On October 12, 2022 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage biopharmaceutical company focused on developing and commercializing precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported that preclinical combination data of KRAS inhibitors and nab-sirolimus will be presented during a poster session at the upcoming 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, taking place October 26-28, 2022 in Barcelona, Spain (Press release, Aadi Bioscience, OCT 12, 2022, View Source [SID1234621976]). Nab-sirolimus is a novel albumin-bound nanoparticle form of the mTOR inhibitor sirolimus and is approved for the treatment of locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).
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!
KRAS is frequently mutated in non-small cell lung cancer (NSCLC) and other tumor types, with the KRAS G12C present in approximately 9% of NSCLC patients. The mTOR pathway is often activated in patients with the KRAS mutation and contributes to adaptive resistance to KRAS inhibitors. Aadi scientists conducted studies to determine the utility of a combination of the mTOR inhibitor nab-sirolimus and KRAS inhibitors, which could have synergistic potential in the treatment of KRAS mutated cancers.
Sotorasib (AMG510) is approved for the treatment of KRAS G12C-mutated locally advanced or metastatic NSCLC, and adagrasib (MRTX 849) is under review for the treatment of KRAS G12C-mutated NSCLC. This study investigated the antitumor activity of mTOR inhibitors nab-sirolimus or everolimus in combination with sotorasib or adagrasib in KRAS G12C-mutated cancer xenografts.
Results of these studies showed that combining nab-sirolimus with either of the KRAS G12C inhibitors significantly improved response against KRAS G12C mutant lung cancer and bladder cancer tumors in vivo and nab-sirolimus also showed significantly greater potency in the combination compared to everolimus. The nab-sirolimus combinations with sotorasib and adagrasib will be detailed in the upcoming poster.
"Increase in mTOR signaling can cause resistance to KRAS G12C inhibitors. Combination strategies that act through disease-driving pathways, like mTOR and KRAS, are critical to mitigating resistance and providing clinical benefit," said Neil Desai, Ph.D., Founder and Chief Executive Officer of Aadi Bioscience. "These preclinical results demonstrate that nab-sirolimus has the potential to be the preferred mTOR inhibitor in combination with the KRAS inhibitors and we look forward to exploring this approach in the clinic."
The details of the poster presentation are below:
Title: "KRAS G12C mutated NSCLC and bladder cancer xenografts treated with sotorasib and adagrasib in combination with mTOR inhibitors show improved antitumor activity of nab-sirolimus vs everolimus"
Abstract Number: 163
Session Title/Code: Combination Therapies/PP08
Date/Time: Thursday, October 27, 2022, 10am – 5pm
Authors: Shihe Hou, PhD, Jorge Nieva, MD, and Neil Desai, PhD