ThermoDox (lyso-thermosensitive liposomal doxorubicin) / Imunon - LARVOL DELTA

Next-generation therapies for hepatocellular carcinoma: CAR-T cell and anticancer peptide synergy. (PubMed, Int J Biol Macromol) - "Nanotherapeutics like PIR NPs, ThermoDox, and liposomal drug formulations improve drug stability, delivery, and specificity, providing controlled release and reduced toxicity. The integration of CAR-T therapy with ACPs, nanomedicine, and dual-checkpoint blockade such as tremelimumab-durvalumab, and nivolumab-ipilimumab demonstrate improved tumour regression and survival outcomes. Combination strategies that modulate ROS levels, inhibit angiogenesis, and utilize peptide-drug conjugates show promise in preclinical and early clinical studies. This review highlights the therapeutic synergy of next-generation peptide, cellular, and nanoplatform-based therapies in enhancing outcomes for advanced HCC."

IO biomarker • Journal • Review • Fibrosis • Gastroenterology • Hepatocellular Cancer • Hepatology • Immunology • Liver Cancer • Liver Cirrhosis • Liver Failure • Oncology • Solid Tumor • GPC3 • TP53

Heat-activated intravenous liposomal doxorubicin combined with mitomycin C hyperthermic intravesical chemotherapy (HIVEC) for treatment of bladder cancer. (PubMed, Int J Hyperthermia) - "To evaluate the safety and pharmacokinetics of lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox®) combined with mitomycin C (MMC) hyperthermic intravesical chemotherapy (HIVEC) as a potential treatment for non-muscle invasive bladder cancer. On day 28, cystoscopy demonstrated normal-appearing bladder lumen, and some vacuolated cells were observed on bladder wall histology. Intravenous LTLD combined with MMC HIVEC was feasible and well tolerated in swine."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A novel murine model of LITT for glioblastoma reveals tumor reduction, BBB permeabilization, and drug delivery via ThermoDox®. (PubMed, Drug Deliv Transl Res) - "The distribution of doxorubicin released from intravenously administered Thermodox® was also evaluated. We present a reproducible preclinical model of LITT that enables investigation of tumor ablation, immune modulation, and thermally triggered drug delivery. These findings support the use of LITT as a platform for combinatorial strategies in glioma treatment."

Journal • Preclinical • Brain Cancer • Glioblastoma • Glioma • Immune Modulation • Immunology • Oncology • Solid Tumor

Laser Interstitial Thermal Therapy for Targeted CNS Delivery of Chemotherapy: Pre-Clinical Results and Planned Clinical Trial (SNO 2025) - "Immediate fluorometric assays demonstrated targeted intraparenchymal doxorubicin release surrounding the zone of ablation in the hemisphere that received LITT + Thermodox. There were no clinical signs of systemic or neurotoxicity during the 7-day monitoring period. No additional cerebral edema was noted on surveillance imaging in the hemisphere that received LITT + Thermodox compared to the hemisphere with LITT alone."

Preclinical

Laser Interstitial Thermal Therapy for Targeted CNS Delivery of Chemotherapy: Pre-Clinical Results and Planned Clinical Trial (WFNOS 2025) - "Immediate fluorometric assays demonstrated targeted intraparenchymal doxorubicin release surrounding the zone of ablation in the hemisphere that received LITT + Thermodox. There were no clinical signs of systemic or neurotoxicity during the 7-day monitoring period. No additional cerebral edema was noted on surveillance imaging in the hemisphere that received LITT + Thermodox compared to the hemisphere with LITT alone."

