.
Clinical • Oncolytic virus • Metastases • Immune cell
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
1year
Early phase oncology experience on the use of an oncolytic adenovirus encoding for TNFa and IL-2 for the treatment of solid tumors – Interim results (SITC 2023)
Pharmacokinetics, biosafety as well as biological correlates are being studied. Conclusions Accumulating evidence indicates that TILT-123 with immunotherapy is safe and shows signs of antitumor activity, thus endorsing further clinical development.
Oncolytic virus
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
1year
Enhancing anti-tumor response in ICI-refractory non-small cell lung cancer through intravenous administration of oncolytic adenovirus armed with hTNFα and hIL-2 in combination with aPD-1 blockade (SITC 2023)
TILT-123), a serotype chimeric oncolytic adenovirus armed with tumor necrosis factor alpha (hTNFα) and interleukin 2 (hIL-2), administered intravenously...Conclusions Our findings highlight the potential of intravenously delivered oncolytic adenovirus armed with hTNFα and hIL-2 in combination with aPD-1 checkpoint blockade to overcome checkpoint resistance and improve treatment outcomes in advanced NSCLC. This approach is promising for addressing the major unmet clinical need in patients with checkpoint refractory/resistant NSCLC and supports further investigation in clinical trials.
Combination therapy • Oncolytic virus
|
CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
over1year
Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer. (PubMed, Oncoimmunology)
Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Checkpoint block
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
over1year
Emerging Data from the Use of TILT-123, an Oncolytic Adenovirus Armed with TNFa and IL-2 in Patients with Solid Tumors (ASGCT 2023)
Since 2020, four Phase I studies have been initiated: a monotherapy (NCT04695327) and combinations with TILs (NCT04217473), pembrolizumab or avelumab (NCT05271318, NCT05222932). Likewise, analysis of tumor samples revealed increasing diversity of CD8 and CD4 T lymphocyte subsets.Emerging data from clinical trials suggests that TILT-123 has an adequate safety profile and can reshape the tumor microenvironment resulting in antitumor activity, at the tested doses. Studying biological samples allowed a better understanding on the mechanism of action of this gene therapy product.
Clinical • Oncolytic virus
|
CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • CXCL11 (C-X-C Motif Chemokine Ligand 11) • CCL3 (C-C Motif Chemokine Ligand 3)
|
Keytruda (pembrolizumab) • Bavencio (avelumab) • igrelimogene litadenorepvec (TILT-123)
over1year
TUNINTIL: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma (clinicaltrials.gov)
P1, N=15, Recruiting, TILT Biotherapeutics Ltd. | Trial primary completion date: Oct 2023 --> May 2023
Trial primary completion date • Oncolytic virus • Metastases
|
BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
over1year
TUNINTIL: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma (clinicaltrials.gov)
P1, N=15, Recruiting, TILT Biotherapeutics Ltd. | Trial primary completion date: Oct 2022 --> Oct 2023
Trial primary completion date • Oncolytic virus • Metastases
|
BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
over1year
Development of a Syrian hamster anti-PD-L1 monoclonal antibody enables oncolytic adenoviral immunotherapy modelling in an immunocompetent virus replication permissive setting. (PubMed, Front Immunol)
Supernatants from hybridoma parent subclone 11B12B4 provided the highest positive PD-L1 signal, on Syrian hamster PBMCs and three cancer cell lines (HT100, HapT1 and HCPC1). Novel Syrian hamster anti-PD-L1 clone 11B12-1 induces tumour growth control in a hamster model of PDAC. Combining 11B12-1 with oncolytic adenovirus TILT-123 improves tumour growth control further and demonstrates good safety and toxicity profiles.
Journal • Oncolytic virus
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
PD-L1 expression
|
igrelimogene litadenorepvec (TILT-123)
2years
Immunological analysis of blood from patients with solid tumors treated with TILT-123, an oncolytic adenovirus encoding for tumor necrosis factor alpha (TNFa) and interleukin 2 (IL-2) (ESMO-IO 2022)
Immunological data (e.g. flow cytometry and/or cytokine data) will be presented. Conclusions TILT-123 can induce systemic immunological effects supporting the continued development of the agent as cancer immunotherapy.
Clinical • Oncolytic virus
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
2years
Emerging results from the use of an Oncolytic Adenovirus armed with TNFa and IL-2 (TILT-123) in different Phase I Solid Tumor Clinical trials (SITC 2022)
Background After the first Immune Checkpoint Inhibitor (ICI) was approved (ipilimumab, 2011 for cancer therapy, the list of indications routinely treated with ICIs keeps increasing. Conclusions Preliminary data emerging from Phase I clinical trials using TILT-123, point to an adequately safe approach able to induce antitumor activity, both as monotherapy and in combination. Dose escalation continues in pursuit of a recommended dose to use in Phase II clinical trials.
Clinical • P1 data • Oncolytic virus
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
Yervoy (ipilimumab) • igrelimogene litadenorepvec (TILT-123)
over2years
Bioprocess Development of TILT-123 Oncolytic Adenovirus: From R&D Scale to cGMP Manufacturing (ASGCT 2022)
All the process and product-related impurities were within the specification range required by the regulatory authorities. The technology transfer run was used to supply biodistribution and toxicity studies, the Engineering run is currently being used for quality control development and as reference material, while GMP manufacturing campaigns are being used to supply a clinical trial.
