HTI-1090 / Jiangsu Hengrui Pharma - LARVOL DELTA

IDO and TDO inhibitors in cancer immunotherapy: mechanisms, clinical development, and future directions. (PubMed, Front Pharmacol) - P1 | "Among these, medications like Indoximod, Epacadostat, and Navoximod have shown promise in influencing the immune system and slowing tumor progression, while dual inhibitors like HTI-1090 try to address broader metabolic connections. The use of IDO/TDO inhibitors with conventional anticancer medications demonstrates their potential to reshape cancer treatment paradigms, contingent on further research to optimize efficacy and safety. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT03844438."

Journal • Review • Oncology • TDO2

Preclinical PK investigation of a novel IDO1/TDO dual inhibitor-SHR9146 in mouse plasma and tissues by LC-MS/MS. (PubMed, Front Oncol) - "The results showed that SHR9146 had dose-independent kinetics in mice via oral administration and was absorbed rapidly and distributed widely. The study provides a good basis for further drug development assessment."

Journal • Preclinical • IDO1

Preclinical PK investigation of a novel IDO1/TDO dual inhibitor-SHR9146 in mouse plasma and tissues by LC-MS/MS (Front Oncol) - "SHR9146 was stable in all the tested bio-samples with recoveries >90%. Pharmacokinetic parameters were obtained by non-compartmental analysis. SHR9146 has a half-life of 0.713 h when IV-injected, with CL 12 mL/min/kg and Vd 0.666 L/kg. After oral dosing from 20 to 80 mg/kg, Cmax (range from 8.751 to 12.893 μg/mL) and AUC0-t (range from 15.606 to 69.971 μg·h/mL) of SHR9146 showed dose proportionality....In addition, SHR9146 was found to be absorbed rapidly and distributed widely and mainly in the stomach, adrenal gland, liver, and lung."

PK/PD data • Preclinical • Oncology

Pre-clinical PK investigation of a novel IDO1/TDO dual inhibitor - SHR9146 in mice plasma and tissues by LC-MS/MS (Front Oncol) - "SHR9146 was stable in all the tested bio-samples with recoveries >90%. Pharmacokinetic parameters were obtained using non-compartmental analysis. SHR9146 has a half-life of 0.713 h when IV-injected, with CL 12mL/min/kg and Vd 0.666L/kg. After oral dosing from 20 to 80 mg/kg, Cmax (range from 8.751 to 12.893 μg/mL) and AUC0-t (range from 15.606 to 69.971 μg·h/mL) of SHR9146 showed dose proportionality. Other post oral pharmacokinetic parameters in plasma were as follows (n=6): Tmax 0.79 ± 0.36 h, t1/2 1.586 ± 0.853 h, CL 19.8 ± 0.9 mL/min/kg, Vd 3.427± 1.617 L/kg, and the absolute bioavailability of 54.2%  12.6% (range from 40.2% to 64.7%)."

PK/PD data • Preclinical • Oncology • Solid Tumor

PIANO: Phase I Study of SHR9146 + SHR-1210 +/- Apatinib in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Unknown status ➔ Active, not recruiting | N=200 ➔ 23 | Trial completion date: May 2020 ➔ Sep 2023 | Trial primary completion date: May 2019 ➔ Jun 2023

Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Immune Modulation • Oncology • Solid Tumor

[VIRTUAL] A phase I study of an IDO inhibitor (SHR9146) plus camrelizumab and in combination with/without apatinib in patients with advanced solid tumors: Safety and efficacy analysis. (ASCO 2021) - P1 | "SHR9146 plus camrelizumab in combination with/without apatinib demonstrated promising anti-tumor activity with acceptable safety in pts with advanced solid tumors . Further study is needed to validate the efficacy and safety."

Clinical • Combination therapy • P1 data • Cervical Cancer • Fatigue • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Kidney Cancer • Liver Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor

A Trial of HTI-1090 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: Atridia Pty Ltd.; Trial completion date: Jul 2019 ➔ Jan 2019

Clinical • Trial completion date

A Trial of HTI-1090 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: Atridia Pty Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Trial of HTI-1090 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: Atridia Pty Ltd.; Trial completion date: Apr 2019 ➔ Jul 2019

Clinical • Trial completion date