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TP009/#1495  A phase 2, open-label, single-arm, prospective, multi-center study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer
  1. Lauren Dockery1,
  2. Anna Priebe2,
  3. Linda Duska3,
  4. Angela Green4,
  5. Cara Mathews5,
  6. Fernanda Musa6,
  7. David O’Malley7,
  8. Allison Puechl8,
  9. Li Ding9,
  10. Anita Schmid10,
  11. Willis Navarro11,
  12. Brian Slomovitz12 and
  13. Kathleen Moore1
  1. 1Stephenson Cancer Center, Oklahoma University Health, Gynecologic Oncology, Oklahoma City, USA
  2. 2Texas Oncology, -, Tyler, USA
  3. 3University of Virginia, -, Charlottesville, USA
  4. 4Memorial Sloan Kettering Cancer Center, -, New York, USA
  5. 5Women and Infants Hospital, -, Providence, USA
  6. 6Swedish Cancer Institute, -, Seattle, USA
  7. 7The Ohio State Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Columbus, USA
  8. 8Atrium Health Levine Cancer Institute, Gynecologic Cancer, Charlotte, USA
  9. 9Aadi Bioscience, Biostatistics, Programming and Data Management, Pacific Palisades, USA
  10. 10Aadi Bioscience, Clinical Science, Pacific Palisades, USA
  11. 11Aadi Bioscience, Clinical Development and Pharmacovigilance, Pacific Palisades, USA
  12. 12Mount Sinai Medical Center, Gynecologic Oncology, Miami Beach, USA


Introduction Despite recent pivotal data demonstrating improved outcomes with immunotherapy plus chemotherapy, regardless of mismatch repair status, alternative treatment options for advanced or recurrent endometrial carcinoma (EC) remain necessary. Dysregulation of mTOR signaling is implicated in the pathology of EC, particularly in endometrioid EC (EEC) in which >80% harbor PTEN or PI3K/AKT/mTOR pathway alterations. Moreover, crosstalk between mTOR and estrogen receptor signaling pathways is associated with endocrine resistance. GOG-3007 and other phase 2 studies have demonstrated that the combination of conventional mTOR inhibitors (mTORi) and endocrine therapy provides clinical benefit in patients with EC. nab-Sirolimus is a nanoparticle injectable form of mTORi approved for malignant perivascular epithelioid cell tumor. Preclinical data with nab-sirolimus demonstrated improved tumor accumulation, mTOR inhibition, and tumor growth suppression compared with conventional mTORi. We hypothesize that nab-sirolimus in combination with letrozole may produce synergistic antitumor activity in patients with recurrent EEC.

Methods In this phase 2, open-label, single-arm, multi-center study (NCT05997017), nab-sirolimus (100 mg/m2, IV, days 1 and 8 of each 21-day cycle) and letrozole (2.5 mg, oral, daily) are administered to patients (~29 planned) with clinically confirmed, advanced or recurrent EEC. Eligibility criteria include age ≥18 years, 0–1 prior chemo-based regimens, ECOG 0–1, mTORi naïve, and RECIST-measurable disease. The primary endpoint is best ORR by RECIST v1.1; key secondary endpoints include duration of response, PFS, OS, and safety. The relationship between biomarkers and response outcomes is an exploratory endpoint.

Current Trial Status Open for enrollment.

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