On October 29, 2019 ArQule, Inc. (Nasdaq: ARQL), reported new clinical and preclinical data demonstrating the potential of the company’s AKT inhibitor ARQ 751 in treating solid tumors characterized by mutations in the PI3K/AKT/mTOR pathway (Press release, ArQule, OCT 29, 2019, View Source [SID1234549962]). The findings were detailed in two poster presentations at the 2019 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Traditional tumor biopsies used to identify tumor mutational status can be burdensome for patients; therefore, using biomarkers such as ctDNA from standard blood sampling would be an improved method of identifying mutations and predicting disease response," said Dr. Brian Schwartz, Chief Medical Officer of ArQule.

A poster entitled "The use of biomarkers and ctDNA in a phase 1 trial of ARQ 751" detailed the molecular profiling of a subgroup of patients in the phase 1 clinical trial of ARQ 751 in solid tumor indications characterized by AKT, PIK3CA or PTEN mutations. Key findings suggest that ctDNA could be a valuable measure of patient response to ARQ 751. Specific highlights include:

There is a high concordance (76%) between the pre-study mutation and the mutation as measured using ctDNA profiling
Though patient data are limited, analysis of the correlation between ctDNA mutational status and patient response suggest that PIK3CA H1047R has prognostic value
ARQ 751 exposure correlates with glucose and insulin levels and indicates on-target engagement
A poster entitled "In vitro and in vivo combination of ARQ 751 with PARP inhibitors, CDK4/6 inhibitors, Fulvestrant and Paclitaxel" details preclinical findings from studies of ARQ 751 treatment in combination with a variety of therapeutic agents, in experimental breast cancer models. Overall, data show that the addition of any of the evaluated agents enhances the activity of ARQ 751 in vivo and in vitro and support the therapeutic potential of ARQ 751. Specific highlights include:

The combination of ARQ 751 with an ER antagonist (fulvestrant) or a CDK4/6 inhibitor (palbociclib) or with both agents showed enhanced anti-tumor activity in comparison to the single agents and enhanced pathway inhibition in vivo. A combination of ARQ 751 with both agents showed tumor regression in vivo
The combination of ARQ 751 with chemotherapy (paclitaxel) showed enhanced anti-tumor activity in comparison to single agents in vivo
The combination of ARQ 751 with PARP inhibitors (olaparib, talazoparib, rucaparib) showed enhanced anti-proliferative activity in vitro
A phase 1b clinical study of ARQ 751 in a molecularly defined patient population as single agent or in combination with fulvestrant or paclitaxel is ongoing (NCT02761694).

About ARQ 751
ARQ 751 is orally bioavailable, selective small molecule inhibitor of the AKT serine/threonine kinase. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.