S81694 / Nerviano Medical Sciences, Servier - LARVOL DELTA

First-in-man, first-in-class phase I study with the monopolar spindle 1 kinase inhibitor S81694 administered intravenously in adult patients with advanced, metastatic solid tumours. (PubMed, Eur J Cancer) - "S81694 can be administered safely as a single agent in adults with solid tumours on days 1,8,15 of a 28-day cycle up to a dose of 135 mg/m/week without reaching MTD. The RP2D was not defined due to the prioritization of the use of S81694 in combination with cytotoxic agents, based on emerging preclinical data."

Journal • P1 data • Fatigue • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Disorders • Hepatocellular Cancer • Hypertension • Neutropenia • Oncology • Renal Cell Carcinoma • Solid Tumor

[VIRTUAL] The MPS1 inhibitor S81694 is active in acute myeloid leukemia (AML) (AACR-II 2020) - "The MPS1i S81694 shows significant preclinical activity in vitro and in vivo in AML. Combinations with different drugs active in AML are ongoing."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCL2L1 • CASP3 • CCNB1 • MCL1 • MPS1

Resistant epileptic encephalopathy in a child with microcephalic capillary malformation syndrome (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "The boy was diagnosed with a previously described variant of the nucleotide sequence in exon 2 of the STAMBP chr2 gene:74058171rs781694797 188A>G in the homozygous state, leading to the replacement of the amino acid p.Tyr63Cys in 63 protein position...This variant is considered as pathogenic, related to the patient's phenotype. The article presents a literature review of this syndrome and the case report."

Clinical • Journal • CNS Disorders • Epilepsy

S 81694 Plus Paclitaxel in Metastatic Breast Cancer (clinicaltrials.gov) - P1/2; N=22; Completed; Sponsor: Institut de Recherches Internationales Servier; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Polymorphisms in NR5A2, gene encoding Liver Receptor Homolog-1 are associated with Preterm Birth. (PubMed, Pediatr Res) - "This study suggests a potential association between intronic SNPs in the NR5A2 gene and PTB. NR5A2 gene encodes for the liver receptor homolog-1 protein, which plays a critical role in regulation of cholesterol metabolism, steroidogenesis, and progesterone synthesis. These findings suggest that NR5A2 may be important in the pathophysiology of PTB and exploring noncoding regulators of NR5A2 is warranted."

Journal • Biosimilar

S 81694 Plus Paclitaxel in Metastatic Breast Cancer (clinicaltrials.gov) - P1/2; N=22; Active, not recruiting; Sponsor: Institut de Recherches Internationales Servier; Recruiting ➔ Active, not recruiting; N=117 ➔ 22; Trial completion date: Mar 2023 ➔ Mar 2020; Trial primary completion date: Mar 2023 ➔ Mar 2020

Clinical • Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

Preclinical Activity of the MPS1 Inhibitor S81694 in Acute Lymphoblastic Leukemia (ALL) (ASH 2019) - "A small molecule Mps1i (S81694) was tested alone (0 to 1000nM) or in combination with imatinib, dasatinib, nilotinib and ponatinib in BCR-ABL1+ ALL cell lines. Mps1i S81694 yields significant preclinical activity in T-and B-cell ALL including BCR-ABL1+ models. Interestingly S81694 was efficacious in a TKI resistant cell line."

Preclinical • ABL1 • MPS1

Servier showcases robust presence at ASH 2019 (PRNewswire) - "Servier Group and Servier Pharmaceuticals, the U.S. subsidiary of the global French pharmaceutical company, today announced that data from multiple studies will be presented at the 61st Annual Meeting of the American Society of Hematology (ASH) in Orlando, from December 7-10, 2019."

P1 data • Preclinical

Discovery of orally available and potent MPS1(TTK) kinase inhibitors for anti-cancer drugs (AACR 2019) - "...Some of MPS1 inhibitors (NMS-P153, BOS-172722, CFI-402257, BAY-1217389, and BAY-1161909) are in clinical trials. These compounds are treated for solid tumors with or without Paclitaxel...The compounds selectively inhibit MPS1 based on kinase profiling and decrease phosphorylation of MPS1 and Phospho-HH3 signaling, effectively. Some of compounds were selected for further preclinical studies."

S 81694 Plus Paclitaxel in Metastatic Breast Cancer (clinicaltrials.gov) - P1/2; N=117; Recruiting; Sponsor: Institut de Recherches Internationales Servier; Trial completion date: Jun 2022 ➔ Mar 2023; Trial primary completion date: Jun 2021 ➔ Mar 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date