Aadi Bioscience Reveals Tumor-Targeting Data for nab-Sirolimus at ASCO Meeting
Aadi Bioscience, Inc., a precision oncology company, has unveiled new nonclinical data demonstrating that nab-sirolimus shows significantly higher intratumoral drug concentrations, stronger inhibition of mTOR targets, and greater antitumor activity compared to intravenous (IV) and oral mTOR inhibitors in a xenograft model. These findings will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting from May 31 to June 4, 2024.
Loretta Itri, MD, Chief Medical Officer at Aadi, stated that the company aims to enhance the effectiveness of mTOR inhibition by combining nanoparticle albumin-bound (nab) technology with sirolimus. This combination enhances drug delivery, stability, solubility, and targeting. The promising results suggest that nab-sirolimus may surpass the limitations of current mTOR therapies delivered orally or intravenously, offering potential benefits in treating hard-to-manage cancers.
Key highlights from the research abstract include:
Title: Antitumor activity of nab-sirolimus versus mTOR inhibitors temsirolimus, sirolimus, and everolimus in A549 NSCLC xenografts
Lead Author: Shihe Hou
Abstract:
Despite the critical role of the mTORC1 pathway in cancer cell growth and survival, mTOR inhibitors like temsirolimus, sirolimus, and everolimus have shown limited clinical effectiveness. In A549 xenografts, nab-sirolimus significantly suppressed tumor growth compared to IV temsirolimus and oral sirolimus and everolimus. Drug concentration in tumors 24 hours post-IV mTOR inhibitor treatment was markedly higher with nab-sirolimus (420-539 ng/g) than temsirolimus (34.9 ng/g) and its active metabolite (13.2 ng/g). Tumor uptake of nab-sirolimus also far exceeded that of sirolimus and everolimus at steady-state. These results advocate for further clinical evaluation of nab-sirolimus, either as a standalone treatment or in combination with other therapies.
In addition, Aadi will present a trials-in-progress poster on its Phase 2 study of nab-sirolimus paired with letrozole in treating advanced or recurrent endometrioid-type endometrial cancer (EEC), a challenging mTOR-driven cancer. Endometrial cancer is the most prevalent cancer of female reproductive organs and one of the few cancers with rising mortality rates, with around 10,000 new EEC cases diagnosed annually.
Poster details and key points include:
Title: A phase 2, open-label, single-arm, prospective, multicenter study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer
Presenting Author: Lauren Dockery, MD, MS
Session Title: Poster Session – Gynecologic Cancer
Abstract Number: TPS5640
Date/Time: Monday, June 3rd, 9:00 am – 12:00 pm
This Phase 2 open-label, multicenter study aims to assess the efficacy and safety of nab-sirolimus and letrozole in patients with advanced or recurrent EEC. The combination is studied for its potential to offer additive anti-tumor activity in this patient group. EEC is significantly associated with dysregulated mTOR signaling, with over 80% of cases showing PTEN or PI3K/AKT/mTOR pathway alterations. Prior clinical trials with mTOR inhibitors and letrozole in endometrial cancer patients have shown encouraging outcomes. Despite recent advancements with immunotherapy and chemotherapy, alternative treatment options are still critically needed for advanced or recurrent EEC patients.
Aadi Bioscience is committed to developing and commercializing therapies targeting cancers with mTOR pathway alterations. By combining nab technology with sirolimus, Aadi aims to optimize the potential of mTOR inhibition. The company has received FDA approval for FYARRO® to treat adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumors (PEComa). Aadi is also investigating nab-sirolimus in various Phase 2 trials for challenging mTOR-driven cancers, including neuroendocrine tumors and advanced or recurrent endometrioid-type endometrial cancer.
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