Lipotecan (TLC388) / Taiwan Liposome Company - LARVOL DELTA

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy. (PubMed, Cancer Immunol Immunother) - "The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer."

Combination therapy • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • STING

Topoisomerase I Inhibition Radiosensitizing Hepatocellular Carcinoma by RNF144A-mediated DNA-PKcs Ubiquitination and Natural Killer Cell Cytotoxicity. (PubMed, J Clin Transl Hepatol) - "Orthotopic xenografts were treated with Lipotecan and/or RT...TOP1i reinforces NK cell-activated anti-HCC effect of RT through RNF144A mediated DNA-PKcs ubiquitination. RNF144A provides a reason for differentiating radiosensitization effect between HCC cells."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • MICA • MICB • TOP1

An open label, single-arm, two-stage, multicenter, phase II study to evaluate the efficacy and safety of TLC388 as second-line treatment in subjects with poorly differentiated neuroendocrine carcinomas (TCOGT1Z14). (ASCO 2019) - P2; "...Camptothecin analogs, like topotecan and irinotecan, are approved chemotherapy in small cell lung cancer (SCLC)...Patients aged 20 years or older enrolled between July 2015 to May 2018 had confirmed metastatic NEC with prior systemic therapy with etoposide plus cisplatin... TLC388 shows modest antitumor activity in metastatic NEC. Clinical trial information: NCT02457273"

Clinical • P2 data

Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy. (PubMed, Cancers (Basel)) - "Lipotecan thereby increases cancer immunogenicity and triggers an antitumor immune response to attract immune cell infiltration within the tumor microenvironment (TME) in vitro and in vivo. Taken together, these results show that lipotecan can remodel the tumor microenvironment to provoke anticancer immune responses, which can provide potential clinical benefits to the therapeutic efficacy of neoCRT in LARC patients."

Clinical • Immunogenic cell death • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor • HMGB1

Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2; N=62; Recruiting; Sponsor: Taiwan Liposome Company

New P2 trial • Biosimilar • Hepatocellular Cancer • Oncology

TLC388 Induces DNA Damage and G2 Phase Cell Cycle Arrest in Human Non-Small Cell Lung Cancer Cells. (PubMed, Cancer Control) - "TLC388, a camptothecin-derivative targeting topoisomerase I, is a potential anticancer drug. TLC388 inhibits NSCLC cell growth by inflicting DNA damage and activating G2/M checkpoint proteins that trigger G2 phase cell cycle arrest to enable DNA repair. CHIR124 enhanced the cytotoxic effect of TLC388 and induced apoptosis."

Journal • Ataxia • CNS Disorders • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • CCNB1 • CDK1 • CHEK2 • TOP1

An Open-Label, Single-Arm, Two-Stage, Multicenter, Phase II Study to Evaluate the Efficacy of TLC388 and Genomic Analysis for Poorly Differentiated Neuroendocrine Carcinomas. (PubMed, Oncologist) - P2; "Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive. Currently, effective therapeutic options for treating metastatic poorly differentiated NECs beyond platinum-based chemotherapy remain elusive. In this single-arm, multicenter, phase II study, 23 patients with NEC were enrolled and received TLC388 (Lipotecan) Hydrochloride, which is a novel camptothecin analog. The results demonstrated the disease control rate of 15%, the median progression-free survival of 1.8 (95% confidence interval [CI], 0.4-15) months, and the median overall survival of 4.3 (95% CI, 1.7-15) months. Most importantly, several novel genetic mutations and pathways were identified. These results offer the opportunity to develop future treatment strategies in this rare cancer."

Clinical • Journal • P2 data • BRCA1

Phase II Study to Evaluate the Efficacy and Safety of TLC388 for Differentiated Neuroendocrine Carcinomas Patients (clinicaltrials.gov) - P2; N=23; Completed; Sponsor: National Health Research Institutes, Taiwan; Not yet recruiting ➔ Completed; N=44 ➔ 23; Trial completion date: Dec 2020 ➔ Dec 2018; Trial primary completion date: Dec 2018 ➔ Apr 2018

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2; N=29; Terminated; Sponsor: Taiwan Liposome Company; Completed ➔ Terminated; Current study design couldn't support futher development on this indication

Clinical • Trial termination