Preclinical

Undertreated Volume and Tumor Morphology as Predictors of Outcome Following Thermal Ablation of 3-7 cm Hepatocellular Carcinoma. (PubMed, J Vasc Interv Radiol) - "The correlations between tumor-ablation zone overlap and local recurrence and survival suggests that 3D pre- and post-ablation image registration could aid in verification of adequate treatment coverage or to predict recurrence. Image assessment and registration with ablation may support standardization, tailored treatment approaches, and outcome prediction."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Thermosensitive liposomal doxorubicin combined with hyperthermic intravesical chemotherapy for treatment of non-muscle invasive bladder cancer (AUA 2025) - "Applying hyperthermia to intravesical mitomycin C (MMC) enhances drug penetration; however, drug deposition in the deep muscularis and serosa remains challenging. Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of liposome-encapsulated doxorubicin (DOX) that is released when exposed to mild hyperthermic temperatures (39-42°C)... Treatment with a combination of intravenous LTLD and HIVEC was feasible and well-tolerated and resulted in substantial accumulation of DOX in the bladder wall without thermal damage, offering a potentially synergistic approach that merits consideration for a clinical trial for NMIBC."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Ultrasound-assisted efficient targeting of doxorubicin to the tumor microenvironment by lyso-thermosensitive liposomes of varying phase transition temperatures. (PubMed, Eur J Pharm Sci) - "Premature drug release is the primary hindrance to the effective function of the lyso-thermosensitive liposomes (LTSLs) of doxorubicin (Dox), known as ThermoDox® for the treatment of cancer. Among various formulations, F25 (DPPC: MSPC: DSPE-mPEG2000: HSPC, 65:10:4:25) showed the highest cellular uptake at 42℃ and significantly improved the antitumor and survival efficacy in mice bearing C26 colon carcinoma in combination with ultrasonic HT compared to F0. Collectively, results demonstrated that optimizing the rigidity of the liposomal bilayers through the combinatorial selection of PLs of different transition temperatures could improve the plasma stability of the liposome, and hence ameliorate the outcome of therapy in assistance with an effective HT approach."

Biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Children's National Research Institute | N=14 ➔ 0 | Trial completion date: Dec 2025 ➔ Dec 2024 | Recruiting ➔ Withdrawn | Trial primary completion date: Dec 2025 ➔ Dec 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Ewing Sarcoma • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice. (PubMed, Int J Mol Sci) - "In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1)...The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3

A PILOT STUDY OF LYSO-THERMOSENSITIVE LIPOSOMAL DOXORUBICIN AND MAGNETIC RESONANCE-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND FOR TREATMENT OF RELAPSED OR REFRACTORY SOLID TUMORS (CTOS 2023) - P2 | "N/A, trials in progress"

Clinical • Oncology • Solid Tumor

Data demonstrating the in vivo anti-tumor efficacy of thermosensitive liposome formulations of a drug combination in pre-clinical models of breast cancer. (PubMed, Data Brief) - "Our group previously developed and characterized a thermosensitive liposome formulation of the heat shock protein 90 inhibitor alvespimycin as a companion therapeutic to a thermosensitive liposome formulation equivalent in composition to ThermoDox (i.e., ThermoDXR), with the goal of increasing the therapeutic index of doxorubicin as the combination was revealed to be highly synergistic in a panel of human breast cancer cell lines including MDA-MB-231 (Dunne et al., 2019). The data presented here further describes the effect of the doxorubicin (DXR) and alvespimycin (ALV) combination in vitro and in vivo. Specifically, the combination effect in mouse breast cancer 4T1 cells and the in vivo efficacy of this heat-activated chemotherapy combination in both immunocompromised (MDA-MB-231 tumor bearing female SCID mice) and immunocompetent (4T1 tumor bearing female BALB/c mice) models of breast cancer."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound. (PubMed, BMC Cancer) - P1 | "This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours."