Oncolytic virus
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
over2years
First-in-human clinical trial of an oncolytic adenovirus armed with TNFa and IL-2 in patients with advanced melanoma receiving adoptive cell transfer of tumor-infiltrating lymphocytes. (ASCO 2022)
TILT-123 is an oncolytic adenovirus (Ad5/3-E2F-D24-TNFa-IRES-IL2) designed to enable T-cell therapies and checkpoint inhibition against cancer...Cohorts 1-3 have been completed without DLTs. Enrollment in cohort 4 was initiated in December 2021.
Clinical • P1 data • Oncolytic virus • Tumor-Infiltrating Lymphocyte
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
almost3years
TUNINTIL: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma (clinicaltrials.gov)
P1, N=15, Recruiting, TILT Biotherapeutics Ltd. | Trial completion date: May 2022 --> Dec 2024 | Trial primary completion date: Jan 2022 --> Oct 2022
Clinical • Trial completion date • Trial primary completion date • Oncolytic virus
|
BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
3years
TUNINTIL: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma (clinicaltrials.gov)
P1, N=15, Recruiting, TILT Biotherapeutics Ltd. | Trial completion date: Jul 2021 --> May 2022 | Trial primary completion date: May 2021 --> Jan 2022
Clinical • Trial completion date • Trial primary completion date • Oncolytic virus
|
BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
over3years
[VIRTUAL] A phase I, first-in-human, study of TILT-123, a tumor-selective oncolytic adenovirus encoding TNFa and IL-2, in participants with advanced melanoma receiving adoptive T-cell therapy with tumor-infiltrating lymphocytes (ESMO 2021)
. Secondary endpoints include evaluation of safety and tolerability for the duration of the trial, antitumor efficacy, antitumor responses, and biological effects against tumors. Enrollment began in 2020 and, at the time of submission, cohort 1 was completed without DLTs, and cohort 2 enrolment is in progress.
P1 data • Oncolytic virus • Tumor-Infiltrating Lymphocyte
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)
almost4years
Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1. (PubMed, Cells)
The virus is rapidly cleared from healthy tissues, and it does not cause damage to vital organs. The results support the initiation of a phase 1 dose-escalation trial, where melanoma patients receiving a tumor-infiltrating lymphocyte therapy are treated with TILT-123 (NCT04217473).
Journal • Combination therapy • Checkpoint inhibition
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
|
TILs
|
igrelimogene litadenorepvec (TILT-123)
4years
Oncolytic adenovirus shapes the ovarian tumor microenvironment for potent tumor-infiltrating lymphocyte tumor reactivity. (PubMed, J Immunother Cancer)
Overall, oncolytic adenovirus Ad5/3-E2F-D24-hTNFa-IRES-hIL2 was able to rewire the ovarian tumor microenvironment to accommodate heightened antitumor TIL reactivity. Such effects may improve the clinical effectiveness of ACT with TILs in patients with advanced OVCA.
Journal • Tumor-Infiltrating Lymphocyte • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • IL2 (Interleukin 2)
|
PD-L1 expression • TILs
|
igrelimogene litadenorepvec (TILT-123)
4years
Tumor microenvironment remodeling by an engineered oncolytic adenovirus results in improved outcome from PD-L1 inhibition. (PubMed, Oncoimmunology)
When Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (an oncolytic adenovirus coding for TNFa and IL-2, also known as TILT-123) and checkpoint inhibitors were used together in fresh urological tumor histocultures, a significant shift toward immune activity (not only tumor necrosis alpha and interleukin-2 but also interferon gamma and granzyme B) and increased T-cell trafficking signals (CXCL10) was observed...To conclude, when an engineered oncolytic adenovirus was utilized to modify the tumor microenvironment towards what meta-analyses have pointed as predictive markers for checkpoint inhibitory therapy, the response to them increased synergistically. Of note, key findings were confirmed in fresh patient-derived tumor explants.
Journal • PD(L)-1 Biomarker
|
IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • IL2 (Interleukin 2) • GZMB (Granzyme B)
|
igrelimogene litadenorepvec (TILT-123)
over4years
Clinical • Enrollment open • Oncolytic virus
|
BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
|
TILs
|
igrelimogene litadenorepvec (TILT-123)
5years
Revamping the ovarian tumour microenvironment with an oncolytic adenovirus yields enhanced tumour-infiltrating lymphocyte anti-tumour activity (ESMO-IO 2019)
Hence, we hypothesized that an oncolytic adenovirus expressing Tumour Necrosis Factor (TNF)-alpha(a) and Interleukin (IL)-2 (Ad5/3-E2F-D24-hIL-2-IRES-TNFa; TILT-123) could overcome this by generating a proinflammatory microenvironment and reinvigorating TIL anti-tumour activity... These data illustrate the potential of oncolytic adenovirus coding for TNFa and IL-2 to rewire the ovarian tumour microenvironment for effective TIL anti-tumour reactivity. This approach may improve the efficacy of adoptive TIL therapy in ovarian cancer patients, thus warranting further clinical investigation.Legal entity responsible for the study: TILT Biotherapeutics Ltd. Funding: TILT Biotherapeutics Ltd.
Tumor-Infiltrating Lymphocyte
|
IFNG (Interferon, gamma) • IL2 (Interleukin 2)
|
igrelimogene litadenorepvec (TILT-123)