liposomal topotecan (FF-10850) / Fujifilm Holdings - LARVOL DELTA

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Merkel Cell Carcinoma (clinicaltrials.gov) - P1 | N=96 | Active, not recruiting | Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cervical Cancer • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Sarcoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Merkel Cell Carcinoma (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc. | Trial primary completion date: Mar 2025 ➔ Dec 2025

Metastases • Trial primary completion date • Cervical Cancer • Endocrine Cancer • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Sarcoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc. | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2024 ➔ Mar 2025

Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Endocrine Cancer • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Sarcoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor

Quantification of Unencapsulated Drug in Target Tissues Demonstrates Pharmacological Properties and Therapeutic Effects of Liposomal Topotecan (FF-10850). (PubMed, Pharm Res) - "Tissue pharmacokinetics of unencapsulated topotecan elucidated the favorable pharmacological properties of FF-10850. Evaluation of tissue exposure to an unencapsulated drug with appropriate pharmacodynamic markers can be valuable in optimizing liposomal drugs and dosing regimens."

Journal • Hematological Malignancies • Oncology • Ovarian Cancer • Solid Tumor

Orphan Designation: Treatment of Merkel Cell Carcinoma (FDA) - Date Designated: 03/21/2024

Orphan drug • Merkel Cell Carcinoma

ProGenier signs a material transfer agreement with FUJIFILM Pharmaceuticals in the U.S. [Google translation] (Medifonews) - "Progenier...signed a Material Transfer Agreement with FUJIFILM Pharmaceuticals USA Inc...Fujifilm's global center for new drug development, to explore the synergy effects of the materials of both companies. announced that it had signed a contract...Under this contract, Progenier will receive FF-10832 and FF-10850, liposomal chemotherapy drugs in clinical trials from FFPU, and explore the effects of combination with ProLNG-001, an immunomodulator that Progenier is developing....ProLNG-001 was developed as an existing vaccine adjuvant, but when injected with an in-situ vaccine, that is, a treatment that induces cell death, in a non-clinical tumor model, it showed high efficacy and was also confirmed to have an immunity acquisition effect, so it will be scheduled for clinical trial 1 in 2025."

Licensing / partnership • New P1 trial • Preclinical • Biliary Tract Cancer • Bladder Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Solid Tumor

FF-10850, a Novel Liposomal Topotecan Achieves Superior Anti-tumor Activity via Macrophage- and Ammonia-mediated Payload Release in the Tumor Microenvironment. (PubMed, Mol Cancer Ther) - P1 | "FF-10850 significantly enhanced anti-tumor activity in combination with carboplatin or PARP inhibitor without detrimental effects on body weight in murine xenograft models, and demonstrated synergistic anti-tumor activity combined with anti-PD-1 antibody with the development of tumor antigen-specific immunity. These results support phase Ⅰ investigation of FF-10850 for the treatment of solid tumors including ovarian cancer (NCT04047251), and further evaluation in combination settings."

Biomarker • Journal • Tumor microenvironment • Hematological Disorders • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc. | Trial primary completion date: Jul 2023 ➔ Jul 2024

Metastases • Trial primary completion date • Cervical Cancer • Endocrine Cancer • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Sarcoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor

pH-sensitive liposomes bearing a chemotherapeutic agent and a natural apoptosis modulator for effective intracellular delivery to the solid tumor. (PubMed, Drug Deliv Transl Res) - "Topotecan (TPT) and capsaicin were used for the treatment of solid tumors...The HA-pSLPs formulation has shown remarkable tumor regression as compared to PpSLPs, pSLPs, and free drug combinations. These results demonstrated that TPT- and CAP-loaded HA-pSLPs offer a potential platform for targeted drug delivery to solid tumors."

Journal • Oncology • Solid Tumor

FF-10850, a dihydrosphingomyelin (DHSM)-based novel liposomal topotecan, achieved favorable efficacy and safety in combination with platinum, PARP and immune checkpoint inhibitors (AACR 2023) - P1 | "Although topotecan is also approved in combination with cisplatin for cervical cancer, reductions of dose and administration frequency are required due to safety issues. FF-10850 demonstrated favorable efficacy and safety in combination with carboplatin, olaparib or anti-PD-1 antibody, likely related to preferential tumor drug exposure. The combination of FF-10850 with anti-PD-1 antibody efficiently established tumor-specific immunity and long-lasting tumor suppression. Collectively, these observations strongly support further investigations of FF-10850 and improved efficacy in combination with various anti-cancer agents."

Checkpoint inhibition • Clinical • Combination therapy • Cervical Cancer • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • BRCA2

A first-in-human phase 1 dose escalation study of FF-10850 (liposomal topotecan) in patients with advanced solid tumors. (ASCO 2022) - P1 | "FF-10850 was well-tolerated up to 2 mg/m2 with anti-tumor activity demonstrated in heavily pre-treated pts with solid tumors including ovarian cancer, and an improved PK profile allowing less frequent dosing compared to topotecan. Expansion is ongoing in pts with ovarian and Merkel cell carcinoma at the RP2D of 2 mg/m2 IV on Day 1 & 15 of a 28-day cycle."

Clinical • P1 data • Alopecia • Anemia • Fatigue • Hematological Disorders • Merkel Cell Carcinoma • Neuroendocrine Tumor • Neutropenia • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia

F7 and topotecan co-loaded thermosensitive liposome as a nano-drug delivery system for tumor hyperthermia. (PubMed, Drug Deliv) - "Then therapeutic efficacy revealed synergism of TPT and F7 co-loaded in TSL, together with hyperthermia. Therefore, the F7-TPT-TSL may serve as a promising system for temperature triggered cancer treatment."

Journal • Oncology • TOP1

[VIRTUAL] Novel liposomal topotecan formulation has a lower IC50 than the free form on neuroblastoma cells (AACR-II 2020) - "In pilot studies, we found that microbubbles containing liposomal doxorubicin, an agent that is effective against NB, and focused ultrasound (sonoporation) increased doxorubicin uptake in NB xenografts. 2T-T had a mean IC50 of 0.37±0.58uM(mean R2=0.9±0.07).Empty liposomes caused no cytotoxicity in any cell line. We found no difference in IC50 according to S or N type (0.50±0.65vs 0.35±0.58(p=ns)). The mean IC50 of MYCN-amplified cells was 0.47±0.63,while that of non-MYCN-amplified was 0.031±0.029(n=2), suggesting no difference in cytotoxicity based on MYCN status."

Neuroblastoma • Oncology • Solid Tumor • MYCN

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=96; Recruiting; Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.; Not yet recruiting ➔ Recruiting

Enrollment open

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=96; Not yet recruiting; Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

New P1 trial

FF-10850, a novel liposomal topotecan, achieved superior anti-tumor effects and a favorable safety profile via preferential distribution followed by dual payload release mechanisms in tumor (AACR 2019) - "Introduction:FF-10850, a novel liposomal topotecan, has shown superior anti-tumor effects and a favorable safety profile compared with topotecan or doxorubicin HCl liposome injection (lipo-dox). An additional mechanism is mediated by ammonia, which is reported to be a metabolite in glutaminolysis activated by the metabolic shift in tumor cells. These characteristics of FF-10850 distribution and release may translate to enhanced anti-tumor effects of FF-10850 as observed in subcutaneous as well as intraperitoneally disseminated tumor models closely resembling clinical conditions."

Clinical