Journal • P1 data • Anesthesia • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: AeRang Kim | N=34 ➔ 2 | Recruiting ➔ Terminated; low accrual

Enrollment change • Trial termination • CNS Tumor • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Neuroblastoma • Neuroendocrine Tumor • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2 | N=14 | Recruiting | Sponsor: Children's National Research Institute | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

PanDox: Targeted Doxorubicin in Pancreatic Tumours (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: University of Oxford | N=18 ➔ 0 | Trial completion date: Dec 2022 ➔ Mar 2023 | Recruiting ➔ Withdrawn | Trial primary completion date: May 2022 ➔ Mar 2023

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2 | N=14 | Recruiting | Sponsor: Children's National Research Institute | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Enrollment open • Trial completion date • Trial primary completion date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

Heat-Activated Doxorubicin Uptake Facilitated by Laser Interstitial Thermal Therapy (SNO 2022) - "Doxorubicin was identified in 100% of mice treated with LITT following ThermoDox administration which is in contrast with groups treated with LITT and PBS, sham and ThermoDox, and sham and PBS. Here, we show that heat-activated nanoparticles are disrupted through hyperthermia followed by the release of doxorubicin only in the presence of hyperthermia, which paves way for the clinical use of ThermoDox as adjunct chemotherapy following LITT in treatment-resistant GBM treatment."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Heat-Activated Doxorubicin Uptake Facilitated by Laser Interstitial Thermal Therapy (SNO 2022) - "Doxorubicin was identified in 100% of mice treated with LITT following ThermoDox administration which is in contrast with groups treated with LITT and PBS, sham and ThermoDox, and sham and PBS. Here, we show that heat-activated nanoparticles are disrupted through hyperthermia followed by the release of doxorubicin only in the presence of hyperthermia, which paves way for the clinical use of ThermoDox as adjunct chemotherapy following LITT in treatment-resistant GBM treatment."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Accord Healthcare Launches Generic Doxorubicin PEGylated Liposomal Concentrate (PRNewswire) - "Accord Healthcare today announced the launch of a generic Doxorubicin pegylated liposomal 2mg/ml concentrate for solution for infusion in the UK and Europe....The product is indicated: As monotherapy for patients with metastatic breast cancer, where there is an increased cardiac risk; For treatment of advanced ovarian cancer in women who have failed a first-line platinum-based chemotherapy regimen; In combination with bortezomib for the treatment of progressive multiple myeloma in patients who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplant; For treatment of AIDS-related Kaposi's sarcoma (KS) in patients with low CD4 counts (<200 CD4 lymphocytes/mm³) and extensive mucocutaneous or visceral disease."

Generic launch • Breast Cancer • Gynecologic Cancers • Hematological Malignancies • Kaposi Sarcoma • Multiple Myeloma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor

Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin. (PubMed, Front Pharmacol) - "By using thermally sensitive lysolipids in its bilayer composition, ThermoDox implemented a heat-induced controlled release of DOX. Being folate-targeted, in vitro DFPML antitumoral activity is higher (IC ≈ 1 μg/ml) for folate receptor-overexpressing B16F10 murine melanoma cells, compared to MCF7 human breast adenocarcinoma cells (IC ≈ 4 μg/ml). Taken together, our results indicate that DFPML are strong candidates for folate-targeted anticancer therapies based on DOX controlled release."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor

EURO-DIGNITY: Heat-Activated Target Therapy of Local-Regional Relapse in Breast Cancer Patients (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Celsion | N=70 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Breast Cancer • Oncology • Solid Tumor

A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors (clinicaltrials.gov) - P1; N=34; Recruiting; Sponsor: AeRang Kim; Trial completion date: Oct 2021 ➔ Oct 2022; Trial primary completion date: Oct 2021 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Neuroblastoma • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • MRI

Turning down the heat: The case for mild hyperthermia and thermosensitive liposomes. (PubMed, Nanomedicine) - "The OPTIMA trial, as it was known, evaluated their thermosensitive liposome (TSL) formulation of doxorubicin (ThermoDox®) in combination with radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). As formulation scientists working in the field, we continue to believe that heat-triggered drug delivery platforms have tremendous potential as chemotherapy. Herein, we highlight potential limitations in the design of many of the Thermodox clinical trials, and we propose that despite these setbacks, TSLs have the potential to become an effective component of cancer therapy."

Clinical • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2; N=14; Not yet recruiting; Sponsor: Children's National Research Institute; Initiation date: Oct 2021 ➔ Feb 2022

Clinical • Trial initiation date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • MRI