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Poster presentation scheduled for
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
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
Authors: Shihe Hou, PhD,
Aadi is a commercial-stage biopharmaceutical company focused on precision therapies for genetically defined cancers to bring transformational therapies to cancer patients with mTOR pathway driver alterations. Aadi received FDA approval in November of 2021 and in February of 2022 commercialized FYARRO® for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).
Aadi has also initiated PRECISION 1, a Phase 2 tumor-agnostic registration-intended trial in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. More information on the Company's development pipeline is available on the Aadi website at www.aadibio.com and connect with us on Twitter and LinkedIn.
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