FF-10502 / Fujifilm Holdings - LARVOL DELTA

A phase 1/2a safety, pharmacokinetics, and efficacy study of the novel nucleoside analog FF-10502-01 for the treatment of advanced solid tumors. (PubMed, Cancer) - "FF-10502-01 was well tolerated with manageable side effects and limited hematologic toxicity. Durable PRs and disease stabilizations were observed in heavily pretreated biliary tract patients who had received prior gemcitabine. FF-10502-01 is distinct from gemcitabine and may represent an effective therapy."

Journal • Metastases • P1/2 data • PK/PD data • Biliary Cancer • Cholangiocarcinoma • Dermatology • Fatigue • Gallbladder Cancer • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Hypotension • Neutropenia • Oncology • Pancreatic Cancer • Pruritus • Solid Tumor • Thrombocytopenia • BAP1 • PBRM1

First-in-human phase 1 trial of pyrimidine anti-metabolite FF-10502-01 in patients with advanced cancer (AACR 2017) - "...In gem-resistant pancreatic PDX models, FF-10502-01, alone and in combination with nab-paclitaxel (nab-pac), had higher efficacy and tolerability than gem/gem+nab-pac...11 pts were male and 11 female, median age 63 years (range 21-80), average number of prior cytotoxic therapies 3 (range 1-7) and 9 pts with prior gemcitabine therapy. Common related adverse events were Gr 1/2 nausea (43%), rash (38%), fever (29%), fatigue (19%), and vomiting despite prophylactic ondansetron and dexamethasone (14%)... The pyrimidine nucleoside antimetabolite FF-10502-01 is well tolerated with prophylactic anti-emetics and demonstrated preliminary antitumor activity in heavily pretreated patients."

P1 data • Biliary Cancer • Biosimilar • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Ovarian Cancer • Sarcoma • Venous Thromboembolism

Phase 1/2 trial of FF-10502-01, a pyrimidine antimetabolite, in patients with advanced cholangiocarcinoma and solid tumors. (ASCO 2019) - P1/2; "Background: FF10502 is a synthetic pyrimidine nucleoside similar to gemcitabine (gem) with a sulfur in the pentose ring...1 pt with prior rituximab for ITP developed PML... FF10502 is well tolerated in pts with advanced cancers refractory to standard therapies. Early signals of efficacy warranting further exploration were seen in heavily pretreated cholangiocarcinoma pts (median: 4 prior therapies). Patient selection based on differential effects of FF10502 on DNA polymerases will be explored."

Clinical • P1/2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Urothelial Cancer

Study of FF-10502-01 in Patients With Advanced Solid Tumors and Lymphomas (clinicaltrials.gov) - P1/2; N=99; Completed; Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.; Active, not recruiting ➔ Completed; Trial completion date: Jun 2021 ➔ Nov 2020; Trial primary completion date: May 2021 ➔ Nov 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • MRI

Study of FF-10502-01 in Patients With Advanced Solid Tumors and Lymphomas (clinicaltrials.gov) - P1/2; N=99; Active, not recruiting; Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.; Trial completion date: Mar 2021 ➔ Jun 2021; Trial primary completion date: Dec 2020 ➔ May 2021

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • MRI

A novel antimetabolite, FF-10502-01 exhibits potent antitumor activity via inhibition of both DNA replication and DNA damage repair in solid tumor cells (AACR 2018) - "Introduction FF10502-01 is a synthetic pyrimidine nucleoside analogue that is structurally similar to gemcitabine (GEM) with a substitution of sulfur for oxygen in the pentose ring...On the other hand, only FF-10502-01 showed potent cytotoxic activity against serum starvation-induced dormant SUIT-2 cells in combination with DNA damage inducers (DDIs: H2O2, cisplatin, or temozolomide)...In vitro enzymatic assays showed that FF-10502-01 was far more potent than GEM in inhibiting DNA polymerase-beta, which plays an essential role in repairing oxidative DNA damage via the base-excision repair pathway. The inhibitory activity of DNA repair may explain the differential effect of FF-10502-01 in solid tumors in which reactive oxygen species are generated by tumor specific microenvironment.Conclusions Unlike GEM, FF-10502 is unique in preventing DNA repair via polymerase-beta inhibition when combined with DDIs, suggesting a dual MOA for FF-10502 in solid tumors compared to GEM."

Biliary Cancer • Cholangiocarcinoma • Ovarian Cancer • Pancreatic Cancer

Study of FF-10502-01 in Patients With Advanced Solid Tumors and Lymphomas (clinicaltrials.gov) - P1/2; N=99; Active, not recruiting; Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • MRI

FF-10502, an antimetabolite with novel activity on dormant cells, is superior to gemcitabine for targeting pancreatic cancer cells. (PubMed, J Pharmacol Exp Ther) - "In vitro serum starvation-induced dormant SUIT-2 cells developed resistance to gemcitabine even in combination with DNA damage inducers (DDIs; HO, cisplatin, and temozolomide). FF-10502 was far more potent than gemcitabine in inhibiting DNA polymerase β, which may explain the difference in dormant cell injury, although further investigations for direct evidences are necessary. In conclusion, our study demonstrated the beneficial antitumor effects of FF-10502 in clinically relevant in vivo models, and suggests the importance of preventing DNA repair unlike gemcitabine."

Journal

Study of FF-10502-01 in Patients With Advanced Solid Tumors and Lymphomas (clinicaltrials.gov) - P1/2; N=84; Recruiting; Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.; Trial completion date: Mar 2019 ➔ Mar 2021; Trial primary completion date: Dec 2018 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date