Phase 2 Trial of Nab-Sirolimus in Solid Tumors Stops Due to Futility

Tumor cell being attacked - Generated with Google Gemini AI

The phase 2 PRECISION1 trial (NCT05103358) evaluating nab-sirolimus (Fyarro) in patients with solid tumors harboring TSC1 or TSC2 inactivating alterations will be halted.¹

An independent data monitoring committee deemed that the study was unlikely to meet the required efficacy threshold to support accelerated approval, the goal of this study.

"We are humbled by the effort of the investigators, support staff, and most importantly, the patients and their families who took part in PRECISION1. While nab-sirolimus showed monotherapy activity in the study population, the trial fell short of delivering what we believe would be required to support an accelerated approval in the broad TSC1/TSC2 inactivating mutations indication. We look forward to providing the full trial analysis at a later date," said David Lennon, president and chief executive officer of Aadi Bioscience, in a press release.

The company will continue to focus on the nab-sirolimus for its approved indication, perivascular epithelioid sarcoma (PEComa). The FDA approved the agent in PEComa in November 2021, based on findings from the phase 2 AMPECT study (NCT02494570).

Additionally, 2 ongoing phase 2 trials evaluating nab-sirolimus will stop enrolling new patients but continue dosing enrolled patients with advanced or recurrent endometrioid-type endometrial cancer (EEC; NCT05997017) and neuroendocrine tumors (NETs; NCT05997056).

About the Phase 2 Study of Nab-Sirolimus in Endometrial Cancer

Twenty patients across 9 locations in the US have been enrolled in the phase 2 study investigating nab-sirolimus plus letrozole for the treatment of EEC.2 The study’s primary end point is overall response rate (ORR), and secondary end points include duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs).

To be eligible for enrollment, patients must have metastatic or locally advanced EEC where surgical resection was not an option or likely to result in severe morbidity. Additionally, patients had to have an ECOG performance status of 0 or 1, adequate liver function, adequate renal function, and adequate hematologic parameters.

The study has an estimated completion date of October 2026.

About the Phase 2 Study of Nab-Sirolimus in Neuroendocrine Tumors

Ten patients with well-differentiated NETs of the gastrointestinal tract, lung, or pancreas who have not received prior mTOR inhibitors have been enrolled in this phase 2 study.3 The study’s primary end point is ORR, and secondary end points include incidence and severity of AEs, DOR, DCR, TTR, PFS, and OS.

To be eligible for enrollment, patients were required to have functional or nonfunctional, locally advanced unresectable or metastatic NETs and have received 2 or less prior lines of therapy, excluding somatostatin analogs. Additionally, patients must have had an ECOG performance status of 0 or 1, adequate liver function, adequate renal function, and adequate hematologic parameters.

The study’s estimated completion date is December 8, 2025.

REFERENCES:

1. Aadi Bioscience provides PRECISION1 trial and corporate updates. News release. Aadi Bioscience, Inc. August 20, 2024. Accessed August 22, 2024. https://tinyurl.com/2vy9rp7x

2. Trial of nab-sirolimus in combination with letrozole in patients with advanced or recurrent endometrioid endometrial cancer. ClinicalTrials.gov. Updated May 21, 2024. Accessed August 22, 2024. https://www.clinicaltrials.gov/study/NCT05997017

3. Trial of nab-sirolimus in patients with well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract, lung, or pancreas who have not received prior treatment with mTOR inhibitors. ClinicalTrials.gov. Updated July 16, 2024. Accessed August 22, 2024. https://www.clinicaltrials.gov/study/NCT05997056